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Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00927186
Collaborator
(none)
69
Enrollment
12
Locations
2
Arms
33
Duration (Months)
5.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate how teriparatide or zoledronic acid affects the bone of postmenopausal osteoporotic women after 6 months of treatment as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis). After completing 12 months of treatment all participants are eligible to participate in an additional 12-month open label extension.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
69 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy
Study Start Date :
Jul 1, 2009
Actual Primary Completion Date :
Oct 1, 2010
Actual Study Completion Date :
Apr 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Teriparatide

Drug: Teriparatide
20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Other Names:
  • LY333334
  • Forteo
  • Forsteo

    		•
    Active Comparator: Zoledronic Acid

    Drug: Zoledronic Acid
    5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.

    Outcome Measures

    Primary Outcome Measures

    1. Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

    Secondary Outcome Measures

    1. Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

    2. Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      MS/BS in EC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

    3. Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Ac.f in CC represents the frequency of activation of new remodeling cycles on BS (bone formation rate [BFR]/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 micrometer (µm)/day or counted as missing.

    4. Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Ac.f in CC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    5. Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Ac.f in EC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    6. Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (cubic millimeter/square millimeter/year [mm³/mm²/year]); calculated as mineral apposition rate (MAR) times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    7. Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    8. Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      BFR in EC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    9. Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive T labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    10. Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    11. Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      MAR in EC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    12. Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    13. Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    14. Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Aj.AR in EC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    15. Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as Osteoid Thickness (O.Th) divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    16. Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    17. Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Mlt in EC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    18. Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    19. Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    20. Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 Months]

      Omt in EC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    21. Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    22. Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    23. Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Tt.FP in EC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    24. Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [6 months]

      a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    25. Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months [24 months]

      a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    26. Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      a. FP in EC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3 day-periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

    27. Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    28. Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    29. Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the endocortical compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    30. Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    31. Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    32. Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the endocortical compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    33. Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    34. Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    35. Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      The length of tetracycline double labels is a measure of the extent of bone formation in the endocortical compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

    36. Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).

    37. Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).

    38. Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

    39. Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

    40. Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Osteoid surface (OS) in the endocortical compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

    41. Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.

    42. Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.

    43. Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Osteoid thickness (OTh.) in the endocortical compartment is a measure of the average thickness of osteoid seams.

    44. Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

    45. Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

    46. Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Wall thickness (WTh.) in the endocortical compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

    47. Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months [6 months]

      Eroded surface/bone surface (ES/BS) in the cancellous compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.

    48. Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months [24 months]

      Eroded surface/bone surface (ES/BS) in the cancellous compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.

    49. Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [6 and 24 months]

      Eroded surface/bone surface (ES/BS) in the endocortical compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.

    50. Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint [Baseline, 1, 3, 6 months]

      CTX is a measure of bone resorption.

    51. Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint [Baseline, 12 months]

      CTX is a measure of bone resorption.

    52. Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint [Baseline, 1, 3, 6 months]

      PINP is a measure of bone formation.

    53. Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint [Baseline, 12 months]

      PINP is a measure of bone formation.

    54. Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint [Baseline, 1, 3, 6 months]

      OC is a measure of osteoblast function.

    55. Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint [Baseline, 12 months]

      OC is a measure of osteoblast function.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years to 89 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Ambulatory, postmenopausal women with osteoporosis (no vaginal bleeding for at least 2 years prior to trial entry)

    • Free of severe or chronically disabling conditions other than osteoporosis that will impair ability to complete the trial

    • Bone mineral density (BMD) T-score of at least -2.5 at the femoral neck, total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture or,

    • Bone mineral density (BMD) T-score of at least -1.5 at the femoral neck, or total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), and either 1 or more atraumatic vertebral fracture(s) or an atraumatic nonvertebral fracture in the opinion of the investigator. Nonvertebral fracture sites allowed are wrist, hip, pelvis, ribs, humerus, clavicle, leg (femur, tibia, and fibula, excluding the ankle).

    • Serum calcium, parathyroid hormone (PTH), alkaline phosphatase must be within normal reference range

    Exclusion Criteria:

    • Have an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton

    • Are allergic or cannot tolerate teriparatide or zoledronic acid or any of their ingredients or components

    • Are allergic to tetracycline

    • Have a history of exposure to tetracycline therapy in the 3 months prior to trial entry

    • Have participated in a prior PTH clinical trial or received prior treatment with teriparatide, PTH, or other related medications

    • Have a vitamin D level below 10 nanogram/milliliter (ng/mL)

    • Have a condition that could possibly put one at risk for an adverse event due to the bone biopsy procedure (e.g. bleeding disorder)

    • Have undergone two previous iliac crest bone biopsies (one in each iliac crest)

    • Have taken any intravenous (IV) osteoporosis medication

    • Have taken other oral osteoporosis medications and have not been off of them for a specific period of time before trial entry

    • Have a history of certain cancers in the 5 years prior to trial entry

    • Have active liver disease

    • Have significantly impaired kidney function

    • Currently have active or suspected diseases that affect the bones, other than osteoporosis

    • Have active or recent history of significant gastrointestinal (stomach or intestinal) disorders

    • Have been treated with certain glucocorticoids for more than 30 days in the past 1 year prior to trial entry

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lakewood Colorado United States 80227
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Atlanta Georgia United States 30319
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Gainesville Georgia United States 30501
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bethesda Maryland United States 20817
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Detroit Michigan United States 48202
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Omaha Nebraska United States 68131
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Albuquerque New Mexico United States 87106
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. West Haverstraw New York United States 10993
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Madison Wisconsin United States 53705
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Calgary Alberta Canada T2N 4Z6
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Vancouver British Columbia Canada V6H 3X8
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Sainte-Foy Quebec Canada G1V 3M7

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00927186
    Other Study ID Numbers:
    • 13032
    • B3D-US-GHDL
    First Posted:
    Jun 24, 2009
    Last Update Posted:
    Apr 4, 2013
    Last Verified:
    Feb 1, 2013
    Keywords provided by Eli Lilly and Company
    osteoporosis
    teriparatide
    zoledronic acid
    histomorphometry
    bone biopsy
    postmenopausal
    Additional relevant MeSH terms:
    Osteoporosis
    Osteoporosis, Postmenopausal
    Zoledronic Acid
    Teriparatide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This was a Phase 4, multicenter, randomized, stratified, double-blind, active comparator-controlled study with the primary endpoint at 6 months. Following the bone biopsy visit at 6 months, the study became open label for an additional 6 months. All participants who complete 12 months of treatment are eligible for an additional 12-month extension.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Period Title: 12 Months Primary Study
    STARTED 34 35
    Completed 6 Months Double Blind Phase 28 31
    COMPLETED 27 31
    NOT COMPLETED 7 4
    Period Title: 12 Months Primary Study
    STARTED 10 11
    COMPLETED 10 11
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Teriparatide Zoledronic Acid Total
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. Total of all reporting groups
    Overall Participants 34 35 69
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.49
    (6.93)
    64.20
    (5.96)
    64.84
    (6.44)
    Sex: Female, Male (Count of Participants)
    Female
    34
    100%
    35
    100%
    69
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Black or African American
    1
    2.9%
    1
    2.9%
    2
    2.9%
    White
    33
    97.1%
    34
    97.1%
    67
    97.1%
    Region of Enrollment (participants) [Number]
    United States
    21
    61.8%
    25
    71.4%
    46
    66.7%
    Canada
    13
    38.2%
    10
    28.6%
    23
    33.3%
    Height (centimeters (cm)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeters (cm)]
    159.28
    (5.92)
    160.00
    (7.38)
    159.64
    (6.66)
    Weight (kilograms (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms (kg)]
    61.25
    (9.21)
    64.75
    (11.66)
    63.03
    (10.60)
    Pulse (beats per minute (bpm)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [beats per minute (bpm)]
    67.41
    (7.15)
    70.60
    (8.79)
    69.03
    (8.13)
    Blood Pressure - Systolic (millimeters of mercury (mmHg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimeters of mercury (mmHg)]
    125.71
    (16.19)
    122.49
    (16.25)
    124.07
    (16.18)
    Blood Pressure - Diastolic (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    74.79
    (8.24)
    73.97
    (10.15)
    74.38
    (9.20)
    Alcohol Use (participants) [Number]
    Yes
    21
    61.8%
    17
    48.6%
    38
    55.1%
    No
    13
    38.2%
    18
    51.4%
    31
    44.9%
    Tobacco Use (participants) [Number]
    Yes
    5
    14.7%
    5
    14.3%
    10
    14.5%
    No
    29
    85.3%
    30
    85.7%
    59
    85.5%
    Caffeine or Xanthine Use (participants) [Number]
    Yes
    29
    85.3%
    30
    85.7%
    59
    85.5%
    No
    5
    14.7%
    5
    14.3%
    10
    14.5%
    Previous Osteoporosis Therapy (participants) [Number]
    Yes
    17
    50%
    21
    60%
    38
    55.1%
    No
    17
    50%
    14
    40%
    31
    44.9%
    Fracture Status (participants) [Number]
    Yes
    14
    41.2%
    17
    48.6%
    31
    44.9%
    No
    20
    58.8%
    18
    51.4%
    38
    55.1%
    Lumbar Spine T-Score (T-Score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-Score]
    -2.79
    (0.83)
    -2.93
    (0.75)
    -2.86
    (0.79)
    Femoral Neck T-Score (T-Score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-Score]
    -2.25
    (0.68)
    -2.29
    (0.74)
    -2.27
    (0.70)
    Total Hip T-Score (T-Score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-Score]
    -1.78
    (0.78)
    -1.88
    (0.91)
    -1.83
    (0.84)
    Serum Procollagen Type I N-Terminal Propeptide (PINP) (microgram/Liter (µg/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [microgram/Liter (µg/L)]
    49.18
    (18.28)
    52.88
    (19.43)
    51.03
    (18.81)
    Serum Carboxyterminal Cross-Linking Telopeptide of Collagen Type I (CTX) (nanogram/milliliter (ng/mL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [nanogram/milliliter (ng/mL)]
    0.43
    (0.23)
    0.42
    (0.19)
    0.43
    (0.21)
    Serum Osteocalcin (microgram/Liter (µg/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [microgram/Liter (µg/L)]
    25.05
    (8.37)
    24.92
    (8.53)
    24.98
    (8.39)

    Outcome Measures

    1. Primary Outcome
    Title Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [percentage of surface]
    5.60
    (10.20)
    0.16
    (2.62)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The pre-specified significance level 0.05 was used.
    Method Wilcoxon (Mann-Whitney)
    Comments
    2. Secondary Outcome
    Title Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [percentage of surface]
    3.00
    0.07
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    3. Secondary Outcome
    Title Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description MS/BS in EC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    6 months (n=23, 29)
    18.64
    0.30
    24 months (n=9, 8)
    5.82
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    4. Secondary Outcome
    Title Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description Ac.f in CC represents the frequency of activation of new remodeling cycles on BS (bone formation rate [BFR]/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 micrometer (µm)/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 28)
    0.37
    0.01
    DL, Imputed SL (ISL) and NL (n=28, 30)
    0.37
    0.01
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    5. Secondary Outcome
    Title Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description Ac.f in CC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    DL and NL (n=9, 6)
    0.19
    0.00
    DL, Imputed SL (ISL) and NL (n=10, 9)
    0.18
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    6. Secondary Outcome
    Title Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Ac.f in EC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    DL and NL at 6 Months (n=23, 20)
    0.83
    0.00
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)
    0.83
    0.01
    DL and NL at 24 Months (n=8, 7)
    0.25
    0.00
    DL, ISL and NL at 24 Months (n=9, 8)
    0.24
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    7. Secondary Outcome
    Title Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (cubic millimeter/square millimeter/year [mm³/mm²/year]); calculated as mineral apposition rate (MAR) times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 28)
    0.0116
    (0.0666)
    0.0002
    (0.0220)
    DL, ISL and NL (n=28, 30)
    0.0116
    0.0002
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    8. Secondary Outcome
    Title Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    DL and NL (n=9, 6)
    0.0057
    0.0000
    DL, Imputed SL (ISL) and NL (n=10, 9)
    0.0057
    0.0001
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    9. Secondary Outcome
    Title Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description BFR in EC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    DL and NL at 6 Months (n=23, 20)
    0.0307
    0.0000
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)
    0.0307
    0.0003
    DL and NL at 24 Months (n=8, 7)
    0.0093
    0.0000
    DL, ISL and NL at 24 Months (n=9, 8)
    0.0090
    0.0000
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    10. Secondary Outcome
    Title Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive T labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 28)
    0.56
    (0.10)
    0.35
    (0.10)
    DL, ISL and NL (n=28, 30)
    0.56
    0.33
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    11. Secondary Outcome
    Title Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    DL and NL (n=9, 6)
    0.44
    0.00
    DL, Imputed SL (ISL) and NL (n=10, 9)
    0.43
    0.30
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    12. Secondary Outcome
    Title Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description MAR in EC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    DL and NL at 6 Months (n=23, 20)
    0.50
    0.00
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)
    0.50
    0.30
    DL and NL at 24 Months (n=8, 7)
    0.43
    0.00
    DL, ISL and NL at 24 Months (n=9, 8)
    0.42
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    13. Secondary Outcome
    Title Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 28)
    0.34
    (0.22)
    0.02
    (0.17)
    DL, ISL and NL (n=28, 30)
    0.34
    0.02
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    14. Secondary Outcome
    Title Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    DL and NL (n=9, 6)
    0.13
    0.00
    DL, Imputed SL (ISL) and NL (n=10, 9)
    0.12
    0.02
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    15. Secondary Outcome
    Title Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Aj.AR in EC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    DL and NL at 6 Months (n=23, 20)
    0.41
    0.00
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)
    0.41
    0.03
    DL and NL at 24 Months (n=8, 7)
    0.35
    0.00
    DL, ISL and NL at 24 Months (n=9, 8)
    0.32
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    16. Secondary Outcome
    Title Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as Osteoid Thickness (O.Th) divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 16)
    13.63
    75.72
    DL, ISL and NL (n=28, 18)
    13.63
    75.72
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    17. Secondary Outcome
    Title Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 5
    DL and NL (n=9, 2)
    38.84
    45.67
    DL, Imputed SL (ISL) and NL (n=10, 5)
    45.33
    128.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.906
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.159
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    18. Secondary Outcome
    Title Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Mlt in EC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 15
    DL and NL at 6 Months (n=23, 6)
    12.63
    26.97
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)
    12.63
    26.70
    DL and NL at 24 Months (n=8, 2)
    15.67
    42.86
    DL, ISL and NL at 24 Months (n=9, 3)
    17.04
    29.03
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.049
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.151
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.196
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    19. Secondary Outcome
    Title Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 16)
    9.99
    9.05
    DL, ISL and NL (n=28, 18)
    9.99
    9.05
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.502
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.597
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    20. Secondary Outcome
    Title Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 5
    DL and NL (n=9, 2)
    13.42
    17.38
    DL, Imputed SL (ISL) and NL (n=10, 5)
    13.52
    13.92
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.077
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.358
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    21. Secondary Outcome
    Title Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Omt in EC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 15
    DL and NL at 6 Months (n=23, 6)
    10.57
    11.27
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)
    10.57
    11.34
    DL and NL at 24 Months (n=8, 2)
    12.30
    14.94
    DL, ISL and NL at 24 Months (n=9, 3)
    13.03
    12.12
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.647
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.120
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.695
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    22. Secondary Outcome
    Title Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 16)
    0.24
    1.46
    DL, ISL and NL (n=28, 18)
    0.24
    1.46
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    23. Secondary Outcome
    Title Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension
    Measure Participants 10 5
    DL and NL (n=9, 2)
    0.60
    0.51
    DL, Imputed SL (ISL) and NL (n=10, 5)
    0.68
    2.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.198
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    24. Secondary Outcome
    Title Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Tt.FP in EC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 15
    DL and NL at 6 Months (n=23, 6)
    0.24
    0.43
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)
    0.24
    0.54
    DL and NL at 24 Months (n=8, 2)
    0.27
    0.62
    DL, ISL and NL at 24 Months (n=9, 3)
    0.31
    0.86
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.151
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.139
    Comments -value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    25. Secondary Outcome
    Title Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
    Description a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    DL and NL (n=28, 16)
    0.15
    0.16
    DL, ISL and NL (n=28, 18)
    0.15
    0.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.154
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.052
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    26. Secondary Outcome
    Title Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
    Description a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 5
    DL and NL (n=9, 2)
    0.19
    0.19
    DL, Imputed SL (ISL) and NL (n=10, 5)
    0.19
    0.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.906
    Comments P-value is for double labels (DL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.159
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL).
    Method Wilcoxon (Mann-Whitney)
    Comments
    27. Secondary Outcome
    Title Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description a. FP in EC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3 day-periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 15
    DL and NL at 6 Months (n=23, 6)
    0.20
    0.20
    DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)
    0.20
    0.28
    DL and NL at 24 Months (n=8, 2)
    0.23
    0.22
    DL, ISL and NL at 24 Months (n=9, 3)
    0.24
    0.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.979
    Comments P-value is for double labels (DL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.695
    Comments P-value is for double labels (DL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.853
    Comments P-value is for double labels (DL), imputed single labels (ISL) and no labels (NL) at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    28. Secondary Outcome
    Title Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    sLS/BS
    3.19
    (2.85)
    0.02
    (1.70)
    dLS/BS
    4.13
    (8.90)
    0.07
    (1.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for sLS/BS.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for dLS/BS.
    Method Wilcoxon (Mann-Whitney)
    Comments
    29. Secondary Outcome
    Title Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the cancellous compartment at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    sLS/BS
    2.25
    0.15
    dLS/BS
    1.69
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments P-value is for sLS/BS.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments P-value is for dLS/BS.
    Method Wilcoxon (Mann-Whitney)
    Comments
    30. Secondary Outcome
    Title Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the endocortical compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the endocortical compartment at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    sLS/BS at 6 months (n=23, 29)
    5.56
    0.25
    dLS/BS at 6 months (n=23, 29)
    13.46
    0.00
    sLS/BS at 24 months (n=9, 8)
    3.75
    0.00
    dLS/BS at 24 months (n=9, 8)
    2.77
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for sLS/BS at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for dLS/BS at 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P-value is for sLS/BS at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments P-value is for dLS/BS at 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    31. Secondary Outcome
    Title Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    No Label
    0
    12
    Single Label Only
    0
    2
    Double Label Only
    0
    3
    Single and Double Label
    28
    13
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is a comparison of "No Label" vs. "Single, Double, Single and Double Label".
    Method Fisher Exact
    Comments
    32. Secondary Outcome
    Title Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy of the cancellous compartment at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    No Label
    0
    4
    Single Label Only
    1
    3
    Double Label Only
    0
    0
    Single and Double Label
    9
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments P-value is a comparison of "No Label" vs. "Single, Double, Single and Double Label".
    Method Fisher Exact
    Comments
    33. Secondary Outcome
    Title Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the endocortical compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy of the endocortical compartment at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    No Label at 6 months (n=23, 29)
    0
    14
    Single Label Only at 6 months (n=23, 29)
    0
    9
    Double Label Only at 6 months (n=23, 29)
    0
    0
    Single and Double Label at 6 months (n=23, 29)
    23
    6
    No Label at 24 months (n=9, 8)
    0
    5
    Single Label Only at 24 months (n=9, 8)
    1
    1
    Double Label Only at 24 months (n=9, 8)
    0
    0
    Single and Double Label at 24 months (n=9, 8)
    8
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is a comparison of "No Label" vs. "Single, Double, Single and Double Label" at 6 months.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments P-value is a comparison of "No Label" vs. "Single, Double, Single and Double Label" at 24 months.
    Method Fisher Exact
    Comments
    34. Secondary Outcome
    Title Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 16
    Median (Inter-Quartile Range) [millimeter (mm)]
    0.35
    (0.08)
    0.24
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    35. Secondary Outcome
    Title Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the cancellous compartment at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 9 2
    Median (Inter-Quartile Range) [millimeter (mm)]
    0.23
    0.29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.906
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    36. Secondary Outcome
    Title Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description The length of tetracycline double labels is a measure of the extent of bone formation in the endocortical compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the endocortical compartment at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 6
    6 months (n=23, 6)
    0.34
    0.30
    24 months (n=8, 2)
    0.27
    0.30
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.536
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.896
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    37. Secondary Outcome
    Title Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [percentage of volume]
    1.32
    (1.47)
    0.24
    (0.76)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    38. Secondary Outcome
    Title Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had OV/BV analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [percentage of volume]
    1.33
    0.18
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    39. Secondary Outcome
    Title Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [percentage of surface]
    11.34
    (8.35)
    2.51
    (4.84)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    40. Secondary Outcome
    Title Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [percentage of surface]
    11.19
    1.26
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    41. Secondary Outcome
    Title Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Osteoid surface (OS) in the endocortical compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    6 months (n=23, 29)
    16.33
    1.87
    24 months (n=9, 8)
    7.48
    1.55
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    42. Secondary Outcome
    Title Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [micrometer (µm)]
    4.92
    (1.38)
    3.77
    (1.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    43. Secondary Outcome
    Title Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [micrometer (µm)]
    5.71
    3.98
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    44. Secondary Outcome
    Title Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Osteoid thickness (OTh.) in the endocortical compartment is a measure of the average thickness of osteoid seams.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    6 months (n=23, 29)
    4.94
    3.70
    24 months (n=9, 8)
    5.23
    3.53
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    45. Secondary Outcome
    Title Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [µm]
    31.29
    (3.25)
    28.63
    (2.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    46. Secondary Outcome
    Title Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [micrometer (µm)]
    31.37
    29.26
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    47. Secondary Outcome
    Title Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Wall thickness (WTh.) in the endocortical compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    6 months (n=23, 29)
    36.30
    32.39
    24 months (n=9, 8)
    34.00
    32.45
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.268
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    48. Secondary Outcome
    Title Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
    Description Eroded surface/bone surface (ES/BS) in the cancellous compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 28 30
    Median (Inter-Quartile Range) [percentage of surface]
    4.59
    2.71
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    49. Secondary Outcome
    Title Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
    Description Eroded surface/bone surface (ES/BS) in the cancellous compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the CC at 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 10 9
    Median (Inter-Quartile Range) [percentage of surface]
    4.44
    2.39
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    50. Secondary Outcome
    Title Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
    Description Eroded surface/bone surface (ES/BS) in the endocortical compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption.
    Time Frame 6 and 24 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the EC at 6 and 24 months.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 23 29
    6 months (n=23, 29)
    4.06
    1.87
    24 months (n=9, 8)
    3.43
    1.88
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments P-value is for 6 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments P-value is for 24 months.
    Method Wilcoxon (Mann-Whitney)
    Comments
    51. Secondary Outcome
    Title Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint
    Description CTX is a measure of bone resorption.
    Time Frame Baseline, 1, 3, 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 34 35
    Change at 1 month (n= 32, 31)
    0.06
    (0.20)
    -0.37
    (0.20)
    Change at 3 months (n= 32, 29)
    0.26
    (0.35)
    -0.35
    (0.19)
    Change at 6 months (n= 25, 28)
    0.31
    (0.48)
    -0.32
    (0.19)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 1 month.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 3 months.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 6 months.
    Method t-test, 2 sided
    Comments
    52. Secondary Outcome
    Title Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint
    Description CTX is a measure of bone resorption.
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug, had baseline and 12 months CTX measurement.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 26 28
    Median (Inter-Quartile Range) [nanogram/milliliter (ng/mL)]
    0.42
    -0.23
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 2 sided
    Comments
    53. Secondary Outcome
    Title Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint
    Description PINP is a measure of bone formation.
    Time Frame Baseline, 1, 3, 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 34 35
    Change at 1 month (n= 32, 31)
    65.50
    (32.03)
    -15.00
    (9.27)
    Change at 3 months (n= 32, 29)
    66.00
    (68.65)
    -39.00
    (14.58)
    Change at 6 months (n= 25, 28)
    84.00
    (135.90)
    -37.50
    (16.44)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 1 month.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 3 months.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 6 months.
    Method t-test, 2 sided
    Comments
    54. Secondary Outcome
    Title Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint
    Description PINP is a measure of bone formation.
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug, had baseline and 12 months PINP measurement.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 26 28
    Median (Inter-Quartile Range) [microgram/liter (µg/L)]
    93.50
    -33.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 2 sided
    Comments
    55. Secondary Outcome
    Title Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint
    Description OC is a measure of osteoblast function.
    Time Frame Baseline, 1, 3, 6 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 34 35
    Change at 1 month (n= 32, 32)
    22.35
    (11.58)
    -3.39
    (2.82)
    Change at 3 months (n=32, 30)
    29.93
    (19.02)
    -12.30
    (5.01)
    Change at 6 months (n= 25, 29)
    30.85
    (33.21)
    -14.06
    (7.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 1 month.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 3 months.
    Method t-test, 2 sided
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is for change from baseline at 6 months.
    Method t-test, 2 sided
    Comments
    56. Secondary Outcome
    Title Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint
    Description OC is a measure of osteoblast function.
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug, had baseline and 12 months OC measurements.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    Measure Participants 26 30
    Median (Inter-Quartile Range) [microgram/liter (µg/L)]
    32.98
    -12.32
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Teriparatide, Zoledronic Acid
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method t-test, 2 sided
    Comments

    Adverse Events

    Time Frame 24 months
    Adverse Event Reporting Description Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.
    Arm/Group Title Teriparatide Zoledronic Acid
    Arm/Group Description 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension. 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
    All Cause Mortality
    Teriparatide Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Teriparatide Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/34 (5.9%) 3/35 (8.6%)
    General disorders
    Non-cardiac chest pain 1/34 (2.9%) 1 0/35 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign salivary gland neoplasm 1/34 (2.9%) 1 0/35 (0%) 0
    Haemangioma of liver 0/34 (0%) 0 1/35 (2.9%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/34 (0%) 0 1/35 (2.9%) 1
    Vascular disorders
    Aneurysm 0/34 (0%) 0 1/35 (2.9%) 1
    Other (Not Including Serious) Adverse Events
    Teriparatide Zoledronic Acid
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 31/34 (91.2%) 31/35 (88.6%)
    Cardiac disorders
    Palpitations 0/34 (0%) 0 2/35 (5.7%) 2
    Gastrointestinal disorders
    Constipation 0/34 (0%) 0 2/35 (5.7%) 2
    Gastrooesophageal reflux disease 2/34 (5.9%) 2 1/35 (2.9%) 1
    Nausea 3/34 (8.8%) 4 4/35 (11.4%) 5
    Vomiting 0/34 (0%) 0 3/35 (8.6%) 3
    General disorders
    Chills 1/34 (2.9%) 1 3/35 (8.6%) 3
    Cyst 0/34 (0%) 0 2/35 (5.7%) 2
    Fatigue 2/34 (5.9%) 2 2/35 (5.7%) 2
    Influenza like illness 0/34 (0%) 0 2/35 (5.7%) 2
    Injection site haemorrhage 0/34 (0%) 0 2/35 (5.7%) 3
    Pain 2/34 (5.9%) 2 4/35 (11.4%) 4
    Pyrexia 1/34 (2.9%) 1 2/35 (5.7%) 2
    Infections and infestations
    Bronchitis 2/34 (5.9%) 2 1/35 (2.9%) 1
    Nasopharyngitis 6/34 (17.6%) 6 4/35 (11.4%) 5
    Sinusitis 2/34 (5.9%) 3 2/35 (5.7%) 2
    Urinary tract infection 1/34 (2.9%) 1 2/35 (5.7%) 2
    Injury, poisoning and procedural complications
    Contusion 1/34 (2.9%) 1 2/35 (5.7%) 2
    Excoriation 2/34 (5.9%) 2 0/35 (0%) 0
    Ligament sprain 2/34 (5.9%) 2 0/35 (0%) 0
    Post procedural haematoma 4/34 (11.8%) 4 4/35 (11.4%) 5
    Procedural pain 8/34 (23.5%) 9 9/35 (25.7%) 10
    Metabolism and nutrition disorders
    Hypercalcaemia 3/34 (8.8%) 4 0/35 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/34 (17.6%) 9 5/35 (14.3%) 5
    Back pain 3/34 (8.8%) 3 7/35 (20%) 7
    Bursitis 1/34 (2.9%) 1 2/35 (5.7%) 3
    Groin pain 1/34 (2.9%) 1 2/35 (5.7%) 3
    Joint swelling 1/34 (2.9%) 1 2/35 (5.7%) 2
    Muscle spasms 5/34 (14.7%) 5 3/35 (8.6%) 5
    Musculoskeletal chest pain 0/34 (0%) 0 2/35 (5.7%) 2
    Myalgia 1/34 (2.9%) 1 2/35 (5.7%) 2
    Neck pain 1/34 (2.9%) 1 3/35 (8.6%) 3
    Osteoarthritis 2/34 (5.9%) 2 2/35 (5.7%) 2
    Pain in extremity 5/34 (14.7%) 5 2/35 (5.7%) 2
    Spinal column stenosis 2/34 (5.9%) 2 0/35 (0%) 0
    Nervous system disorders
    Dizziness 0/34 (0%) 0 3/35 (8.6%) 3
    Headache 4/34 (11.8%) 4 8/35 (22.9%) 9
    Migraine 2/34 (5.9%) 2 1/35 (2.9%) 1
    Sciatica 2/34 (5.9%) 2 1/35 (2.9%) 1
    Psychiatric disorders
    Insomnia 0/34 (0%) 0 2/35 (5.7%) 2
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/34 (0%) 0 2/35 (5.7%) 2
    Cough 2/34 (5.9%) 2 6/35 (17.1%) 6
    Dyspnoea exertional 0/34 (0%) 0 2/35 (5.7%) 2
    Respiratory tract congestion 0/34 (0%) 0 2/35 (5.7%) 2
    Skin and subcutaneous tissue disorders
    Ecchymosis 3/34 (8.8%) 4 1/35 (2.9%) 1
    Erythema 2/34 (5.9%) 2 1/35 (2.9%) 1
    Hyperhidrosis 0/34 (0%) 0 2/35 (5.7%) 2
    Vascular disorders
    Haematoma 4/34 (11.8%) 4 2/35 (5.7%) 2
    Hypertension 0/34 (0%) 0 3/35 (8.6%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00927186
    Other Study ID Numbers:
    • 13032
    • B3D-US-GHDL
    First Posted:
    Jun 24, 2009
    Last Update Posted:
    Apr 4, 2013
    Last Verified:
    Feb 1, 2013