Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01753856
Collaborator
(none)
69
6
2
17
11.5
0.7
Study Details
Study Description
Brief Summary
The purpose of this study is to determine how teriparatide or denosumab affects the bone of postmenopausal women with osteoporosis after 3 months of treatment, as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
69 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Anabolism Versus Antiresorption: A Quadruple Labeling Histomorphometry Study to Compare the Mechanism of Action of Teriparatide and Denosumab in Postmenopausal Women With Osteoporosis
Study Start Date
:
Jan 1, 2013
Actual Primary Completion Date
:
Jun 1, 2014
Actual Study Completion Date
:
Jun 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Teriparatide 20 micrograms (µg) teriparatide administered subcutaneously (SC) once every day for 6 months. Demeclocycline (DEM): Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligrams (mg) DEM will be taken orally every 6 hours; Days 4 to15: DEM will not be administered. Tetracycline (TET): Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 milligrams per day (mg/day) administered orally. Vitamin D: Approximately 800 to 1200 International Units per day (IU/day) administered orally. |
Drug: Teriparatide
Administered SC
Other Names:
Drug: Demeclocycline
Administered orally
Drug: Tetracycline
Administered orally
Drug: Calcium Supplement
Administered orally
Drug: Vitamin D
Administered orally
|
| Active Comparator: Denosumab 60 mg denosumab administered SC once in 6 months. DEM: Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 mg DEM will be taken orally every 6 hours; Days 4 to 15: DEM will not be administered. TET: Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 mg/day administered orally. Vitamin D: Approximately 800 to 1200 IU/day administered orally. |
Drug: Denosumab
Administered SC
Drug: Demeclocycline
Administered orally
Drug: Tetracycline
Administered orally
Drug: Calcium Supplement
Administered orally
Drug: Vitamin D
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies [Baseline, 3 months post first dose of study drug]
MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling, and calculated as the sum of the total extent of double label (DL) plus half the extent of single label (SL) divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or no label (NL) suggested varying degrees of suppression of bone formation.
Secondary Outcome Measures
- Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies [3 months post first dose of study drug]
- Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies [Baseline, 3 months post first dose of study drug]
MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation.
- MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug [3 months post first dose of study drug]
MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation.
- Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies [3 months post first dose of study drug]
In this study, post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling-based bone formations which was determined by whether the underlying reversal line was scalloped or smooth and by the collagen fiber orientation. Percentage = (remodeling-based formation units or modeling-based formation units/ total bone formation units) * 100.
- Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies [3 months post first dose of study drug]
The percentage of mineralizing surface where post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling based bone formation based on collagen fiber orientation and whether the underlying reversal line was scalloped or smooth. Percentage = percentage remodeling- or modeling-based formation units * MS/BS
- Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies [3 months post first dose of study drug]
The percentage of overfilled remodeling sites in the CC, EC, and PC were defined as the percentage of observed remodeling units in which the second DL (TET) extended beyond the limits of the scalloped reversal line and into the adjacent, previously unresorbed surface of the bone. Percentage = (overfilled remodeling bone formation unit / total bone formation unit) * 100.
- Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies [Baseline, 3 months post first dose of study drug]
BMUs are local groups of osteoblasts and osteoclasts that act in concert to complete a single remodeling cycle. The label length is a measure of the extent of the mineralization front within each BMU in the CC, EC, IC and PC. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation.
- Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies [Baseline, 3 months post first dose of study drug]
MAR is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between 2 consecutive labels divided by the time interval. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation. SL cases were imputed to a value of 0.3 micrometers per day (µm/day) or counted as missing. NL cases were reported as missing.
- Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies [Baseline, 3 months post first dose of study drug]
BFR/BS is the volume of mineralized bone formed per unit surface of bone per unit of time [mm cubed per mm squared per year (mm³/mm²/year)]. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicates active bone formation, a SL or NL suggests suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 mcm/day or counted as missing. NL cases were assigned a value of zero.
- Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies [3 months post first dose of study drug]
At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. Percentage = (Single or double TET labels / BS) *100.
- Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) [Baseline, 1, 3, and 6 months post first dose of study drug]
PTH regulates calcium and phosphate metabolism in bone and kidney, and is typically measured in serum using the intact PTH assay. Percentage = (PTH value at specified time points - PTH value at baseline) / PTH value at baseline * 100.
- Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) [Baseline, 1, 3, and 6 months post first dose of study drug]
P1NP is a marker of bone turnover and is a measure of bone formation. Percentage = (P1NP value at specified time points - P1NP value at baseline) / P1NP value at baseline * 100.
- Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin [Baseline, 1, 3, and 6 months post first dose of study drug]
Osteocalcin is a marker of bone turnover and a measure of osteoblast function. Percentage = (osteocalcin value at specified time points - osteocalcin value at baseline) / (osteocalcin value at baseline) * 100.
- Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) [Baseline, 1, 3, and 6 months post first dose of study drug]
CTX is a marker of bone turnover and is a measure of bone resorption. Percentage = (CTX value at specified time points - CTX value at baseline) / (CTX value at baseline) * 100.
- Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
Ac.f is the probability of new remodeling cycles initiated on the BS per year. Ac.f = (BFR/BS) / wall thickness. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were assigned a value of zero.
- Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
Aj.AR is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were counted as missing.
- Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest [3 months post first dose of study drug]
OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) *100.
- Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) *100.
- Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
O.Th is a measure of the average thickness of osteoid seams.
- Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets.
- Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest [3 months post first dose of study drug]
ES/BS 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. Percentage = (ES/BS) *100.
Other Outcome Measures
- Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest [3 months post first dose of study drug]
The length of TET DLs is a measure of the extent of bone formation in each compartment within individual remodeling units and is measured in mm. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation.
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 (no vaginal bleeding for at least 2 years prior to screening) with osteoporosis
-
Bone mineral density (BMD) T-score of at least -2.5 at femoral neck (FN), total hip (TH), or lumbar spine (LS) (Lumbar vertebrae L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture after menopause, OR
-
BMD T-score of at least -1.5 at FN, TH, or LS (L1-L4, with at least 2 evaluable vertebrae), and 1 or more atraumatic fractures after menopause (vertebral or nonvertebral). Nonvertebral fracture sites allowed are wrist, hip, pelvis, rib, humerus, clavicle, leg (femur, tibia, and fibula, excluding ankle)
-
Laboratory values for serum calcium, parathyroid hormone (PTH), and alkaline phosphatase must be within the normal reference range
Exclusion Criteria:
-
Has an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton
-
Has an allergy or intolerance to teriparatide or denosumab and/or is a poor candidate for teriparatide or denosumab treatment (investigator should refer to local product prescribing information)
-
Has a history of exposure to DEM or TET therapy in the 12 months prior to screening or a known allergy to DEM or TET
-
Has a condition that could put the participant at additional risk of an adverse event (AE) due to the bone biopsy procedure (for example, bleeding disorder)
-
Has undergone 2 previous iliac crest bone biopsies (1 in each iliac crest)
-
Has a 25-hydroxyvitamin D concentration of <10 nanograms per milliliter (ng/mL)
-
Has currently active or suspected (within 1 year prior to enrollment) diseases that affect bone metabolism, other than osteoporosis (such as renal osteodystrophy, hyperthyroidism, osteomalacia, or hyperparathyroidism)
-
Has a history of certain cancers within 5 years prior to trial entry
-
Current or recent (within 1 year prior to enrollment) celiac disease, inflammatory bowel disease, gastric bypass, or other malabsorption syndrome
-
Has significantly impaired hepatic or renal function
-
Has had treatment with systemic glucocorticoids in doses ≥5 mg/day prednisone/day or equivalent in the 6 calendar months prior to screening
-
Has taken any intravenous osteoporosis medication
-
Has had prior treatment with other bisphosphonates and not been off of them for a specific period of time before trial entry
-
Has participated in any other clinical trial studying teriparatide, PTH, PTH analog, or denosumab, or prior or current treatment with teriparatide, PTH, PTH analog, or denosumab
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. | Gainesville | Georgia | United States | 30501 |
| 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. | Detroit | Michigan | United States | 48202 |
| 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. | Omaha | Nebraska | United States | 68131 |
| 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. | Vancouver | British Columbia | Canada | V5Z 4E1 |
| 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. | 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 9AM - 5PM 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:
NCT01753856
Other Study ID Numbers:
- 14592
- B3D-US-GHDV
First Posted:
Dec 20, 2012
Last Update Posted:
Oct 8, 2015
Last Verified:
Sep 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Tetracycline (TET) and demeclocycline (DEM) temporarily bind to new bone and are detected as different colors under ultraviolet light in bone biopsy samples. In this study, participants were administered DEM prior to randomization (baseline) and again with TET 22 days prior to bone biopsy obtained 3 months post first dose of study drug. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-microgram (µg) subcutaneous (SC) injection once daily for 6 months. DEM: 150-milligram (mg) tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 milligrams per day (mg/day) administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 International Units per day (IU/day) administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Period Title: Overall Study | ||
| STARTED | 33 | 36 |
| Received at Least 1 Dose of Study Drug | 33 | 36 |
| Completed 3-Month Bone Biopsy | 31 | 35 |
| COMPLETED | 30 | 34 |
| NOT COMPLETED | 3 | 2 |
Baseline Characteristics
| Arm/Group Title | Teriparatide | Denosumab | Total |
|---|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Total of all reporting groups |
| Overall Participants | 33 | 36 | 69 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
61.58
(5.84)
|
65.17
(8.32)
|
63.45
(7.42)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
33
100%
|
36
100%
|
69
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
2
6.1%
|
3
8.3%
|
5
7.2%
|
| Not Hispanic or Latino |
31
93.9%
|
32
88.9%
|
63
91.3%
|
| Unknown or Not Reported |
0
0%
|
1
2.8%
|
1
1.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
2
5.6%
|
2
2.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
3%
|
2
5.6%
|
3
4.3%
|
| White |
31
93.9%
|
31
86.1%
|
62
89.9%
|
| More than one race |
1
3%
|
1
2.8%
|
2
2.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
21
63.6%
|
27
75%
|
48
69.6%
|
| Canada |
12
36.4%
|
9
25%
|
21
30.4%
|
Outcome Measures
| Title | Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies |
|---|---|
| Description | MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling, and calculated as the sum of the total extent of double label (DL) plus half the extent of single label (SL) divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or no label (NL) suggested varying degrees of suppression of bone formation. |
| Time Frame | Baseline, 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the CC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| Median (Inter-Quartile Range) [percentage of BS] |
12.43
|
-2.51
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) model with treatment group as the main effect and baseline MS/BS as a covariate. | |
| Title | Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies |
|---|---|
| Description | |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of the number of samples with specified labels in the various compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| DL and SL, in CC (n=31, 35) |
31
|
24
|
| DL Only, in CC (n=31, 35) |
0
|
0
|
| SL Only, in CC (n=31, 35) |
0
|
9
|
| No Label, in CC (n=31, 35) |
0
|
2
|
| DL and SL, in EC (n=30, 35) |
30
|
25
|
| DL Only, in EC (n=30, 35) |
0
|
0
|
| SL Only, in EC (n=30, 35) |
0
|
6
|
| No Label, in EC (n=30, 35) |
0
|
4
|
| DL and SL, in IC (n=30, 35) |
30
|
24
|
| DL Only, in IC (n=30, 35) |
0
|
0
|
| SL Only, in IC (n=30, 35) |
0
|
10
|
| No Label, in IC (n=30, 35) |
0
|
1
|
| DL and SL, in PC (n=30, 35) |
10
|
1
|
| DL Only, in PC (n=30, 35) |
0
|
0
|
| SL Only, in PC (n=30, 35) |
19
|
4
|
| No Label, in PC (n=30, 35) |
1
|
30
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and SL, in CC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | SL Only, in CC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.494 |
| Comments | No Label, in CC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | DL and SL, in EC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | SL Only, in EC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.118 |
| Comments | No Label, in EC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and SL, in IC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | SL Only, in IC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.999 |
| Comments | No Label, in IC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | DL and SL, in PC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | SL Only, in PC. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | No Label, in PC. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies |
|---|---|
| Description | MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation. |
| Time Frame | Baseline, 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 30 | 35 |
| EC |
26.12
|
-2.97
|
| IC |
9.39
|
-6.70
|
| PC |
2.40
|
-0.39
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
| Title | MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug |
|---|---|
| Description | MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| CC (n=31, 35) |
18.73
|
0.96
|
| EC (n=30, 35) |
39.50
|
5.42
|
| IC (n=30, 35) |
21.69
|
3.05
|
| PC (n=30, 35) |
4.69
|
0.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | PC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | In this study, post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling-based bone formations which was determined by whether the underlying reversal line was scalloped or smooth and by the collagen fiber orientation. Percentage = (remodeling-based formation units or modeling-based formation units/ total bone formation units) * 100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling-based or modeling-based formation in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 32 |
| Remodeling-Based Bone Formation in CC (n=31, 32) |
89.02
|
90.83
|
| Modeling-Based Bone Formation in CC (n=31, 32) |
10.98
|
9.17
|
| Remodeling-Based Bone Formation in EC (n=30, 29) |
83.33
|
100.00
|
| Modeling-Based Bone Formation in EC (n=30, 29) |
16.67
|
0.00
|
| Remodeling-Based Bone Formation in PC (n=29, 5) |
0.00
|
0.00
|
| Modeling-Based Bone Formation in PC (n=29, 5) |
100.0
|
100.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.740 |
| Comments | Remodeling-Based Bone Formation in the CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.740 |
| Comments | Modeling-Based Bone Formation in the CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | Remodeling-Based Bone Formation in the EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | Modeling-Based Bone Formation in the EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.661 |
| Comments | Remodeling-Based Bone Formation in the PC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.661 |
| Comments | Modeling-Based Bone Formation in the PC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | The percentage of mineralizing surface where post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling based bone formation based on collagen fiber orientation and whether the underlying reversal line was scalloped or smooth. Percentage = percentage remodeling- or modeling-based formation units * MS/BS |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling- or modeling-based formation in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| Remodeling-Based Bone Formation in CC (n=31, 35) |
16.67
|
0.87
|
| Modeling-Based Bone Formation in CC (n=31, 35) |
2.06
|
0.09
|
| Remodeling-Based Bone Formation in EC (n=30, 35) |
32.92
|
5.42
|
| Modeling-Based Bone Formation in EC (n=30, 35) |
6.58
|
0.00
|
| Remodeling-Based Bone Formation in PC (n=30, 35) |
0.00
|
0.00
|
| Modeling-Based Bone Formation in PC (n=30, 35) |
4.69
|
0.00
|
| Title | Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | The percentage of overfilled remodeling sites in the CC, EC, and PC were defined as the percentage of observed remodeling units in which the second DL (TET) extended beyond the limits of the scalloped reversal line and into the adjacent, previously unresorbed surface of the bone. Percentage = (overfilled remodeling bone formation unit / total bone formation unit) * 100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy evaluated for overfilled remodeling sites in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 32 |
| CC (n=31, 32) |
17.74
|
0.00
|
| EC (n=30, 29) |
21.98
|
0.00
|
| PC (n=29, 5) |
0.00
|
0.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.740 |
| Comments | PC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | BMUs are local groups of osteoblasts and osteoclasts that act in concert to complete a single remodeling cycle. The label length is a measure of the extent of the mineralization front within each BMU in the CC, EC, IC and PC. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation. |
| Time Frame | Baseline, 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label lengths measured in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 30 | 25 |
| CC (n=30, 24) |
0.19
|
0.05
|
| EC (n=28, 25) |
0.25
|
0.03
|
| IC (n=30, 24) |
0.18
|
0.02
|
| PC (n=4, 1) |
0.12
|
0.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.850 |
| Comments | PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
| Title | Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | MAR is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between 2 consecutive labels divided by the time interval. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation. SL cases were imputed to a value of 0.3 micrometers per day (µm/day) or counted as missing. NL cases were reported as missing. |
| Time Frame | Baseline, 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an evaluation of MAR in the CC, EC, IC and PC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 34 |
| DL Only, in CC (n=30, 24) |
0.00
|
-0.04
|
| DL and Imputed SL, in CC (n=31, 33) |
0.01
|
-0.06
|
| DL Only, in EC (n=28, 25) |
0.03
|
-0.07
|
| DL and Imputed SL, in EC (n=29, 31) |
0.03
|
-0.09
|
| DL Only, in IC (n=30, 24) |
0.20
|
-0.18
|
| DL and Imputed SL, in IC (n=30, 34) |
0.20
|
-0.22
|
| DL Only, in PC (n=4, 1) |
0.05
|
-0.04
|
| DL and Imputed SL, in PC (n=19, 4) |
0.00
|
-0.04
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | DL Only, in CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in the CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.931 |
| Comments | DL Only, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.549 |
| Comments | DL and Imputed SL, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
| Title | Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | BFR/BS is the volume of mineralized bone formed per unit surface of bone per unit of time [mm cubed per mm squared per year (mm³/mm²/year)]. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicates active bone formation, a SL or NL suggests suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 mcm/day or counted as missing. NL cases were assigned a value of zero. |
| Time Frame | Baseline, 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with BFR/BS assessments in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| DL Only, in CC (n=30, 26) |
0.0280
|
-0.0056
|
| DL and Imputed SL, in CC (n=31, 35) |
0.0275
|
-0.0055
|
| DL Only, in EC (n=29, 28) |
0.0509
|
-0.0069
|
| DL and Imputed SL, in EC (n=30, 35) |
0.0501
|
-0.0069
|
| DL Only, in IC (n=30, 25) |
0.0455
|
-0.0184
|
| DL and Imputed SL, in IC (n=30, 35) |
0.0455
|
-0.0184
|
| DL Only, in PC (n=6, 16) |
0.0231
|
0.0000
|
| DL and Imputed SL, in PC (n=30, 35) |
0.0015
|
-0.0005
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
| Title | Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
|---|---|
| Description | At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. Percentage = (Single or double TET labels / BS) *100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label surface measured in the specified compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| sLS/BS, in CC (n=31, 35) |
15.44
|
1.28
|
| dLS/BS, in CC (n=31, 35) |
10.44
|
0.22
|
| sLS/BS, in EC (n=30, 35) |
24.24
|
7.18
|
| dLS/BS, in EC (n=30, 35) |
28.84
|
1.68
|
| sLS/BS, in IC (n=30, 35) |
15.28
|
4.66
|
| dLS/BS, in IC (n=30, 35) |
14.96
|
0.83
|
| sLS/BS, in PC (n=30, 35) |
9.37
|
0.00
|
| dLS/BS, in PC (n=30, 35) |
0.00
|
0.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | sLS/BS, in CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | dLS/BS, in CC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | sLS/BS, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | dLS/BS, in EC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | sLS/BS, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | dLS/BS, in IC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | sLS/BS, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | dLS/BS, in PC. | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline as a covariate. | |
| Title | Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) |
|---|---|
| Description | PTH regulates calcium and phosphate metabolism in bone and kidney, and is typically measured in serum using the intact PTH assay. Percentage = (PTH value at specified time points - PTH value at baseline) / PTH value at baseline * 100. |
| Time Frame | Baseline, 1, 3, and 6 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had serum PTH assessed at baseline and the specified time points. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 28 | 34 |
| 1 month (n=28, 34) |
-26.89
|
72.24
|
| 3 months (n=18, 28) |
-32.16
|
46.68
|
| 6 months (n=27, 33) |
-40.18
|
30.40
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 1 month. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 3 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 6 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) |
|---|---|
| Description | P1NP is a marker of bone turnover and is a measure of bone formation. Percentage = (P1NP value at specified time points - P1NP value at baseline) / P1NP value at baseline * 100. |
| Time Frame | Baseline, 1, 3, and 6 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had serum P1NP measurements at baseline and the specified time points. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 33 | 34 |
| 1 month (n=33, 34) |
134.38
|
-11.56
|
| 3 months (n=22, 29) |
213.15
|
-66.64
|
| 6 months (n=31, 32) |
284.22
|
-68.24
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 1 month. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 3 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 6 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin |
|---|---|
| Description | Osteocalcin is a marker of bone turnover and a measure of osteoblast function. Percentage = (osteocalcin value at specified time points - osteocalcin value at baseline) / (osteocalcin value at baseline) * 100. |
| Time Frame | Baseline, 1, 3, and 6 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had serum osteocalcin measured at baseline and the specified time points. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 33 |
| 1 month (n=31, 33) |
90.53
|
-6.56
|
| 3 months (n=20, 29) |
123.66
|
-45.70
|
| 6 months (n=29, 31) |
187.29
|
-50.53
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 1 month. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 3 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 6 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) |
|---|---|
| Description | CTX is a marker of bone turnover and is a measure of bone resorption. Percentage = (CTX value at specified time points - CTX value at baseline) / (CTX value at baseline) * 100. |
| Time Frame | Baseline, 1, 3, and 6 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and serum CTX measured at baseline and the specified time points. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 33 |
| 1 month (n=31, 33) |
6.09
|
-90.70
|
| 3 months (n=21, 29) |
73.04
|
-90.77
|
| 6 months (n=29, 33) |
89.13
|
-82.50
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 1 month. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 3 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 6 months. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | Ac.f is the probability of new remodeling cycles initiated on the BS per year. Ac.f = (BFR/BS) / wall thickness. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were assigned a value of zero. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Ac.f assessments in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| DL Only, in CC (n=31, 26) |
1.41
|
0.10
|
| DL and Imputed SL, in CC (n=31, 35) |
1.41
|
0.06
|
| DL Only, in EC (n=30, 29) |
2.77
|
0.35
|
| DL and Imputed SL, in EC (n=30, 35) |
2.77
|
0.34
|
| DL Only, in IC (n=30, 25) |
1.88
|
0.17
|
| DL and Imputed SL, in IC (n=30, 35) |
1.88
|
0.12
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | Aj.AR is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. BFR = MAR * (MS/BS). SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were counted as missing. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Aj.AR assessments in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 33 |
| DL Only, in CC (n=31, 24) |
0.58
|
0.21
|
| DL and Imputed SL, in CC (n=31, 33) |
0.58
|
0.14
|
| DL Only, in EC (n=30, 25) |
0.76
|
0.65
|
| DL and Imputed SL, in EC (n=30, 30) |
0.76
|
0.58
|
| DL Only, in IC (n=30, 24) |
1.03
|
0.58
|
| DL and Imputed SL, in IC (n=30, 33) |
1.03
|
0.35
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | DL Only, in CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.214 |
| Comments | DL Only, in EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | DL and Imputed SL, in EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL Only, in IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | DL and Imputed SL, in IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest |
|---|---|
| Description | OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) *100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of OV/BV in the CC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| Median (Inter-Quartile Range) [percentage of BV] |
2.58
|
0.39
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) *100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the assessment of OS/BS in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| CC (n=31, 35) |
20.51
|
3.46
|
| EC (n=30, 35) |
30.85
|
6.95
|
| IC (n=30, 35) |
17.81
|
4.34
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | O.Th is a measure of the average thickness of osteoid seams. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an O.Th assessment in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-mcg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| CC (n= 31, 35) |
6.12
|
3.78
|
| EC (n= 30, 35) |
6.99
|
4.33
|
| IC (n= 30, 35) |
7.08
|
4.68
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest |
|---|---|
| Description | The length of TET DLs is a measure of the extent of bone formation in each compartment within individual remodeling units and is measured in mm. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of DL length in the various compartments of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 25 |
| DL, in CC (n=31, 24) |
0.40
(0.08)
|
0.31
(0.10)
|
| DL, in EC (n=30, 25) |
0.48
(0.15)
|
0.35
(0.20)
|
| DL, in IC (n=30, 24) |
0.43
(0.11)
|
0.27
(0.12)
|
| DL, in PC (n=10, 1) |
0.38
(0.41)
|
0.32
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Average length of DLs in the CC | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | Average length of double labels in EC | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Average length of double labels in IC | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.850 |
| Comments | Average length of double labels in the PC | |
| Method | ANCOVA | |
| Comments | ANCOVA model with treatment group as the main effect and baseline MS/BS as a covariate. | |
| Title | Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with a W. Th assessment in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| CC (n=31, 35) |
26.29
|
24.03
|
| EC (n=30, 35) |
31.88
|
30.08
|
| IC (n=30, 35) |
38.25
|
37.80
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.042 |
| Comments | EC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.678 |
| Comments | IC. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest |
|---|---|
| Description | ES/BS 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. Percentage = (ES/BS) *100. |
| Time Frame | 3 months post first dose of study drug |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with ES/BS assessed in the CC, EC and IC of the iliac crest. |
| Arm/Group Title | Teriparatide | Denosumab |
|---|---|---|
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. |
| Measure Participants | 31 | 35 |
| CC (n=31, 35) |
3.73
|
1.52
|
| EC (n=30, 35) |
3.79
|
1.65
|
| IC (n=30, 35) |
11.19
|
1.27
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | CC | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | EC | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Teriparatide, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | IC | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Teriparatide | Denosumab | ||
| Arm/Group Description | Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months. | ||
All Cause Mortality |
||||
| Teriparatide | Denosumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Teriparatide | Denosumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/33 (6.1%) | 2/36 (5.6%) | ||
| General disorders | ||||
| Chest pain | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Infections and infestations | ||||
| Appendicitis | 0/33 (0%) | 0 | 1/36 (2.8%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Lung adenocarcinoma | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/33 (0%) | 0 | 1/36 (2.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Teriparatide | Denosumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/33 (81.8%) | 23/36 (63.9%) | ||
| Blood and lymphatic system disorders | ||||
| Lymph node pain | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Eye disorders | ||||
| Dry eye | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Abdominal pain | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Abdominal pain lower | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Constipation | 1/33 (3%) | 1 | 4/36 (11.1%) | 4 |
| Diarrhoea | 1/33 (3%) | 1 | 1/36 (2.8%) | 1 |
| Gastrooesophageal reflux disease | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Nausea | 4/33 (12.1%) | 4 | 0/36 (0%) | 0 |
| General disorders | ||||
| Fatigue | 4/33 (12.1%) | 5 | 1/36 (2.8%) | 1 |
| Injection site erythema | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Local swelling | 2/33 (6.1%) | 2 | 0/36 (0%) | 0 |
| Thirst | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 3/33 (9.1%) | 3 | 1/36 (2.8%) | 1 |
| Ear infection | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Gastroenteritis | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Nasopharyngitis | 1/33 (3%) | 1 | 2/36 (5.6%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 10/33 (30.3%) | 10 | 4/36 (11.1%) | 4 |
| Fall | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Post procedural discomfort | 1/33 (3%) | 1 | 4/36 (11.1%) | 4 |
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 2/33 (6.1%) | 2 | 1/36 (2.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 5/33 (15.2%) | 6 | 1/36 (2.8%) | 1 |
| Bone pain | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Foot deformity | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Groin pain | 1/33 (3%) | 1 | 1/36 (2.8%) | 1 |
| Joint stiffness | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Joint swelling | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Muscular weakness | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Pain in extremity | 3/33 (9.1%) | 5 | 1/36 (2.8%) | 1 |
| Sensation of heaviness | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Tendon disorder | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Nervous system disorders | ||||
| Dizziness | 1/33 (3%) | 2 | 0/36 (0%) | 0 |
| Dysgeusia | 2/33 (6.1%) | 2 | 0/36 (0%) | 0 |
| Headache | 4/33 (12.1%) | 6 | 0/36 (0%) | 0 |
| Loss of consciousness | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Tremor | 1/33 (3%) | 1 | 1/36 (2.8%) | 1 |
| Renal and urinary disorders | ||||
| Bladder spasm | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Nephrolithiasis | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Urine abnormality | 2/33 (6.1%) | 2 | 0/36 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Vaginal discharge | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Cough | 3/33 (9.1%) | 3 | 1/36 (2.8%) | 1 |
| Oropharyngeal pain | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Sneezing | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Hyperhidrosis | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Onychoclasis | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Pruritus | 1/33 (3%) | 2 | 1/36 (2.8%) | 1 |
| Rash | 2/33 (6.1%) | 2 | 2/36 (5.6%) | 2 |
| Skin induration | 1/33 (3%) | 1 | 1/36 (2.8%) | 1 |
| Swelling face | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Urticaria | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Vascular disorders | ||||
| Haematoma | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Hypotension | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
| Spider vein | 1/33 (3%) | 1 | 0/36 (0%) | 0 |
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 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01753856
Other Study ID Numbers:
- 14592
- B3D-US-GHDV
First Posted:
Dec 20, 2012
Last Update Posted:
Oct 8, 2015
Last Verified:
Sep 1, 2015