Evaluation of the Effects of Teriparatide on Skeleton Images in Postmenopausal Women With Osteoporosis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00259298
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 44
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of teriparatide on skeleton images in postmenopausal women with osteoporosis. Teriparatide is a bone formation agent that stimulates the production of new bone in the skeleton. This process of bone formation can be studied using a technique commonly referred to as a bone scan or nuclear scintigraphy. This trial will test whether bone scans will identify areas of the skeleton that are forming new bone during teriparatide therapy. It also will study what these areas look like after therapy is stopped.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: teriparatide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Use of Nuclear Scintigraphy to Evaluate the Anabolic Effects of Teriparatide on the Skeleton in Postmenopausal Women With Osteoporosis
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Teriparatide Participants receive teriparatide 20 microgram once daily by subcutaneous injection for 18 months followed by 6 months off therapy	Drug: teriparatide; Subcutaneous, 20 microgram (mcg)/day, 18 months; Other Names: LY333334 Forteo Forsteo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Whole Skeleton Skeletal Plasma Clearance of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) to 18 Months [baseline, 18 months]

   Skeletal plasma clearance is defined as the volume of plasma cleared of tracer (99m Tc-MDP) by the skeleton per unit time (milliliter/minute). Kbone is the rate constant representing plasma clearance of tracer to bone. The Patlak plot method was used to evaluate whole skeleton 99mTc-MDP skeletal plasma clearance (Kbone).

Secondary Outcome Measures

1. Change in Skeletal Plasma Clearance of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton, Skull, Mandible, Spine, Pelvis, Upper Extremities, and Lower Extremities [Baseline, 3 months, 18 months, 24 months]

   Skeletal plasma clearance is defined as the volume of plasma cleared of tracer (99m Tc-MDP) by the skeleton per unit time (milliliter/minute). Kbone is the rate constant representing plasma clearance of tracer to bone. The Patlak plot method was used to evaluate whole skeleton 99mTc-MDP skeletal plasma clearance (Kbone) and to derive regional values for the skull, mandible, spine, pelvis, and upper and lower extremities.

2. Change in Skeletal Uptake of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton, Skull, Mandible, Spine, Pelvis, Upper Extremities, and Lower Extremities [Baseline, 3 months, 18 months, 24 months]

   Skeletal uptake describes the percent uptake of radionuclide tracer by the skeleton when compared to baseline or other post-baseline measures. Skeletal uptake is defined as percentage of uptake of 99mTc-MDP 4 hours after injection. This value differs from skeletal plasma clearance measurements because it only quantifies the amount of 99mTc-MDP taken up by bone without consideration of concentration of tracer in the plasma.

3. Change in Qualitative Visual Scores of Focal Uptake of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton [Baseline, 3 months, 18 months, 24 months]

   Changes in focal uptake (localized, defined areas of uptake) were visually scored and compared to baseline or other post-baseline assessments. Changes were rated on a scale from 0-4: 0=no clinically significant focal areas of skeletal uptake; 1=focal areas affecting <1% of skeleton; 2=focal areas affecting >=5% of skeleton; 3=focal areas affecting >=20% of skeleton; 4=focal areas affecting >=50% of skeleton.

4. Number of Participants With Changes in Diffuse Uptake of 99m Tc-MDP - Qualitative Visual Assessment in the Whole Skeleton [baseline, 3 months, 18 months, 24 months]

   Changes in diffuse uptake were determined by comparing diffuse uptake to baseline or other post-baseline observations. Diffuse uptake indicates response to therapy (during active treatment, increased diffuse uptake was expected; after the 6-month withdrawal period, decreased diffuse uptake was expected). Qualitative visual scoring of changes in the bone scan images were performed jointly by 3 reviewers who classified changes in the whole skeleton into 4 groups as follows: possible decreased response, no response, possible response, and definite response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory with osteoporosis

• Hip or spine bone mineral density (BMD) measurement more than 2.5 standard deviations below the average bone mass of young healthy women or more than 2.0 standard deviations in women who have a history of a vertebral or nonvertebral fragility fracture.

Exclusion Criteria:

• Diseases of bone other than osteoporosis

• Treatment with estrogens in the 3 months prior to enrollment or for more than 2 months in the past year

• Treatment with oral bisphosphonates in the 3 months prior to enrollment or for more than 2 months in the past year; treatment with intravenous bisphosphonates in the 12 months prior to enrollment

• Increased risk for the development of osteosarcoma

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	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00259298
• Other Study ID Numbers: 9917; B3D-US-GHCV
• First Posted: Nov 29, 2005
• Last Update Posted: Aug 11, 2010
• Last Verified: Jul 1, 2010

• Additional relevant MeSH terms: Osteoporosis; Teriparatide

Study Results

Participant Flow

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Period Title: Overall Study
STARTED	12
Received at Least 1 Dose of Study Drug	10
COMPLETED	9
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.17 (7.64)
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	12 100%
Region of Enrollment (participants) [Number]
United Kingdom	12 100%
Qualitative Visual Assessment of Diffuse Uptake of 99m Technetium methylene diphosphonate (participants) [Number]
no increase	10 83.3%
possible increase	0 0%
definite increase	0 0%
not assessed	2 16.7%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	24.56 (5.16)
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	161.25 (6.88)
Qualitative Visual Score of Focal uptake of 99m Technetium methylene diphosphonate (99m Tc-MDP) (units on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on scale]	0.7 (0.48)
Skeletal plasma clearance of 99m Technetium methylene diphosphonate (99m Tc-MDP) (milliliter/minute) [Median (Inter-Quartile Range) ]
whole skeleton	38.30
skull	3.07
mandible	0.17
spine	6.32
pelvis	5.92
upper extremities	3.70
lower extremities	9.12
Skeletal uptake of 99m Technetium methylene diphosphonate (99m Tc-MDP) (percentage of uptake) [Median (Inter-Quartile Range) ]
whole skeleton	29.4
skull	2.59
mandible	0.14
spine	4.85
pelvis	4.57
upper extremities	2.98
lower extremities	7.09
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	63.80 (13.56)
Years post menopause (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.84 (7.65)

Outcome Measures

1. Secondary Outcome

Title	Change in Skeletal Plasma Clearance of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton, Skull, Mandible, Spine, Pelvis, Upper Extremities, and Lower Extremities
Description	Skeletal plasma clearance is defined as the volume of plasma cleared of tracer (99m Tc-MDP) by the skeleton per unit time (milliliter/minute). Kbone is the rate constant representing plasma clearance of tracer to bone. The Patlak plot method was used to evaluate whole skeleton 99mTc-MDP skeletal plasma clearance (Kbone) and to derive regional values for the skull, mandible, spine, pelvis, and upper and lower extremities.
Time Frame	Baseline, 3 months, 18 months, 24 months

Outcome Measure Data

Analysis Population Description

All participants with a baseline observation and at least 1 post-baseline observation.

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Measure Participants	10
Whole skeleton, baseline to 3 months, n=10	25.02
Whole skeleton, baseline to 24 months, n=9	3.52
Whole skeleton, 3 months to 18 months, n=10	10.44
Whole skeleton, 18 months to 24 months, n=9	-22.20
Skull, baseline to 3 months, n=8	72.25
Skull, baseline to 18 months, n=8	128.44
Skull, baseline to 24 months, n=7	21.20
Skull, 3 months to 18 months, n=8	31.01
Skull, 18 months to 24 months, n=7	-37.87
Mandible, baseline to 3 months, n=8	65.94
Mandible, baseline to 18 months, n=8	60.99
Mandible, baseline to 24 months, n=7	21.05
Mandible, 3 months to 18 months, n=8	4.55
Mandible, 18 months to 24 months, n=7	-17.39
Spine, baseline to 3 months, n=10	17.31
Spine, baseline to 18 months, n=10	33.81
Spine, baseline to 24 months, n=9	16.94
Spine, 3 months to 18 months, n=10	14.10
Spine, 18 months to 24 months, n=9	-9.42
Pelvis, baseline to 3 months, n=10	20.26
Pelvis, baseline to 18 months, n=10	8.36
Pelvis, baseline to 24 months, n=9	-5.58
Pelvis, 3 months to 18 months, n=10	-3.29
Pelvis, 18 months to 24 months, n=9	-13.81
Upper extremities, baseline to 3 months, n=10	42.52
Upper extremities, baseline to 18 months, n=10	95.49
Upper extremities, baseline to 24 months, n=9	62.76
Upper extremities, 3 months to 18 months, n=10	45.84
Upper extremities, 18 months to 24 months, n=9	-19.35
Lower extremities, baseline to 3 months, n=10	20.98
Lower extremities, baseline to 18 months, n=10	34.88
Lower extremities, baseline to 24 months, n=9	7.07
Lower extremities, 3 months to 18 months, n=10	12.72
Lower extremities, 18 months to 24 months, n=9	-20.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the skull from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the skull from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the skull from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments	p-value is for skull, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the skull from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the skull from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments	p-value is for skull, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the mandible from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments	p-value is for mandible, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the mandible from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for mandible, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the mandible from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1563
	Comments	p-value is for mandible, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the mandible from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4375
	Comments	p-value is for mandible, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the mandible from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments	p-value is for mandible, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the spine from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0371
	Comments	p-value is for spine, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the spine from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments	p-value is for spine, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the spine from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0547
	Comments	p-value is for spine, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the spine from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0488
	Comments	p-value is for spine, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the spine from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3594
	Comments	p-value is for spine, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the pelvis from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0488
	Comments	p-value is for pelvis, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the pelvis from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1055
	Comments	p-value is for pelvis, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the pelvis from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9102
	Comments	p-value is for pelvis, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the pelvis from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments	p-value is for pelvis, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the pelvis from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1641
	Comments	p-value is for pelvis, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the upper extremities from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments	p-value is for upper extremities, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the upper extremities from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments	p-value is for upper extremities, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the upper extremities from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value is for upper extremities, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the upper extremities from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	p-value is for upper extremities, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the upper extremities from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0547
	Comments	p-value is for upper extremities, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the lower extremities from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0195
	Comments	p-value is for lower extremities, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the lower extremities from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments	p-value is for lower extremities, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the lower extremities from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5703
	Comments	p-value is for lower extremities, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the lower extremities from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments	p-value is for lower extremities, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the lower extremities from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value is for lower extremities, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the whole body from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value is for whole body, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal plasma clearance of 99m Tc-MDP in the whole body from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5703
	Comments	p-value is for whole body, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal plasma clearance of 99m Tc-MDP in the whole body from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	p-value is for whole body, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal plasma clearance of 99m Tc-MDP in the whole body from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value if for whole body, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

2. Secondary Outcome

Title	Change in Skeletal Uptake of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton, Skull, Mandible, Spine, Pelvis, Upper Extremities, and Lower Extremities
Description	Skeletal uptake describes the percent uptake of radionuclide tracer by the skeleton when compared to baseline or other post-baseline measures. Skeletal uptake is defined as percentage of uptake of 99mTc-MDP 4 hours after injection. This value differs from skeletal plasma clearance measurements because it only quantifies the amount of 99mTc-MDP taken up by bone without consideration of concentration of tracer in the plasma.
Time Frame	Baseline, 3 months, 18 months, 24 months

Outcome Measure Data

Analysis Population Description

All participants with a baseline observation and at least 1 post-baseline observation.

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Measure Participants	10
whole skeleton, baseline to 3 months, n=10	15.63
whole skeleton, baseline to 18 months, n=10	26.12
whole skeleton, baseline to 24 months, n=9	5.68
whole skeleton, 3 months to 18 months, n=10	3.99
whole skeleton, 18 months to 24 months, n=9	-14.54
skull, baseline to 3 months, n=8	68.27
skull, baseline to 18 months, n=8	120.85
skull, baseline to 24 months, n=7	26.87
skull, 3 months to 18 months, n=8	23.63
skull, 18 months to 24 months, n=7	-34.36
mandible, baseline to 3 months, n=8	52.20
mandible, baseline to 18 months, n=8	62.91
mandible, baseline to 24 months, n=7	23.08
mandible, 3 months to 18 months, n=8	3.85
mandible, 18 to 24 months, n=7	-6.25
spine, baseline to 3 months, n=10	12.15
spine, baseline to 18 months, n=10	17.77
spine, baseline to 24 months, n=9	17.68
spine, 3 months to 18 months, n=10	13.36
spine, 18 months to 24 months, n=9	-0.19
pelvis, baseline to 3 months, n=10	14.26
pelvis, baseline to 18 months, n=10	-1.21
pelvis, baseline to 24 months, n=9	-1.48
pelvis, 3 months to 18 months, n=10	-3.70
pelvis, 18 months to 24 months, n=9	-5.23
upper extremities, baseline to 3 months, n=10	31.59
upper extremities, baseline to 18 months, n=10	76.58
upper extremities, baseline to 24 months, n=9	57.82
upper extremities, 3 months to 18 months, n=10	48.58
upper extremities, 18 months to 24 months, n=9	-10.13
lower extremities, baseline to 3 months, n=10	9.25
lower extremities, baseline to 18 months, n=10	23.98
lower extremities, baseline to 24 months, n=9	0.86
lower extremities, 3 months to 18 months, n=10	7.58
lower extremities, 18 months to 24 months, n=9	-16.99

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the whole skeleton from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments	p-value is for whole skeleton, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the whole skeleton from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value is for whole skeleton, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the whole skeleton from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6523
	Comments	p-value is for whole skeleton, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the whole skeleton from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1641
	Comments	p-value is for whole skeleton, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the whole skeleton from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for whole skeleton, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the skull from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the skull from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal uptake of 99m Tc-MDP in the skull from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments	p-value is for skull, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the skull from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments	p-value is for skull, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the skull from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0156
	Comments	p-value is for skull, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the mandible from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0391
	Comments	p-value is for mandible, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the mandible from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments	p-value is for mandible, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the mandible from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2969
	Comments	p-value is for mandible, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the mandible from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5625
	Comments	p-value is for mandible, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the mandible from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0469
	Comments	p-value is for mandible, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the spine from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments	p-value is for spine, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the spine from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2324
	Comments	p-value is for spine, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the spine from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0645
	Comments	p-value is for spine, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no change in skeletal uptake of 99m Tc-MDP in the spine from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	p-value is for spine, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the spine from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7344
	Comments	p-value is for spine, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the pelvis from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments	p-value is for pelvis, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the pelvis from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7695
	Comments	p-value is for pelvis, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the pelvis from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6523
	Comments	p-value is for pelvis, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the pelvis from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2324
	Comments	p-value is for pelvis, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the pelvis from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6523
	Comments	p-value is for pelvis, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the upper extremities from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments	p-value is for upper extremities, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the upper extremities from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments	p-value is for upper extremities, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the upper extremities from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value is for upper extremities, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the upper extremities from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	p-value is for upper extremities, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the upper extremities from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3594
	Comments	p-value is for upper extremities, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the lower extremities from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0371
	Comments	p-value is for lower extremities, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the lower extremities from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments	p-value is for lower extremities, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the lower extremities from baseline to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4609
	Comments	p-value is for lower extremities, baseline to 24 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in skeletal uptake of 99m Tc-MDP in the lower extremities from 3 months to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments	p-value is for lower extremities, 3 months to 18 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no decrease in skeletal uptake of 99m Tc-MDP in the lower extremities from 18 months to 24 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments	p-value is for lower extremities, 18 months to 24 months
	Method	Wilcoxon signed rank test
	Comments

3. Secondary Outcome

Title	Change in Qualitative Visual Scores of Focal Uptake of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) in the Whole Skeleton
Description	Changes in focal uptake (localized, defined areas of uptake) were visually scored and compared to baseline or other post-baseline assessments. Changes were rated on a scale from 0-4: 0=no clinically significant focal areas of skeletal uptake; 1=focal areas affecting <1% of skeleton; 2=focal areas affecting >=5% of skeleton; 3=focal areas affecting >=20% of skeleton; 4=focal areas affecting >=50% of skeleton.
Time Frame	Baseline, 3 months, 18 months, 24 months

Outcome Measure Data

Analysis Population Description

All participants with a baseline observation and at least 1 post-baseline observation.

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Measure Participants	10
focal change, baseline to 3 months, n=10	0.1 (0.32)
focal change, baseline to 18 months, n=10	0.1 (0.32)
focal change, baseline to 24 months, n=9	0 (0)
focal change, 3 months to 18 months, n=10	0 (0)
focal change, 18 months to 24 months, n=9	0 (0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in focal skeletal uptake of 99m Tc-MDP from baseline to 3 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	p-value is for focal change, baseline to 3 months
	Method	Wilcoxon signed rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in focal skeletal uptake of 99m Tc-MDP from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	p-value is for focal change, baseline to 18 months
	Method	Wilcoxon signed rank test
	Comments

4. Secondary Outcome

Title	Number of Participants With Changes in Diffuse Uptake of 99m Tc-MDP - Qualitative Visual Assessment in the Whole Skeleton
Description	Changes in diffuse uptake were determined by comparing diffuse uptake to baseline or other post-baseline observations. Diffuse uptake indicates response to therapy (during active treatment, increased diffuse uptake was expected; after the 6-month withdrawal period, decreased diffuse uptake was expected). Qualitative visual scoring of changes in the bone scan images were performed jointly by 3 reviewers who classified changes in the whole skeleton into 4 groups as follows: possible decreased response, no response, possible response, and definite response.
Time Frame	baseline, 3 months, 18 months, 24 months

Outcome Measure Data

Analysis Population Description

All participants with a baseline observation and at least 1 post-baseline observation.

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Measure Participants	10
3 months, no response	2 16.7%
3 months, possible response	2 16.7%
3 months, definite response	6 50%
18 months, no response	1 8.3%
18 months, possible response	1 8.3%
18 months, definite response	8 66.7%
24 months, possible response	1 8.3%
24 months, no response	6 50%
24 months, possible response	1 8.3%
24 months, definite response	1 8.3%

5. Primary Outcome

Title	Change From Baseline in Whole Skeleton Skeletal Plasma Clearance of 99m Technetium Methylene Diphosphonate (99m Tc-MDP) to 18 Months
Description	Skeletal plasma clearance is defined as the volume of plasma cleared of tracer (99m Tc-MDP) by the skeleton per unit time (milliliter/minute). Kbone is the rate constant representing plasma clearance of tracer to bone. The Patlak plot method was used to evaluate whole skeleton 99mTc-MDP skeletal plasma clearance (Kbone).
Time Frame	baseline, 18 months

Outcome Measure Data

Analysis Population Description

All participants with a baseline observation and at least 1 post-baseline observation.

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
Measure Participants	10
Median (Inter-Quartile Range) [percentage of change of plasma clearance]	33.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide
	Comments	Tested was the hypothesis that there would be no increase in whole skeletal plasma clearance of 99m Tc-MDP from baseline to 18 months.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments	p-value is for change at 18 months
	Method	Wilcoxon signed rank test
	Comments

Adverse Events

Arm/Group Title	Teriparatide
Arm/Group Description	Participants received teriparatide 20 microgram once daily by subcutaneous injection for 18 months, followed by 6 months off therapy
All Cause Mortality
	Teriparatide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Teriparatide
	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)
General disorders
Chest pain	1/12 (8.3%)	1
Injury, poisoning and procedural complications
Fall	1/12 (8.3%)	1
Femoral neck fracture	1/12 (8.3%)	1
Ulna fracture	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Teriparatide
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Cardiac disorders
Arrhythmia	2/12 (16.7%)	3
Palpitations	1/12 (8.3%)	1
Tachycardia	1/12 (8.3%)	1
Ear and labyrinth disorders
Ear disorder	1/12 (8.3%)	1
Eustachian tube obstruction	1/12 (8.3%)	1
Tinnitus	2/12 (16.7%)	2
Vertigo	1/12 (8.3%)	2
Eye disorders
Blepharitis	1/12 (8.3%)	1
Cataract	1/12 (8.3%)	1
Chorioretinal disorder	1/12 (8.3%)	1
Optic atrophy	1/12 (8.3%)	1
Vision blurred	1/12 (8.3%)	1
Gastrointestinal disorders
Abdominal discomfort	2/12 (16.7%)	2
Abdominal distension	1/12 (8.3%)	1
Constipation	1/12 (8.3%)	1
Diarrhoea	2/12 (16.7%)	2
Dyspepsia	1/12 (8.3%)	1
Gastrooesophageal reflux disease	2/12 (16.7%)	3
Haemorrhoids	1/12 (8.3%)	1
Hiatus hernia	1/12 (8.3%)	1
Inguinal hernia	1/12 (8.3%)	1
Irritable bowel syndrome	1/12 (8.3%)	1
Lip disorder	1/12 (8.3%)	1
Nausea	3/12 (25%)	4
General disorders
Chest pain	2/12 (16.7%)	2
Cyst	1/12 (8.3%)	1
Fatigue	2/12 (16.7%)	2
Feeling hot	1/12 (8.3%)	1
Injection site erythema	1/12 (8.3%)	2
Injection site haematoma	1/12 (8.3%)	3
Injection site irritation	1/12 (8.3%)	2
Non-cardiac chest pain	1/12 (8.3%)	1
Pain	1/12 (8.3%)	1
Infections and infestations
Eye infection	1/12 (8.3%)	1
Herpes zoster	1/12 (8.3%)	1
Influenza	2/12 (16.7%)	3
Kidney infection	1/12 (8.3%)	1
Nasopharyngitis	1/12 (8.3%)	1
Sinusitis	2/12 (16.7%)	2
Upper respiratory tract infection	2/12 (16.7%)	2
Injury, poisoning and procedural complications
Contusion	1/12 (8.3%)	2
Fall	1/12 (8.3%)	1
Femoral neck fracture	1/12 (8.3%)	1
Fibula fracture	1/12 (8.3%)	1
Fracture	1/12 (8.3%)	1
Fractured coccyx	1/12 (8.3%)	1
Thoracic vertebral fracture	1/12 (8.3%)	1
Investigations
Blood pressure increased	2/12 (16.7%)	2
Cardiac murmur	1/12 (8.3%)	1
Weight increased	1/12 (8.3%)	1
Metabolism and nutrition disorders
Anorexia	1/12 (8.3%)	1
Hypercholesterolaemia	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/12 (16.7%)	2
Back pain	3/12 (25%)	3
Bone pain	3/12 (25%)	3
Bursitis	1/12 (8.3%)	2
Exostosis	1/12 (8.3%)	1
Facet joint syndrome	1/12 (8.3%)	1
Intervertebral disc space narrowing	1/12 (8.3%)	1
Myalgia	2/12 (16.7%)	2
Neck pain	2/12 (16.7%)	2
Osteitis deformans	1/12 (8.3%)	1
Osteoarthritis	1/12 (8.3%)	1
Soft tissue disorder	1/12 (8.3%)	1
Spinal osteoarthritis	2/12 (16.7%)	4
Spondylolisthesis	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma benign	1/12 (8.3%)	1
Nervous system disorders
Dizziness	1/12 (8.3%)	2
Extensor plantar response	1/12 (8.3%)	1
Headache	2/12 (16.7%)	3
Lethargy	1/12 (8.3%)	1
Migraine	1/12 (8.3%)	1
Nerve compression	2/12 (16.7%)	2
Paraesthesia	1/12 (8.3%)	1
Somnolence	2/12 (16.7%)	2
Syncope	1/12 (8.3%)	1
Transient ischaemic attack	1/12 (8.3%)	2
Psychiatric disorders
Anxiety	1/12 (8.3%)	1
Depression	1/12 (8.3%)	1
Renal and urinary disorders
Micturition urgency	1/12 (8.3%)	1
Renal cyst	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/12 (8.3%)	1
Respiratory disorder	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/12 (8.3%)	1
Vascular disorders
Aortic stenosis	1/12 (8.3%)	1
Hypertension	2/12 (16.7%)	2

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.