A Study to Evaluate the Effect of Romosozumab (AMG 785) on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00950950
• Collaborator: (none)
• Enrollment: 24
• Arms: 2
• Actual Duration (Months): 12

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of romosozumab on parameters of bone quality of the forearm using peripheral quantitative computed tomography (pQCT) following multiple subcutaneous dose administrations of romosozumab in postmenopausal women with low bone mass.

Condition or Disease	Intervention/Treatment	Phase
Osteopenia	Drug: Romosozumab; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate the Effect of AMG 785 on Parameters of Bone Quality of the Forearm Using pQCT in Postmenopausal Women With Low Bone Mineral Density
• Actual Study Start Date: Aug 18, 2009
• Actual Primary Completion Date: Aug 19, 2010
• Actual Study Completion Date: Aug 19, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Drug: Placebo; Administered by subcutaneous injection
Experimental: Romosozumab Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

Secondary Outcome Measures

1. Percent Change From Baseline in Total Bone Area at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

2. Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

3. Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

4. Percent Change From Baseline in Cortical Bone Area at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Cortical bone area was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

5. Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Cortical bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

6. Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Cortical bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

7. Percent Change From Baseline in Endocortical Circumference at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Endocortical circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

8. Percent Change From Baseline in Periosteal Circumference at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Periosteal circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

9. Percent Change From Baseline in Cortical Thickness at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

   Cortical thickness was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

10. Percent Change From Baseline in Polar Section Modulus at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Polar section modulus is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

11. Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

    The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

12. Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Axial moment of inertia is an indicator of the ability of bone to resist bending, and was derived from pQCT measurements based on a circular ring model. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

13. Percent Change From Baseline in Total Bone Area at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

14. Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

15. Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

16. Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Trabecular bone area was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

17. Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Trabecular bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

18. Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    Trabecular bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

19. Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius [Baseline and days 29, 57, 85, 127, and 169]

    The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

20. Percent Change From Baseline in Bone Mineral Density at the One-third Radius [Baseline and days 29, 57, 85, 127, and 169]

    Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.

21. Percent Change From Baseline in Bone Mineral Density at the Total Wrist [Baseline and days 29, 57, 85, 127, and 169]

    Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.

22. Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine [Baseline and days 85 and 169]

    Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.

23. Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) [Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169]

24. Percent Change From Baseline in Serum C-Telopeptide (sCTX) [Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169]

25. Time to Maximum Serum Concentration (Tmax) of Romosozumab [First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.

26. Maximum Serum Concentration (Cmax) of Romosozumab [First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.

27. Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28) [First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. The area under the serum drug concentration-time curve from time zero to tau (tau = 28 days) (AUC0-28) was calculated by the linear trapezoidal method.

28. Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) [Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.

29. Apparent Clearance (CL/F) of Romosozumab [Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.

30. Terminal Half-life (t1/2,z) of Romosozumab [Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.

31. Accumulation Ratio [First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169]

    Accumulation ratio was calculated as the ratio of AUC0-28 after the last dose to AUC0-28 after the first dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy females between 55 to 80 years of age

• Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea

• Women 60 years of age and older will be considered postmenopausal

• Women 55-59 must have a serum follicle-stimulating hormone result > 40 mIU/mL and serum estradiol ≤ 20 pg/mL

• Low bone mineral density (BMD), defined as a BMD T-score between -1.0 and -2.5 at the lumbar spine (L1-L4) and/or femoral neck

• Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)

• 25-hydroxyvitamin D ≥ 20 ng/mL at screening

• Willing and able to take ≥ 500 mg calcium and ≥ 400 IU (but ≤ 1,000 IU) vitamin D daily

Exclusion Criteria:

• Osteoporosis, defined as a BMD T-score ≤ -2.5 at the lumbar spine or femoral neck

• History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis

• Diagnosed with any condition that will affect bone metabolism

• Subjects with fewer than 2 evaluable vertebrae; metal in forearms bilaterally that would not allow for at least one evaluable forearm

• Administration of the following medications within 6 months before study drug administration. This includes all routes of administration, for example intranasal and topical skin patches, unless otherwise noted:

• Hormone replacement therapy [(eg, estrogen, estrogen-like compounds such as raloxifene). Infrequent use of estrogen vaginal creams (< 3 times per week) is allowed.]

• Calcitonin

• Parathyroid hormone (or any derivative)

• Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)

• Anabolic steroids

• Calcitriol, and available analogues

• Administration of daily, weekly, or monthly bisphosphonates (BP) unless meeting the following criteria:

• < 2 weeks of BP use requires a 2-month washout period

• 2 weeks to 3 months of BP use requires a 9-month washout period

• 3 to 6 months of BP use requires a 1-year washout period

• 6 months of BP use requires a 3-year washout period;

• Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration

• Known sensitivity to mammalian-derived drug preparations

• Known to be hepatitis B surface antigen, hepatitis C virus or human Immunodeficiency virus (HIV) positive or a known diagnosis of acquired immunodeficiency syndrome (AIDS)

• Any organic or psychiatric disorder, which, in the opinion of the investigator, poses a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results

• Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures

• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent

• History or evidence of a clinically significant disorder, condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

• Clinically significant abnormality during the screening physical examination, electrocardiogram (ECG) or laboratory evaluation

• Participation in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known

• Has donated or lost 400 mL or more of blood or plasma within 8 weeks of study drug administration

• Previous AMG 785 exposure

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00950950
• Other Study ID Numbers: 20090153
• First Posted: Aug 3, 2009
• Last Update Posted: Jul 5, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Amgen: Amgen; Postmenopausal; Bone Density
• Additional relevant MeSH terms: Bone Diseases, Metabolic

Study Results

Participant Flow

Recruitment Details	This study was conducted at a single center in the United States.
Pre-assignment Detail	Participants were equally randomized to receive romosozumab or placebo.

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Period Title: Overall Study
STARTED	12	12
COMPLETED	11	11
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Romosozumab	Total
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (5.6)	65.6 (7.2)	63.9 (6.5)
Age, Customized (Count of Participants)
18 - 64 years	9 75%	6 50%	15 62.5%
65 - 74 years	3 25%	4 33.3%	7 29.2%
≥ 75 years	0 0%	2 16.7%	2 8.3%
Sex: Female, Male (Count of Participants)
Female	12 100%	12 100%	24 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	12 100%	12 100%	24 100%
Polar Moment of Inertia (mm⁴) [Median (Full Range) ]
Median (Full Range) [mm⁴]	1545.14	1496.50	1501.96

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Description	The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-1.16 (1.40)	0.16 (0.95)
Day 57	-1.03 (1.00)	-1.03 (1.19)
Day 85	-2.28 (1.21)	1.45 (1.03)
Day 127	-1.93 (1.22)	0.87 (0.89)
Day 169	-1.66 (1.22)	-0.08 (1.12)

2. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Area at the Distal Radius
Description	Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.07 (0.56)	-0.21 (0.40)
Day 57	-0.08 (0.48)	-0.13 (0.56)
Day 85	-0.79 (0.49)	0.38 (0.61)
Day 127	0.05 (0.43)	0.87 (0.66)
Day 169	-0.23 (0.46)	-0.04 (0.70)

3. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Description	Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.39 (0.40)	-0.27 (0.41)
Day 57	-0.33 (0.37)	-0.49 (0.27)
Day 85	-0.86 (0.47)	-0.51 (0.36)
Day 127	-0.66 (0.36)	-0.43 (0.37)
Day 169	-1.34 (0.30)	-1.09 (0.36)

4. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Description	Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.30 (0.48)	-0.06 (0.30)
Day 57	-0.24 (0.38)	-0.34 (0.44)
Day 85	-0.07 (0.19)	-0.86 (0.53)
Day 127	-0.69 (0.48)	-1.26 (0.53)
Day 169	-0.10 (0.42)	-1.02 (0.55)

5. Secondary Outcome

Title	Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Description	Cortical bone area was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.27 (0.58)	0.06 (0.63)
Day 57	-0.05 (0.54)	-0.53 (0.64)
Day 85	-1.39 (0.77)	0.69 (0.67)
Day 127	-1.41 (0.81)	0.28 (0.63)
Day 169	-1.59 (0.58)	-0.50 (0.74)

6. Secondary Outcome

Title	Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Description	Cortical bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.33 (0.57)	0.07 (0.46)
Day 57	-0.29 (0.52)	-0.86 (0.45)
Day 85	-1.08 (0.66)	-0.07 (0.66)
Day 127	-1.45 (0.82)	-0.66 (0.57)
Day 169	-1.69 (0.55)	-1.29 (0.67)

7. Secondary Outcome

Title	Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Description	Cortical bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.06 (0.10)	0.02 (0.21)
Day 57	-0.24 (0.21)	-0.32 (0.28)
Day 85	0.32 (0.24)	-0.76 (0.23)
Day 127	-0.04 (0.23)	-0.92 (0.40)
Day 169	-0.10 (0.23)	-0.79 (0.31)

8. Secondary Outcome

Title	Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Description	Endocortical circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	0.20 (0.74)	-0.19 (0.50)
Day 57	-0.23 (0.73)	0.26 (0.67)
Day 85	-0.03 (0.39)	-0.07 (0.72)
Day 127	0.77 (0.80)	0.89 (0.66)
Day 169	0.85 (0.66)	0.49 (0.84)

9. Secondary Outcome

Title	Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Description	Periosteal circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.04 (0.28)	-0.11 (0.20)
Day 57	-0.04 (0.24)	-0.07 (0.28)
Day 85	-0.40 (0.25)	0.19 (0.31)
Day 127	0.02 (0.22)	0.43 (0.33)
Day 169	-0.12 (0.23)	-0.02 (0.35)

10. Secondary Outcome

Title	Percent Change From Baseline in Cortical Thickness at the Distal Radius
Description	Cortical thickness was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.29 (0.82)	0.22 (0.77)
Day 57	0.09 (0.79)	-0.56 (0.85)
Day 85	-1.14 (0.72)	0.64 (0.99)
Day 127	-1.69 (1.14)	-0.31 (0.80)
Day 169	-1.82 (0.78)	-0.62 (1.09)

11. Secondary Outcome

Title	Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Description	Polar section modulus is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	0.18 (0.78)	0.02 (0.78)
Day 57	-0.11 (1.08)	-0.46 (1.05)
Day 85	-2.14 (1.40)	0.93 (1.22)
Day 127	-2.31 (1.55)	1.76 (1.32)
Day 169	-1.67 (1.14)	-1.05 (1.20)

12. Secondary Outcome

Title	Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Description	The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-1.85 (0.81)	-0.78 (0.51)
Day 57	-1.32 (0.75)	-1.47 (1.21)
Day 85	0.36 (0.99)	-1.91 (1.49)
Day 127	-0.71 (0.95)	-1.57 (0.94)
Day 169	-0.41 (0.98)	-1.25 (0.78)

13. Secondary Outcome

Title	Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Description	Axial moment of inertia is an indicator of the ability of bone to resist bending, and was derived from pQCT measurements based on a circular ring model. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.22 (0.91)	-0.23 (0.73)
Day 57	-0.19 (0.74)	-0.49 (0.88)
Day 85	-1.90 (1.09)	0.94 (0.83)
Day 127	-0.90 (0.65)	1.41 (1.04)
Day 169	-1.25 (0.75)	-0.28 (0.98)

14. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Description	Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-2.30 (3.64)	-0.72 (2.35)
Day 57	-5.11 (2.44)	-0.01 (3.66)
Day 85	-0.27 (2.37)	7.35 (3.21)
Day 127	-0.43 (2.46)	3.27 (2.96)
Day 169	1.90 (2.50)	0.91 (3.32)

15. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Description	Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	0.63 (0.43)	-0.30 (0.70)
Day 57	0.13 (0.53)	-0.09 (0.63)
Day 85	0.63 (0.56)	1.16 (0.39)
Day 127	0.46 (0.56)	-0.14 (0.46)
Day 169	0.15 (0.59)	-0.64 (0.97)

16. Secondary Outcome

Title	Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Description	Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	4.45 (4.42)	0.91 (1.97)
Day 57	6.22 (3.19)	1.19 (2.98)
Day 85	1.52 (2.64)	-4.95 (2.33)
Day 127	1.43 (2.35)	-2.53 (2.38)
Day 169	-1.14 (2.72)	-0.81 (2.59)

17. Secondary Outcome

Title	Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Description	Trabecular bone area was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-3.54 (5.68)	-0.64 (3.59)
Day 57	-8.06 (3.86)	0.43 (6.21)
Day 85	-0.55 (3.82)	12.00 (5.84)
Day 127	-1.86 (4.01)	5.60 (5.22)
Day 169	2.84 (4.18)	1.57 (5.20)

18. Secondary Outcome

Title	Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Description	Trabecular bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-3.26 (7.35)	-0.52 (4.78)
Day 57	-9.52 (4.68)	0.02 (7.61)
Day 85	1.02 (5.51)	14.64 (7.06)
Day 127	-0.70 (6.15)	5.68 (6.54)
Day 169	5.12 (5.55)	1.74 (6.71)

19. Secondary Outcome

Title	Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Description	Trabecular bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	-0.78 (1.88)	-0.34 (1.33)
Day 57	-1.98 (1.16)	-1.30 (1.59)
Day 85	0.98 (1.64)	2.00 (0.88)
Day 127	0.53 (1.92)	-0.49 (1.19)
Day 169	1.74 (1.47)	-0.51 (1.64)

20. Secondary Outcome

Title	Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Description	The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	2.69 (2.36)	-0.14 (1.00)
Day 57	2.28 (1.47)	1.28 (2.06)
Day 85	1.08 (1.71)	-0.90 (2.30)
Day 127	-0.87 (1.29)	-0.89 (1.95)
Day 169	-0.25 (1.61)	-1.51 (1.86)

21. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Description	Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	1.715 (0.808)	1.210 (0.814)
Day 57	0.832 (1.155)	-0.694 (0.827)
Day 85	0.790 (1.117)	-1.941 (0.986)
Day 127	-0.118 (1.405)	-0.439 (1.346)
Day 169	1.866 (0.905)	-0.328 (0.702)

22. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Description	Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Time Frame	Baseline and days 29, 57, 85, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 29	1.829 (0.617)	-0.555 (0.428)
Day 57	0.940 (1.081)	-1.651 (0.574)
Day 85	0.233 (0.996)	-1.690 (0.733)
Day 127	0.001 (1.081)	-0.369 (0.765)
Day 169	0.357 (1.237)	-0.649 (0.522)

23. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine
Description	Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Time Frame	Baseline and days 85 and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 85	0.345 (1.224)	4.786 (0.846)
Day 169	0.149 (0.905)	7.876 (1.351)

24. Secondary Outcome

Title	Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Time Frame	Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 4	-4.40 (6.13)	36.37 (10.02)
Day 15	3.46 (5.64)	146.39 (20.00)
Day 29	-0.33 (3.44)	101.85 (19.97)
Day 57	-6.93 (4.52)	74.77 (10.91)
Day 62	0.27 (9.20)	92.22 (14.71)
Day 71	19.61 (16.22)	106.91 (14.08)
Day 85	23.83 (17.11)	67.85 (19.11)
Day 99	10.94 (15.57)	17.07 (11.79)
Day 127	5.49 (10.26)	12.56 (8.57)
Day 169	20.85 (10.44)	33.80 (13.64)

25. Secondary Outcome

Title	Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Time Frame	Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

Treated participants with available data at each time point

Arm/Group Title	Placebo	Romosozumab
Arm/Group Description	Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12	12
Day 4	6.62 (4.33)	-23.77 (7.78)
Day 15	-2.29 (5.15)	-33.10 (8.85)
Day 29	-3.19 (8.83)	-21.42 (13.98)
Day 57	7.87 (6.49)	7.26 (16.28)
Day 62	8.69 (5.78)	-12.67 (15.15)
Day 71	5.60 (5.59)	-14.72 (13.84)
Day 85	-3.00 (7.94)	4.85 (19.28)
Day 99	-9.14 (8.17)	14.29 (23.73)
Day 127	-10.00 (8.91)	6.32 (16.60)
Day 169	-3.61 (8.95)	16.06 (20.53)

26. Secondary Outcome

Title	Time to Maximum Serum Concentration (Tmax) of Romosozumab
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12
First dose	3.0
Last dose	5.0

27. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Romosozumab
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12
First dose	26.8 (6.4)
Last dose	32.3 (9.6)

28. Secondary Outcome

Title	Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28)
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. The area under the serum drug concentration-time curve from time zero to tau (tau = 28 days) (AUC0-28) was calculated by the linear trapezoidal method.
Time Frame	First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	12
First dose	422 (75)
Last dose	501 (179)

29. Secondary Outcome

Title	Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf)
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	11
Mean (Standard Deviation) [μg*day/mL]	590 (240)

30. Secondary Outcome

Title	Apparent Clearance (CL/F) of Romosozumab
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	11
Mean (Standard Deviation) [mL/day/kg]	5.82 (2.12)

31. Secondary Outcome

Title	Terminal Half-life (t1/2,z) of Romosozumab
Description	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Time Frame	Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	11
Mean (Standard Deviation) [days]	6.82 (0.92)

32. Secondary Outcome

Title	Accumulation Ratio
Description	Accumulation ratio was calculated as the ratio of AUC0-28 after the last dose to AUC0-28 after the first dose.
Time Frame	First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169

Outcome Measure Data

Analysis Population Description

All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated

Arm/Group Title	Romosozumab
Arm/Group Description	Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
Measure Participants	11
Mean (Standard Deviation) [ratio]	1.15 (0.27)

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Placebo		Romosozumab
Arm/Group Description	Participants received matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.		Participants received 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
All Cause Mortality
	Placebo		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		1/12 (8.3%)
Gastrointestinal disorders
Gastrointestinal ulcer haemorrhage	0/12 (0%)		1/12 (8.3%)
Infections and infestations
Arthritis infective	0/12 (0%)		1/12 (8.3%)
Nervous system disorders
Cauda equina syndrome	1/12 (8.3%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		10/12 (83.3%)
Blood and lymphatic system disorders
Anaemia	1/12 (8.3%)		0/12 (0%)
Gastrointestinal disorders
Abdominal distension	1/12 (8.3%)		0/12 (0%)
Constipation	2/12 (16.7%)		1/12 (8.3%)
Dyspepsia	1/12 (8.3%)		0/12 (0%)
Dysphagia	1/12 (8.3%)		0/12 (0%)
Enteritis	1/12 (8.3%)		0/12 (0%)
Nausea	1/12 (8.3%)		0/12 (0%)
General disorders
Chest pain	1/12 (8.3%)		1/12 (8.3%)
Injection site discomfort	1/12 (8.3%)		0/12 (0%)
Injection site reaction	2/12 (16.7%)		1/12 (8.3%)
Injection site swelling	0/12 (0%)		1/12 (8.3%)
Oedema peripheral	0/12 (0%)		2/12 (16.7%)
Pyrexia	0/12 (0%)		1/12 (8.3%)
Vessel puncture site haematoma	1/12 (8.3%)		0/12 (0%)
Infections and infestations
Nasopharyngitis	0/12 (0%)		1/12 (8.3%)
Sinusitis	1/12 (8.3%)		0/12 (0%)
Upper respiratory tract infection	0/12 (0%)		1/12 (8.3%)
Urinary tract infection	2/12 (16.7%)		0/12 (0%)
Injury, poisoning and procedural complications
Anaemia postoperative	0/12 (0%)		1/12 (8.3%)
Joint sprain	1/12 (8.3%)		0/12 (0%)
Procedural nausea	0/12 (0%)		1/12 (8.3%)
Scratch	1/12 (8.3%)		0/12 (0%)
Thermal burn	0/12 (0%)		1/12 (8.3%)
Tooth fracture	0/12 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Hypokalaemia	0/12 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/12 (25%)		1/12 (8.3%)
Back pain	1/12 (8.3%)		1/12 (8.3%)
Jaw disorder	0/12 (0%)		1/12 (8.3%)
Musculoskeletal pain	2/12 (16.7%)		1/12 (8.3%)
Myalgia	1/12 (8.3%)		0/12 (0%)
Osteoarthritis	1/12 (8.3%)		1/12 (8.3%)
Pain in extremity	1/12 (8.3%)		1/12 (8.3%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/12 (0%)
Dizziness postural	0/12 (0%)		1/12 (8.3%)
Headache	0/12 (0%)		1/12 (8.3%)
Migraine	1/12 (8.3%)		0/12 (0%)
Presyncope	1/12 (8.3%)		0/12 (0%)
Reproductive system and breast disorders
Breast tenderness	0/12 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/12 (0%)		1/12 (8.3%)
Dyspnoea exertional	1/12 (8.3%)		0/12 (0%)
Nasal congestion	1/12 (8.3%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Ecchymosis	0/12 (0%)		1/12 (8.3%)
Ingrowing nail	0/12 (0%)		1/12 (8.3%)
Onychoclasis	0/12 (0%)		1/12 (8.3%)
Pruritus	1/12 (8.3%)		0/12 (0%)
Rash macular	1/12 (8.3%)		0/12 (0%)
Vascular disorders
Hypertension	2/12 (16.7%)		2/12 (16.7%)
Thrombophlebitis superficial	0/12 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.