Postmenopausal Osteoporosis (PMO)
Conditions
Keywords
Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
Brief summary
The purpose of this study is to determine if treatment with romosozumab increases bone mineral density in Japanese women with postmenopausal osteoporosis.
Interventions
DRUGRomosozumab
Administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Ambulatory, postmenopausal Japanese women with osteoporosis (defined as bone mineral density T-score of ≤ -4.00 at the lumbar spine or BMD T-score of ≤ -3.50 at the total hip, or femoral neck)
Exclusion criteria
* Severe osteoporosis * Use of agents affecting bone metabolism * History of metabolic or bone disease (except osteoporosis) * Vitamin D insufficiency (vitamin D repletion and rescreening is permitted) * Current hyper- or hypocalcemia * Current, uncontrolled hyper- or hypothyroidism * Current, uncontrolled hyper- or hypoparathyroidism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine | Baseline and 12 months | Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip | Baseline and 6 months | Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
| Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip | Baseline and 12 months | Bone density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
| Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck | Baseline and 6 months | Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
| Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck | Baseline and 12 months | Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
| Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine | Baseline and 6 months | Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader. |
| Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Baseline, week 1, and months 1, 2, 3, 6, 9, and 12 | — |
| Percent Change From Baseline in Osteocalcin | Baseline, week 1, and months 1, 2, 3, 6, 9, and 12 | — |
| Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Baseline, week 1, and months 1, 2, 3, 6, 9, and 12 | — |
| Area Under the Curve Through Month 12 of P1NP | Baseline, week 1 and months 1, 2, 3, 6, 9, and 12. | — |
| Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Baseline, week 1, and months 1, 2, 3, 6, 9, and 12 | — |
Countries
Japan
Participant flow
Recruitment details
This study was conducted at 24 centers in Japan. The first participant was enrolled on 12 October 2012 and the last participant enrolled on 15 October 2013.
Pre-assignment details
Participants were randomized in a 1:1:1:1 ratio to receive placebo or romosozumab 70, 140, or 210 mg subcutaneous (SC) injection every month (QM) for 12 months. Upon completion of the 12-month treatment period, participants were followed for another 3 months for assessment of antiromosozumab antibody formation (follow-up period).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months. | 63 |
| Romosozumab 70 mg Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months. | 63 |
| Romosozumab 140 mg Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months. | 63 |
| Romosozumab 210 mg Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months. | 63 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 7 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Romosozumab 70 mg | Romosozumab 140 mg | Romosozumab 210 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.8 years STANDARD_DEVIATION 7.2 | 66.5 years STANDARD_DEVIATION 6.3 | 68.4 years STANDARD_DEVIATION 6 | 68.3 years STANDARD_DEVIATION 5.9 | 67.7 years STANDARD_DEVIATION 6.4 |
| Age, Customized ≥ 65 to < 75 years | 22 Participants | 22 Participants | 34 Participants | 34 Participants | 112 Participants |
| Age, Customized < 65 years | 27 Participants | 30 Participants | 18 Participants | 18 Participants | 93 Participants |
| Age, Customized ≥ 75 years | 14 Participants | 11 Participants | 11 Participants | 11 Participants | 47 Participants |
| Bone Specific Alkaline Phosphatase (BSAP) | 14.49 μg/L | 13.92 μg/L | 15.49 μg/L | 14.72 μg/L | 14.72 μg/L |
| Femoral Neck BMD T-score | -2.31 T-score STANDARD_DEVIATION 0.47 | -2.27 T-score STANDARD_DEVIATION 0.53 | -2.28 T-score STANDARD_DEVIATION 0.65 | -2.32 T-score STANDARD_DEVIATION 0.59 | -2.29 T-score STANDARD_DEVIATION 0.56 |
| Lumbar Spine Bone Mineral Density (BMD) T-score | -2.69 T-score STANDARD_DEVIATION 0.52 | -2.73 T-score STANDARD_DEVIATION 0.57 | -2.65 T-score STANDARD_DEVIATION 0.66 | -2.72 T-score STANDARD_DEVIATION 0.42 | -2.70 T-score STANDARD_DEVIATION 0.54 |
| Osteocalcin | 22.17 μg/L | 22.50 μg/L | 21.01 μg/L | 22.75 μg/L | 22.03 μg/L |
| Race/Ethnicity, Customized Asian | 63 Participants | 63 Participants | 63 Participants | 63 Participants | 252 Participants |
| Serum Procollagen Type 1 N-telopeptide (P1NP) | 52.4 μg/L | 51.9 μg/L | 47.6 μg/L | 50.9 μg/L | 50.5 μg/L |
| Serum Type 1 Collagen C-telopeptide (CTX) | 441.0 ng/L | 441.0 ng/L | 374.0 ng/L | 420.0 ng/L | 412.0 ng/L |
| Sex: Female, Male Female | 63 Participants | 63 Participants | 63 Participants | 63 Participants | 252 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Hip BMD T-score | -2.00 T-score STANDARD_DEVIATION 0.6 | -1.97 T-score STANDARD_DEVIATION 0.57 | -1.85 T-score STANDARD_DEVIATION 0.68 | -1.95 T-score STANDARD_DEVIATION 0.65 | -1.94 T-score STANDARD_DEVIATION 0.63 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 63 | 33 / 63 | 29 / 63 | 32 / 63 |
| serious Total, serious adverse events | 5 / 63 | 6 / 63 | 3 / 63 | 2 / 63 |
Outcome results
Primary
Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine
Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 12 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement (primary efficacy subset).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine | 0.9 percent change |
| Romosozumab 70 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine | 8.4 percent change |
| Romosozumab 140 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine | 13.3 percent change |
| Romosozumab 210 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine | 16.9 percent change |
Comparison: The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Secondary
Area Under the Curve Through Month 12 of P1NP
Time frame: Baseline, week 1 and months 1, 2, 3, 6, 9, and 12.
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, had never received any dose of incorrect treatment, and had no missing P1NP measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Area Under the Curve Through Month 12 of P1NP | 554.5 ug*month/L |
| Romosozumab 70 mg | Area Under the Curve Through Month 12 of P1NP | 539.2 ug*month/L |
| Romosozumab 140 mg | Area Under the Curve Through Month 12 of P1NP | 638.5 ug*month/L |
| Romosozumab 210 mg | Area Under the Curve Through Month 12 of P1NP | 708.3 ug*month/L |
p-value: 0.508495% CI: [-60.8, 30.2]ANCOVA
p-value: 0.000295% CI: [40.1, 128]ANCOVA
p-value: <0.000195% CI: [109.2, 198.4]ANCOVA
Secondary
Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine
Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 6 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine | 1.2 percent change |
| Romosozumab 70 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine | 6.5 percent change |
| Romosozumab 140 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine | 10.2 percent change |
| Romosozumab 210 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine | 13.1 percent change |
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Secondary
Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip
Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 6 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip | 0.6 percent change |
| Romosozumab 70 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip | 1.2 percent change |
| Romosozumab 140 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip | 2.3 percent change |
| Romosozumab 210 mg | Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip | 3.2 percent change |
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.125Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.0002Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Secondary
Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP)
Time frame: Baseline, week 1, and months 1, 2, 3, 6, 9, and 12
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Week 1 | 1.6 percent change | Standard Deviation 13.4 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 9 | -7.0 percent change | Standard Deviation 20.5 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 6 | -6.6 percent change | Standard Deviation 20.5 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 1 | -0.5 percent change | Standard Deviation 22.1 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 12 | -6.3 percent change | Standard Deviation 22.7 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 2 | -7.8 percent change | Standard Deviation 16.9 |
| Placebo | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 3 | -9.5 percent change | Standard Deviation 16.3 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 9 | -10.7 percent change | Standard Deviation 21.7 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 3 | -2.8 percent change | Standard Deviation 14.9 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 2 | 8.7 percent change | Standard Deviation 20.8 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 6 | -9.0 percent change | Standard Deviation 19 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 12 | -13.2 percent change | Standard Deviation 19.9 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 1 | 23.0 percent change | Standard Deviation 19.9 |
| Romosozumab 70 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Week 1 | 14.0 percent change | Standard Deviation 14.5 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 3 | 23.5 percent change | Standard Deviation 26.5 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Week 1 | 17.0 percent change | Standard Deviation 16.4 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 1 | 51.3 percent change | Standard Deviation 27.6 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 2 | 31.8 percent change | Standard Deviation 27.9 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 6 | 3.1 percent change | Standard Deviation 21.6 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 9 | -2.6 percent change | Standard Deviation 25.3 |
| Romosozumab 140 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 12 | -13.7 percent change | Standard Deviation 23.3 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 2 | 55.1 percent change | Standard Deviation 31 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 12 | -9.3 percent change | Standard Deviation 21.4 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 9 | 3.5 percent change | Standard Deviation 23.8 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 1 | 66.2 percent change | Standard Deviation 31.9 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Week 1 | 20.1 percent change | Standard Deviation 17.9 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 6 | 13.2 percent change | Standard Deviation 26.8 |
| Romosozumab 210 mg | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) | Month 3 | 39.6 percent change | Standard Deviation 33.2 |
Secondary
Percent Change From Baseline in Osteocalcin
Time frame: Baseline, week 1, and months 1, 2, 3, 6, 9, and 12
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Osteocalcin | Week 1 | 2.6 percent change | Standard Deviation 18.1 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 9 | -8.4 percent change | Standard Deviation 18.2 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 6 | -10.3 percent change | Standard Deviation 15.9 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 1 | -3.8 percent change | Standard Deviation 12.7 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 12 | -6.8 percent change | Standard Deviation 20.6 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 2 | -7.0 percent change | Standard Deviation 13.4 |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 3 | -7.2 percent change | Standard Deviation 16.8 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 9 | -6.8 percent change | Standard Deviation 22.5 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 3 | 4.9 percent change | Standard Deviation 17.5 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 2 | 13.7 percent change | Standard Deviation 15.1 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 6 | -5.5 percent change | Standard Deviation 18.8 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 12 | -8.6 percent change | Standard Deviation 21.8 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Month 1 | 26.5 percent change | Standard Deviation 20.4 |
| Romosozumab 70 mg | Percent Change From Baseline in Osteocalcin | Week 1 | 6.5 percent change | Standard Deviation 12.6 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 3 | 28.4 percent change | Standard Deviation 29.7 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Week 1 | 7.9 percent change | Standard Deviation 17 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 1 | 51.2 percent change | Standard Deviation 31.9 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 2 | 39.3 percent change | Standard Deviation 31.6 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 6 | 10.6 percent change | Standard Deviation 24.7 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 9 | -0.9 percent change | Standard Deviation 24 |
| Romosozumab 140 mg | Percent Change From Baseline in Osteocalcin | Month 12 | -9.4 percent change | Standard Deviation 22.1 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 2 | 48.9 percent change | Standard Deviation 31.6 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 12 | -8.9 percent change | Standard Deviation 17.9 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 9 | -1.3 percent change | Standard Deviation 18.9 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 1 | 66.4 percent change | Standard Deviation 31.3 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Week 1 | 5.5 percent change | Standard Deviation 14.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 6 | 9.3 percent change | Standard Deviation 19.2 |
| Romosozumab 210 mg | Percent Change From Baseline in Osteocalcin | Month 3 | 27.5 percent change | Standard Deviation 22.3 |
Secondary
Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
Time frame: Baseline, week 1, and months 1, 2, 3, 6, 9, and 12
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -8.9 percent change | Standard Deviation 23.3 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 2 | -10.9 percent change | Standard Deviation 18.5 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | 4.6 percent change | Standard Deviation 37.9 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -11.5 percent change | Standard Deviation 20.3 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -2.1 percent change | Standard Deviation 32 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Week 1 | -2.5 percent change | Standard Deviation 9 |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | -5.7 percent change | Standard Deviation 22.1 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -16.9 percent change | Standard Deviation 31.3 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -11.1 percent change | Standard Deviation 29.8 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 32.2 percent change | Standard Deviation 22.9 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 2 | -0.7 percent change | Standard Deviation 18.4 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Week 1 | 43.4 percent change | Standard Deviation 24 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -13.1 percent change | Standard Deviation 18.3 |
| Romosozumab 70 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -16.8 percent change | Standard Deviation 26 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | 14.9 percent change | Standard Deviation 32.2 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Week 1 | 65.9 percent change | Standard Deviation 25.7 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 79.8 percent change | Standard Deviation 41.7 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -9.1 percent change | Standard Deviation 30.9 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -2.7 percent change | Standard Deviation 28 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 2 | 34.6 percent change | Standard Deviation 38.2 |
| Romosozumab 140 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -16.2 percent change | Standard Deviation 27.4 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -13.1 percent change | Standard Deviation 28.1 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Week 1 | 81.5 percent change | Standard Deviation 34.6 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 2 | 59.8 percent change | Standard Deviation 40.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | 25.5 percent change | Standard Deviation 33.4 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | 2.4 percent change | Standard Deviation 24.8 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -4.0 percent change | Standard Deviation 31.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 101.6 percent change | Standard Deviation 41.1 |
Secondary
Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
Time frame: Baseline, week 1, and months 1, 2, 3, 6, 9, and 12
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Week 1 | 11.9 percent change | Standard Deviation 27.8 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | 12.6 percent change | Standard Deviation 56.6 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | 13.6 percent change | Standard Deviation 49.8 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | 14.9 percent change | Standard Deviation 40.2 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | 35.4 percent change | Standard Deviation 81.7 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 2 | 14.1 percent change | Standard Deviation 41.6 |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | 16.1 percent change | Standard Deviation 49 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -13.2 percent change | Standard Deviation 53 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -5.5 percent change | Standard Deviation 48.3 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 2 | -2.3 percent change | Standard Deviation 48.4 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -10.8 percent change | Standard Deviation 52.2 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -4.1 percent change | Standard Deviation 47.2 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -18.0 percent change | Standard Deviation 34.3 |
| Romosozumab 70 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Week 1 | -28.0 percent change | Standard Deviation 25.8 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | 28.9 percent change | Standard Deviation 84.1 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Week 1 | -32.1 percent change | Standard Deviation 32.8 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -8.0 percent change | Standard Deviation 53.9 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 2 | 14.9 percent change | Standard Deviation 67.8 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | 3.2 percent change | Standard Deviation 71.8 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -8.0 percent change | Standard Deviation 55.7 |
| Romosozumab 140 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | 2.1 percent change | Standard Deviation 73.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 2 | 0.1 percent change | Standard Deviation 49.1 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -10.5 percent change | Standard Deviation 53.8 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -15.3 percent change | Standard Deviation 44.8 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -24.6 percent change | Standard Deviation 30.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Week 1 | -42.0 percent change | Standard Deviation 25.4 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -13.4 percent change | Standard Deviation 40.6 |
| Romosozumab 210 mg | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | 8.1 percent change | Standard Deviation 53.8 |
Secondary
Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck
Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 12 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck | 0.3 percent change |
| Romosozumab 70 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck | 1.9 percent change |
| Romosozumab 140 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck | 2.9 percent change |
| Romosozumab 210 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck | 3.8 percent change |
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.0067Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Secondary
Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip
Bone density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 12 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip | 0.6 percent change |
| Romosozumab 70 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip | 2.1 percent change |
| Romosozumab 140 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip | 3.2 percent change |
| Romosozumab 210 mg | Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip | 4.7 percent change |
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.0012Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: <0.0001Repeated Measures Model
Secondary
Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck
Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time frame: Baseline and 6 months
Population: Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck | 0.6 percent change |
| Romosozumab 70 mg | Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck | 1.0 percent change |
| Romosozumab 140 mg | Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck | 1.9 percent change |
| Romosozumab 210 mg | Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck | 3.3 percent change |
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.2846Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.0151Repeated Measures Model
Comparison: The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.p-value: 0.0001Repeated Measures Model