Postmenopausal Women With Osteoporosis
Conditions
Keywords
Osteoporosis, Osteoporosis-postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
Brief summary
The purpose of this study is to determine if treatment is effective in preventing fractures in women with postmenopausal osteoporosis.
Detailed description
In this trial, women were randomly assigned in a 1:1 ratio to receive monthly subcutaneous romosozumab or weekly oral alendronate for 12 months. Randomization was stratified according to age (\<75 vs. ≥75 years). After completion of the double-blind treatment period, all the participants were to receive open-label weekly oral alendronate until the end of the trial, with blinding to the initial treatment assignment maintained. The primary analysis was performed when clinical fracture events had been confirmed in at least 330 participants and all the participants had completed the month 24 visit. The study was to continue in an event-driven manner until at least 440 participants experienced a nonvertebral fracture or if the superiority of romosozumab was proven for nonvertebral fractures at the primary analysis.
Interventions
BIOLOGICALRomosozumab
Romosozumab 210 mg administered by subcutaneous injection once a month during the double-blind treatment phase.
DRUGAlendronate
Alendronate 70 mg tablet taken once a week
Administered by subcutaneous injection once a month during the double-blind treatment phase.
Matching placebo tablet taken once a week during the double-blind treatment phase.
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 90 Years
Healthy volunteers
No
Inclusion criteria
Postmenopausal women who meet at least one of the following bone mineral density (BMD) and fracture criteria: * BMD T-score at the total hip or femoral neck of ≤ -2.50 and EITHER: * at least 1 moderate (semiquantitative grade \[SQ\]2) or severe (SQ3) vertebral fracture OR * at least 2 mild (SQ1) vertebral fractures OR * BMD T-score at the total hip or femoral neck of ≤ -2.00 and EITHER: * at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR * a fracture of the proximal femur that occurred within 3 to 24 months prior to randomization.
Exclusion criteria
* History of metabolic or bone disease (except osteoporosis) * Use of agents affecting bone metabolism * Vitamin D insufficiency * History of solid organ or bone marrow transplants * Hyper- or hypocalcemia * Hyper- or hypothyroidism * Hyper- or hypoparathyroidism * Possible signs of intolerance to alendronate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With New Vertebral Fractures Through Month 24 | 24 months | All fracture assessments were performed by blinded central imaging readers. New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method. |
| Percentage of Participants With a Clinical Fracture at the Primary Analysis | The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). | All fracture assessments were performed by blinded central imaging readers. Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24 | 24 months | A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4 according to the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method. |
| Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis | The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). | Major nonvertebral fractures included a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip. |
| Percentage of Participants With a Hip Fracture at the Primary Analysis | The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). | Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. |
| Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24 | 24 months | A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4 according to the Genant Semiquantitative Scoring method. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. Incident vertebral fractures were confirmed by a second independent reader. |
| Percentage of Participants With a Clinical Fracture Through Month 24 | 24 months | Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With a Nonvertebral Fracture Through Month 24 | 24 months | A nonvertebral fracture was defined as a documented fracture excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With a Hip Fracture Through Month 24 | 24 months | Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. |
| Percentage of Participants With a Clinical Vertebral Fracture Through Month 24 | 24 months | A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic. |
| Percentage of Participants With a Clinical Fracture Through Month 12 | 12 months | Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With New Vertebral Fractures Through Month 12 | 12 months | New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader. |
| Percentage of Participants With Any Fracture Through Month 12 | 12 months | All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures. |
| Percentage of Participants With a Nonvertebral Fracture Through Month 12 | 12 months | A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis | The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). | A nonvertebral fracture was defined as a documented fracture excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With a Major Osteoporotic Fracture Through Month 12 | 12 months | Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded. |
| Percentage of Participants With a Clinical Vertebral Fracture Through Month 12 | 12 months | A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic. |
| Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24 | Baseline and month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24 | Baseline and month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24 | Baseline and month 24 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12 | Baseline and month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12 | Baseline and month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12 | Baseline and month 12 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36 | Baseline and month 36 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36 | Baseline and month 36 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36 | Baseline and month 36 | Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percentage of Participants With a Hip Fracture Through Month 12 | 12 months | Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter. |
| Percentage of Participants With Any Fracture at the Primary Analysis | The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3). | All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czechia, Denmark, Dominican Republic, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 270 centers in 41 countries globally from 04 May 2012 to 29 June 2017.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive romosozumab or alendronate for 12 months. Randomization was stratified by age (\< 75 vs. ≥ 75 years). After completion of the double-blind trial period, all participants received open-label alendronate until the end of the trial, with blinding to the initial treatment assignment maintained.
Participants by arm
| Arm | Count |
|---|---|
| Alendronate/Alendronate Participants received 70 mg alendronate once a week and placebo to romosozumab subcutaneously once a month for the first 12 months. After completion of the 12-month double-blind treatment period participants continued to receive 70 mg alendronate once a week until the end of the study. | 2,047 |
| Romosozumab/Alendronate Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study. | 2,046 |
| Total | 4,093 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 1 | 0 |
| Overall Study | Adverse Event | 45 | 45 |
| Overall Study | Death | 113 | 106 |
| Overall Study | Ineligibility determined | 5 | 2 |
| Overall Study | Lost to Follow-up | 54 | 40 |
| Overall Study | Noncompliance | 16 | 15 |
| Overall Study | Other | 22 | 19 |
| Overall Study | Protocol Deviation | 4 | 3 |
| Overall Study | Requirement for Alternative Therapy | 8 | 3 |
| Overall Study | Withdrawal by Subject | 276 | 290 |
Baseline characteristics
| Characteristic | Romosozumab/Alendronate | Total | Alendronate/Alendronate |
|---|---|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 7.5 | 74.3 years STANDARD_DEVIATION 7.5 | 74.2 years STANDARD_DEVIATION 7.5 |
| Age Strata per Randomization < 75 years | 973 Participants | 1949 Participants | 976 Participants |
| Age Strata per Randomization ≥ 75 years | 1073 Participants | 2144 Participants | 1071 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 631 Participants | 1293 Participants | 662 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1415 Participants | 2800 Participants | 1385 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants | 12 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 137 Participants | 286 Participants | 149 Participants |
| Race/Ethnicity, Customized Black or African American | 19 Participants | 42 Participants | 23 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 436 Participants | 882 Participants | 446 Participants |
| Race/Ethnicity, Customized White | 1447 Participants | 2862 Participants | 1415 Participants |
| Severe Vertebral Fracture Absence | 677 Participants | 1403 Participants | 726 Participants |
| Severe Vertebral Fracture Presence | 1369 Participants | 2690 Participants | 1321 Participants |
| Sex: Female, Male Female | 2046 Participants | 4093 Participants | 2047 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Total Hip Bone Mineral Density (BMD) T-score ≤ -2.5 | 1356 Participants | 2740 Participants | 1384 Participants |
| Total Hip Bone Mineral Density (BMD) T-score > -2.5 | 690 Participants | 1352 Participants | 662 Participants |
| Total Hip Bone Mineral Density (BMD) T-score Missing | 0 Participants | 1 Participants | 1 Participants |
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 | 22 / 2,014 | 30 / 2,040 | 103 / 2,014 | 101 / 2,040 |
| other Total, other adverse events | 1,190 / 2,014 | 1,112 / 2,040 | 1,498 / 2,014 | 1,424 / 2,040 |
| serious Total, serious adverse events | 278 / 2,014 | 262 / 2,040 | 638 / 2,014 | 611 / 2,040 |
Outcome results
Primary
Percentage of Participants With a Clinical Fracture at the Primary Analysis
All fracture assessments were performed by blinded central imaging readers. Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
Population: All randomized participants. Missing values for clinical fractures were imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Clinical Fracture at the Primary Analysis | 13.0 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Clinical Fracture at the Primary Analysis | 9.7 percentage of participants |
p-value: <0.00195% CI: [0.61, 0.88]Regression, Cox
Primary
Percentage of Participants With New Vertebral Fractures Through Month 24
All fracture assessments were performed by blinded central imaging readers. New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method.
Time frame: 24 months
Population: Randomized participants with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture, including participants who had vertebrae with missing Genant semiquantitative scores at baseline whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With New Vertebral Fractures Through Month 24 | 8.0 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With New Vertebral Fractures Through Month 24 | 4.1 percentage of participants |
p-value: <0.00195% CI: [0.36, 0.64]Regression, Logistic
Comparison: The risk ratio (ratio of percentages, Romosozumab:Alendronate) was based on the Mantel Haenszel method, adjusted for age strata (\<75 vs. ≥75 years), the presence or absence of severe vertebral fracture at baseline, and baseline bone mineral density T-score at the total hip (≤ -2.5, \> -2.5).~Values \< 1 for risk ratio favor romosozumab.95% CI: [0.38, 0.66]
Comparison: The absolute risk reduction (difference in percentages, Alendronate - Romosozumab) was based on the Mantel-Haenszel method adjusted for age strata, baseline total hip BMD T-score (≤ -2.5, \> -2.5), and presence of severe vertebral fracture at baseline.~Positive values for absolute risk reduction favor romosozumab.95% CI: [2.5, 5.57]
Secondary
Percentage of Participants With a Clinical Fracture Through Month 12
Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: 12 months
Population: All randomized participants; Missing values for clinical fractures were imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Clinical Fracture Through Month 12 | 5.4 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Clinical Fracture Through Month 12 | 3.9 percentage of participants |
p-value: 0.02795% CI: [0.54, 0.96]Regression, Cox
Secondary
Percentage of Participants With a Clinical Fracture Through Month 24
Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: 24 months
Population: All randomized participants; Missing values for clinical fractures were imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Clinical Fracture Through Month 24 | 9.6 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Clinical Fracture Through Month 24 | 7.1 percentage of participants |
p-value: 0.00595% CI: [0.59, 0.91]Regression, Cox
Secondary
Percentage of Participants With a Clinical Vertebral Fracture Through Month 12
A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic.
Time frame: 12 months
Population: All randomized participants; Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Clinical Vertebral Fracture Through Month 12 | 0.9 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Clinical Vertebral Fracture Through Month 12 | 0.5 percentage of participants |
p-value: 0.1495% CI: [0.26, 1.22]Regression, Cox
Secondary
Percentage of Participants With a Clinical Vertebral Fracture Through Month 24
A clinical vertebral fracture is a new or worsening vertebral fracture assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms of back pain indicative of a fracture, regardless of trauma severity or whether it is pathologic.
Time frame: 24 months
Population: All randomized participants; Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Clinical Vertebral Fracture Through Month 24 | 2.1 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Clinical Vertebral Fracture Through Month 24 | 0.9 percentage of participants |
p-value: <0.00195% CI: [0.24, 0.71]Regression, Cox
Secondary
Percentage of Participants With a Hip Fracture at the Primary Analysis
Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Time frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Hip Fracture at the Primary Analysis | 3.2 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Hip Fracture at the Primary Analysis | 2.0 percentage of participants |
p-value: 0.01595% CI: [0.42, 0.92]Regression, Cox
Secondary
Percentage of Participants With a Hip Fracture Through Month 12
Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Time frame: 12 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Hip Fracture Through Month 12 | 1.1 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Hip Fracture Through Month 12 | 0.7 percentage of participants |
p-value: 0.1995% CI: [0.33, 1.26]Regression, Cox
Secondary
Percentage of Participants With a Hip Fracture Through Month 24
Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Time frame: 24 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Hip Fracture Through Month 24 | 2.1 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Hip Fracture Through Month 24 | 1.5 percentage of participants |
p-value: 0.1795% CI: [0.46, 1.15]Regression, Cox
Secondary
Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis
Major nonvertebral fractures included a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.
Time frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis | 9.6 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis | 7.1 percentage of participants |
p-value: 0.00495% CI: [0.59, 0.9]Regression, Cox
Secondary
Percentage of Participants With a Major Osteoporotic Fracture Through Month 12
Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: 12 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Major Osteoporotic Fracture Through Month 12 | 4.2 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Major Osteoporotic Fracture Through Month 12 | 3.0 percentage of participants |
p-value: 0.05395% CI: [0.52, 1.01]Regression, Cox
Secondary
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4 according to the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader using the Semiquantitative method.
Time frame: 24 months
Population: Randomized participants with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture, including participants who had vertebrae with missing Genant semiquantitative scores at baseline whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24 | 9.2 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24 | 4.8 percentage of participants |
p-value: <0.00195% CI: [0.37, 0.64]Regression, Logistic
Comparison: The risk ratio (ratio of percentages, Romosozumab:Alendronate) was based on the Mantel Haenszel method, adjusted for age strata (\<75 vs. ≥75 years), the presence or absence of severe vertebral fracture at baseline, and baseline bone mineral density T-score at the total hip (≤ -2.5, \> -2.5).~Values \< 1 for risk ratio favor romosozumab.95% CI: [0.4, 0.66]
Comparison: The absolute risk reduction (difference in percentages, Alendronate - Romosozumab) was based on the Mantel-Haenszel method adjusted for age strata, baseline total hip BMD T-score (≤ -2.5, \> -2.5), and presence of severe vertebral fracture at baseline.~Positive values for absolute risk reduction favor romosozumab.95% CI: [2.8, 6.08]
Secondary
Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis
A nonvertebral fracture was defined as a documented fracture excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis | 10.6 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis | 8.7 percentage of participants |
p-value: 0.0495% CI: [0.66, 0.99]Regression, Cox
Secondary
Percentage of Participants With a Nonvertebral Fracture Through Month 12
A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: 12 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Nonvertebral Fracture Through Month 12 | 4.6 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Nonvertebral Fracture Through Month 12 | 3.4 percentage of participants |
p-value: 0.05795% CI: [0.54, 1.01]Regression, Cox
Secondary
Percentage of Participants With a Nonvertebral Fracture Through Month 24
A nonvertebral fracture was defined as a documented fracture excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Time frame: 24 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With a Nonvertebral Fracture Through Month 24 | 7.8 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With a Nonvertebral Fracture Through Month 24 | 6.3 percentage of participants |
p-value: 0.07495% CI: [0.64, 1.02]Regression, Cox
Secondary
Percentage of Participants With Any Fracture at the Primary Analysis
All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures.
Time frame: The primary analysis was performed when clinical fracture events had been confirmed in at least 330 patients and all participants had completed the month 24 visit. The median follow-up was 2.7 years (interquartile range, 2.2 to 3.3).
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With Any Fracture at the Primary Analysis | 19.1 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With Any Fracture at the Primary Analysis | 13.0 percentage of participants |
p-value: <0.00195% CI: [0.56, 0.76]Regression, Cox
Secondary
Percentage of Participants With Any Fracture Through Month 12
All fractures include any osteoporotic nonvertebral fractures that are not associated with high trauma severity or pathologic fractures and new or worsening vertebral fractures regardless of trauma severity or pathologic fractures.
Time frame: 12 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With Any Fracture Through Month 12 | 9.2 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With Any Fracture Through Month 12 | 6.5 percentage of participants |
p-value: 0.00295% CI: [0.57, 0.88]Regression, Cox
Secondary
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4 according to the Genant Semiquantitative Scoring method. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit. Incident vertebral fractures were confirmed by a second independent reader.
Time frame: 24 months
Population: Randomized participants with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture, including participants who had vertebrae with missing Genant semiquantitative scores at baseline whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24 | 2.5 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24 | 1.3 percentage of participants |
p-value: 0.00895% CI: [0.31, 0.85]Regression, Logistic
Comparison: The risk ratio (ratio of percentages, Romosozumab:Alendronate) was based on the Mantel Haenszel method, adjusted for age strata (\<75 vs. ≥75 years), the presence or absence of severe vertebral fracture at baseline, and baseline bone mineral density T-score at the total hip (≤ -2.5, \> -2.5).~Values \< 1 for risk ratio favor romosozumab.95% CI: [0.32, 0.85]
Comparison: The absolute risk reduction (difference in percentages, Alendronate - Romosozumab) was based on the Mantel-Haenszel method adjusted for age strata, baseline total hip BMD T-score (≤ -2.5, \> -2.5), and presence of severe vertebral fracture at baseline.~Positive values for absolute risk reduction favor romosozumab.95% CI: [0.33, 2.1]
Secondary
Percentage of Participants With New Vertebral Fractures Through Month 12
New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant Semiquantitative Scoring method based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height. Incident vertebral fractures were confirmed by a second independent reader.
Time frame: 12 months
Population: Randomized participants with a baseline and ≥ 1 postbaseline evaluation of vertebral fracture, including participants who had vertebrae with missing Genant semiquantitative scores at baseline whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alendronate/Alendronate | Percentage of Participants With New Vertebral Fractures Through Month 12 | 5.0 percentage of participants |
| Romosozumab/Alendronate | Percentage of Participants With New Vertebral Fractures Through Month 12 | 3.2 percentage of participants |
p-value: 0.00895% CI: [0.44, 0.89]Regression, Logistic
Comparison: The risk ratio (ratio of percentages, Romosozumab:Alendronate) was based on the Mantel Haenszel method, adjusted for age strata (\<75 vs. ≥75 years), the presence or absence of severe vertebral fracture at baseline, and baseline bone mineral density T-score at the total hip (≤ -2.5, \> -2.5).~Values \< 1 for risk ratio favor romosozumab.95% CI: [0.46, 0.89]
Comparison: The absolute risk reduction (difference in percentages, Alendronate - Romosozumab) was based on the Mantel-Haenszel method adjusted for age strata, baseline total hip BMD T-score (≤ -2.5, \> -2.5), and presence of severe vertebral fracture at baseline.~Positive values for absolute risk reduction favor romosozumab.95% CI: [0.51, 3.17]
Secondary
Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation at or before month 12; Last observation carried forward imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12 | 1.7 percent change | Standard Error 0.1 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12 | 4.9 percent change | Standard Error 0.1 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [2.9, 3.54]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation at or before month 12; Last observation carried forward imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12 | 5.0 percent change | Standard Error 0.1 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12 | 13.7 percent change | Standard Error 0.2 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [8.31, 9.09]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 24
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 24; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24 | 7.2 percent change | Standard Error 0.2 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24 | 15.3 percent change | Standard Error 0.2 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an analysis of covariance (ANCOVA) model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [7.58, 8.57]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation at or before month 12; Last observation carried forward imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12 | 2.8 percent change | Standard Error 0.1 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12 | 6.2 percent change | Standard Error 0.1 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [3.03, 3.6]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 24
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 24; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24 | 2.3 percent change | Standard Error 0.2 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24 | 6.0 percent change | Standard Error 0.2 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [3.4, 4.14]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 36
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 36; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36 | 2.4 percent change | Standard Error 0.2 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36 | 6.0 percent change | Standard Error 0.2 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [3.18, 3.97]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 36
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 36; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36 | 7.8 percent change | Standard Error 0.2 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36 | 15.2 percent change | Standard Error 0.2 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [6.84, 7.89]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 24
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 24; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24 | 3.5 percent change | Standard Error 0.1 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24 | 7.2 percent change | Standard Error 0.1 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [3.42, 4.1]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 36
Population: All randomized participants with a baseline and ≥ 1 post-baseline evaluation during the open-label period at or before month 36; Missing values were imputed by carrying forward the last non-missing post-baseline value in the open-label treatment period prior to the missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36 | 3.5 percent change | Standard Error 0.1 |
| Romosozumab/Alendronate | Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36 | 7.2 percent change | Standard Error 0.1 |
Comparison: Between-group comparisons of the percent change from baseline in bone mineral density were analyzed using an ANCOVA model adjusted for treatment, age strata, presence of severe vertebral fracture at baseline, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction.p-value: <0.00195% CI: [3.29, 4.02]ANCOVA