Low Bone Mineral Density, Postmenopausal Osteoporosis
Conditions
Brief summary
The primary objective was to determine the effect of treatment with romosozumab versus placebo at month 12 on the percent change from baseline in bone mineral density (BMD) at the lumbar spine in postmenopausal women with low bone density.
Detailed description
This study included a 24-month treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention. * 24-month Romosozumab Treatment Phase (months 1 to 24): Participants were randomized in a 1:1:1:1:1:1:1:1 ratio to receive 1 of 5 double-blind dosing regimens of romosozumab or placebo or open-label alendronate (ALN) or open-label teriparatide (TPTD) for the first 12 months of the study. At month 12, participants in the romosozumab and placebo groups continued their assigned treatment for an additional 12 months, participants in the TPTD group ended study participation, and participants in the ALN group transitioned to receive romosozumab 140 mg subcutaneously (SC) every month (QM) for an additional 12 months (months 12 to 24). * 12-month Denosumab Extension Phase (months 24 to 36): At the end of the 24-month romosozumab treatment phase, eligible participants were randomized 1:1 within their original treatment group to receive either denosumab or placebo every 6 months (Q6M) for 12 months. * 12-month Romosozumab Retreatment Phase (months 36 to 48): From months 36 to 48, participants initially randomized to romosozumab or placebo received romosozumab 210 mg SC QM. Participants who initially received ALN ended their participation at month 36 and were not retreated with romosozumab. * 24-month Follow-on Phase (months 48 to 72): At month 48, participants received 1 dose of zoledronic acid 5 mg intravenously or no intervention for an additional 24 months.
Interventions
Administered by subcutaneous injection QM or Q3M.
DRUGAlendronate
Administered orally once a week
DRUGTeriparatide
Teriparatide 20 μg administered by subcutaneous injection once a day
DRUGRomosozumab
Administered by subcutaneous injection
DRUGDenosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Administered by subcutaneous injection Q6M
DRUGZoledronic acid
Zoledronic acid 5 mg administered intravenously
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 women, aged ≥ 55 to ≤ 85 * Low BMD measured by dual energy X-ray absorptiometry (DXA) and assessed by the central imaging vendor (equivalent to T-scores between -2.0 and -3.5)
Exclusion criteria
* History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50 * Untreated hyper- or hypothyroidism * Current hyper- or hypoparathyroidism, hypo- or hypercalcemia * Elevated transaminases * Significantly impaired renal function * Positive for: human immunodeficiency virus (HIV), hepatitis-C or hepatitis-B surface antigen * Malignancy * History of solid organ or bone marrow transplants * Use of agents affecting bone metabolism * Contraindicated or intolerant of alendronate therapy * Contraindicated or intolerant of teriparatide therapy Inclusion Criteria for the 12 month extension phase (Month 24 to 36): \- Normocalcemia at or after the Month 21 visit but before the Month 24 study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | Baseline to 12 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at Month 6 in BMD of the Total Hip | Baseline to 6 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables. |
| Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | Baseline to 6 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables. |
| Percent Change From Baseline at Month 12 in BMD of the Total Hip | Baseline to 12 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables. |
| Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | Baseline to 12 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables. |
| Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | Baseline to 6 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables. |
| Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Baseline and months 1, 3, 6, 9, and 12 | Percent change from baseline in the bone turnover marker (BTM) P1NP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. |
| Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Baseline and months 1, 3, 6, 9, and 12 | Percent change from baseline in the bone turnover marker (BTM) CTX was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. |
| Percent Change From Baseline in Osteocalcin | Baseline and months 1, 3, 6, 9, and 12 | Percent change from baseline in the bone turnover marker (BTM) osteocalcin was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. |
| Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Baseline and months 1, 3, 6, 9, and 12 | Percent change from baseline in the bone turnover marker (BTM) BSAP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. |
| Percent Change From Baseline at Month 12 in BMD of the Distal Radius | Baseline to 12 months | Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline in distal radius BMD was analyzed using an analysis of covariance (ANCOVA) model with the percent change from baseline to Month 12 in DXA BMD as dependent variable, baseline BMD value, machine type, interaction of baseline BMD and machine type, treatment (categorical) and geographic region as the independent class variables. |
Participant flow
Recruitment details
This study was conducted at 29 centers in 7 countries in Europe, North America, and Argentina. Participants were enrolled from the 3rd of June 2009 to the 17th of February 2010.
Pre-assignment details
A total of 807 patients were screened and 419 were randomized. The study included a 24-month treatment phase, followed by rerandomization to a 12-month extension phase with denosumab or placebo; followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching to romosozumab once a month (QM) or once every 3 months (Q3M) administered subcutaneously for 24 months. | 52 |
| Alendronate Participants received open-label alendronate (ALN) 70 mg orally (PO) every week (QW) for 12 months. At month 12 participants transitioned to receive romosozumab 140 mg subcutaneously every month for an additional 12 months (months 12 to 24). | 51 |
| Teriparatide Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation. | 55 |
| Romosozumab 70 mg QM Participants received double-blind romosozumab 70 mg subcutaneously every month for 24 months. | 51 |
| Romosozumab 140 mg Q3M Participants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months. | 54 |
| Romosozumab 140 mg QM Participants received double-blind romosozumab 140 mg QM subcutaneously for 24 months. | 51 |
| Romosozumab 210 mg Q3M Participants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months. | 53 |
| Romosozumab 210 mg QM Participants received double-blind romosozumab 210 mg QM subcutaneously for 24 months. | 52 |
| Total | 419 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Months 1-24: Romosozumab Treatment Phase | Administrative Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Adverse Event | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Death | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Lost to Follow-up | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Noncompliance | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | On-study But No Month 24 Visit | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Other | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Protocol Deviation | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 1-24: Romosozumab Treatment Phase | Withdrawal by Subject | 4 | 3 | 4 | 6 | 5 | 6 | 4 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 24-36: Denosumab Extension Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 24-36: Denosumab Extension Phase | Noncompliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 24-36: Denosumab Extension Phase | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 24-36: Denosumab Extension Phase | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 24-36: Denosumab Extension Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 36-48: Romosozumab Retreatment | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 36-48: Romosozumab Retreatment | Continuing the re-treatment phase | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 36-48: Romosozumab Retreatment | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Months 36-48: Romosozumab Retreatment | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Months 36-48: Romosozumab Retreatment | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| Months 48-72: Follow-on Phase | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Months 48-72: Follow-on Phase | Ineligibility Determined | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Months 48-72: Follow-on Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Alendronate | Teriparatide | Romosozumab 70 mg QM | Romosozumab 140 mg Q3M | Romosozumab 140 mg QM | Romosozumab 210 mg Q3M | Romosozumab 210 mg QM | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 6.5 | 67.1 years STANDARD_DEVIATION 5.8 | 66.8 years STANDARD_DEVIATION 5.7 | 65.8 years STANDARD_DEVIATION 6.1 | 67.3 years STANDARD_DEVIATION 6.7 | 67.8 years STANDARD_DEVIATION 6.2 | 66.1 years STANDARD_DEVIATION 7.3 | 66.3 years STANDARD_DEVIATION 6.5 | 66.8 years STANDARD_DEVIATION 6.4 |
| Age, Customized < 65 years | 20 Participants | 18 Participants | 21 Participants | 21 Participants | 20 Participants | 12 Participants | 24 Participants | 18 Participants | 154 Participants |
| Age, Customized ≥ 65 years | 32 Participants | 33 Participants | 34 Participants | 30 Participants | 34 Participants | 39 Participants | 29 Participants | 34 Participants | 265 Participants |
| Bone-specific Alkaline Phosphatase (BSAP) | 11.79 μg/L | 12.93 μg/L | 13.34 μg/L | 11.82 μg/L | 13.19 μg/L | 11.78 μg/L | 12.61 μg/L | 12.37 μg/L | 12.44 μg/L |
| Distal 1/3 Radius BMD T-score | -1.85 T-score STANDARD_DEVIATION 1.04 | -2.08 T-score STANDARD_DEVIATION 0.99 | -2.05 T-score STANDARD_DEVIATION 1.21 | -1.78 T-score STANDARD_DEVIATION 1.14 | -2.24 T-score STANDARD_DEVIATION 1.06 | -2.11 T-score STANDARD_DEVIATION 1.12 | -1.98 T-score STANDARD_DEVIATION 1.04 | -2.03 T-score STANDARD_DEVIATION 0.99 | -2.01 T-score STANDARD_DEVIATION 1.08 |
| Femoral Neck BMD T-score | -1.76 T-score STANDARD_DEVIATION 0.56 | -1.91 T-score STANDARD_DEVIATION 0.61 | -1.79 T-score STANDARD_DEVIATION 0.67 | -2.06 T-score STANDARD_DEVIATION 0.55 | -2.00 T-score STANDARD_DEVIATION 0.54 | -2.03 T-score STANDARD_DEVIATION 0.58 | -2.02 T-score STANDARD_DEVIATION 0.57 | -1.87 T-score STANDARD_DEVIATION 0.58 | -1.93 T-score STANDARD_DEVIATION 0.59 |
| Lumbar Spine Bone Mineral Density (BMD) T-score | -2.29 T-score STANDARD_DEVIATION 0.66 | -2.08 T-score STANDARD_DEVIATION 0.69 | -2.29 T-score STANDARD_DEVIATION 0.57 | -2.35 T-score STANDARD_DEVIATION 0.79 | -2.44 T-score STANDARD_DEVIATION 0.7 | -2.27 T-score STANDARD_DEVIATION 0.77 | -2.21 T-score STANDARD_DEVIATION 0.69 | -2.33 T-score STANDARD_DEVIATION 0.57 | -2.29 T-score STANDARD_DEVIATION 0.68 |
| Osteocalcin | 17.95 ng/mL | 19.37 ng/mL | 19.47 ng/mL | 19.03 ng/mL | 19.93 ng/mL | 18.56 ng/mL | 17.72 ng/mL | 18.36 ng/mL | 18.84 ng/mL |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants | 5 Participants | 8 Participants | 3 Participants | 8 Participants | 6 Participants | 48 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 47 Participants | 46 Participants | 44 Participants | 46 Participants | 43 Participants | 48 Participants | 44 Participants | 44 Participants | 362 Participants |
| Serum Procollagen Type 1 N-telopeptide (P1NP) | 47.76 μg/L | 49.25 μg/L | 48.78 μg/L | 50.36 μg/L | 48.63 μg/L | 48.13 μg/L | 49.24 μg/L | 52.58 μg/L | 49.37 μg/L |
| Serum Type 1 Collagen C-telopeptide (CTX) | 481.0 ng/L | 494.0 ng/L | 505.5 ng/L | 486.0 ng/L | 525.0 ng/L | 532.0 ng/L | 478.0 ng/L | 519.0 ng/L | 501.5 ng/L |
| Sex: Female, Male Female | 52 Participants | 51 Participants | 55 Participants | 51 Participants | 54 Participants | 51 Participants | 53 Participants | 52 Participants | 419 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Hip BMD T-score | -1.35 T-score STANDARD_DEVIATION 0.67 | -1.55 T-score STANDARD_DEVIATION 0.68 | -1.32 T-score STANDARD_DEVIATION 0.78 | -1.69 T-score STANDARD_DEVIATION 0.67 | -1.58 T-score STANDARD_DEVIATION 0.51 | -1.67 T-score STANDARD_DEVIATION 0.65 | -1.65 T-score STANDARD_DEVIATION 0.63 | -1.45 T-score STANDARD_DEVIATION 0.65 | -1.53 T-score STANDARD_DEVIATION 0.66 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 30 | 19 / 20 | 38 / 51 | 36 / 54 | 46 / 50 | 40 / 52 | 41 / 49 | 45 / 53 | 40 / 51 | 28 / 30 | 20 / 20 | 49 / 51 | 48 / 50 | 47 / 52 | 46 / 49 | 51 / 53 | 47 / 51 | 15 / 18 | 15 / 17 | 12 / 19 | 15 / 19 | 57 / 90 | 59 / 89 | 12 / 12 | 11 / 15 | 53 / 72 | 55 / 68 | 34 / 51 | 1 / 3 | 10 / 11 | 8 / 12 | 44 / 56 | 7 / 8 |
| serious Total, serious adverse events | 3 / 30 | 4 / 20 | 4 / 51 | 5 / 54 | 5 / 50 | 3 / 52 | 2 / 49 | 3 / 53 | 6 / 51 | 5 / 30 | 4 / 20 | 8 / 51 | 9 / 50 | 8 / 52 | 8 / 49 | 6 / 53 | 7 / 51 | 2 / 18 | 1 / 17 | 2 / 19 | 0 / 19 | 3 / 90 | 8 / 89 | 0 / 12 | 1 / 15 | 4 / 72 | 3 / 68 | 8 / 51 | 0 / 3 | 1 / 11 | 1 / 12 | 9 / 56 | 1 / 8 |
Outcome results
Primary
Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.
Time frame: Baseline to 12 months
Population: All randomized participants who had non-missing baseline and month 12 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | -0.1 percent change |
| Alendronate | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 4.1 percent change |
| Teriparatide | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 7.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 5.4 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 5.4 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 9.1 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 5.5 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 11.3 percent change |
| Romosozumab Monthly | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 8.6 percent change |
| Romosozumab Every 3 Months | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 5.5 percent change |
| Romosozumab 140 mg | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 7.3 percent change |
| Romosozumab 210 mg | Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine | 8.4 percent change |
Comparison: A linear mixed effects model was fit with the percent change from baseline to months 3, 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, geographic region (Latin America, North America, Europe), visit, treatment regimen (categorical), interaction of treatment regimen and visit as the independent variables.p-value: <0.000195% CI: [7.5, 9.9]Linear Mixed Effects Model
Comparison: A linear mixed effects model was fit with the percent change from baseline to months 3, 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, geographic region (Latin America, North America, Europe), visit, treatment regimen (categorical), interaction of treatment regimen and visit as the independent variables.p-value: <0.000195% CI: [4.3, 6.9]Linear Mixed Effects Model
Comparison: A linear mixed effects model was fit with the percent change from baseline to months 3, 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, geographic region (Latin America, North America, Europe), visit, treatment regimen (categorical), interaction of treatment regimen and visit as the independent variables.p-value: <0.000195% CI: [6.1, 8.7]Linear Mixed Effects Model
Comparison: A linear mixed effects model was fit with the percent change from baseline to months 3, 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, geographic region (Latin America, North America, Europe), visit, treatment regimen (categorical), interaction of treatment regimen and visit as the independent variables.p-value: <0.000195% CI: [7.3, 9.8]Linear Mixed Effects Model
Secondary
Percent Change From Baseline at Month 12 in BMD of the Distal Radius
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline in distal radius BMD was analyzed using an analysis of covariance (ANCOVA) model with the percent change from baseline to Month 12 in DXA BMD as dependent variable, baseline BMD value, machine type, interaction of baseline BMD and machine type, treatment (categorical) and geographic region as the independent class variables.
Time frame: Baseline to 12 months
Population: All randomized participants who had non-missing baseline and month 12 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -0.9 percent change |
| Alendronate | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -0.3 percent change |
| Teriparatide | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -1.7 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -1.8 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -1.1 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -1.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -0.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 12 in BMD of the Distal Radius | -1.2 percent change |
Secondary
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Time frame: Baseline to 12 months
Population: All randomized participants who had non-missing baseline and month 12 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | -1.1 percent change |
| Alendronate | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 1.2 percent change |
| Teriparatide | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 1.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 0.6 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 1.8 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 4.2 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 1.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 12 in BMD of the Femoral Neck | 3.7 percent change |
Secondary
Percent Change From Baseline at Month 12 in BMD of the Total Hip
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Time frame: Baseline to 12 months
Population: All randomized participants who had non-missing baseline and month 12 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 12 in BMD of the Total Hip | -0.7 percent change |
| Alendronate | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 1.9 percent change |
| Teriparatide | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 1.3 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 1.3 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 1.3 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 3.4 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 1.9 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 12 in BMD of the Total Hip | 4.1 percent change |
Secondary
Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Time frame: Baseline to 6 months
Population: All randomized participants who had non-missing baseline and month 6 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 0.3 percent change |
| Alendronate | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 2.6 percent change |
| Teriparatide | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 4.8 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 4.1 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 4.2 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 7.1 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 4.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine | 8.2 percent change |
Secondary
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Time frame: Baseline to 6 months
Population: All randomized participants who had non-missing baseline and month 6 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | -0.4 percent change |
| Alendronate | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 0.5 percent change |
| Teriparatide | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 0.5 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 0.2 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 0.4 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 2.1 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 0.9 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 6 in BMD of the Femoral Neck | 1.9 percent change |
Secondary
Percent Change From Baseline at Month 6 in BMD of the Total Hip
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Time frame: Baseline to 6 months
Population: All randomized participants who had non-missing baseline and month 6 measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline at Month 6 in BMD of the Total Hip | -0.6 percent change |
| Alendronate | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 0.9 percent change |
| Teriparatide | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 0.5 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 0.5 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 0.9 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 2.2 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 1.1 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline at Month 6 in BMD of the Total Hip | 2.9 percent change |
Secondary
Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
Percent change from baseline in the bone turnover marker (BTM) BSAP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Time frame: Baseline and months 1, 3, 6, 9, and 12
Population: All randomized participants with baseline and at least one post baseline measurement on or prior to the month 12 visit and with available data at each time point. Data were not collected for participants in the alendronate and teriparatide groups at month 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | -7.6 percent change |
| Placebo | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | 3.5 percent change |
| Placebo | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | 9.2 percent change |
| Placebo | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | -1.1 percent change |
| Placebo | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -4.1 percent change |
| Alendronate | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | -32.5 percent change |
| Alendronate | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | -30.5 percent change |
| Alendronate | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | -31.2 percent change |
| Alendronate | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -35.4 percent change |
| Teriparatide | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | 21.8 percent change |
| Teriparatide | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | 45.7 percent change |
| Teriparatide | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | 41.8 percent change |
| Teriparatide | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | 29.8 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | -4.9 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | 11.7 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | -8.5 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -8.7 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | -2.6 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -18.2 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | -10.8 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | -12.5 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | -18.0 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | 35.1 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -6.6 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | 29.3 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | 1.3 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | -5.5 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | -5.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | -17.7 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | -20.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | -17.3 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | 47.5 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | -12.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 1 | 60.9 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 9 | 10.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 6 | 13.1 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 3 | 27.4 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP) | Month 12 | 9.2 percent change |
Secondary
Percent Change From Baseline in Osteocalcin
Percent change from baseline in the bone turnover marker (BTM) osteocalcin was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Time frame: Baseline and months 1, 3, 6, 9, and 12
Population: All randomized participants with baseline and at least one post baseline measurement on or prior to the month 12 visit and with available data at each time point. Data were not collected for participants in the alendronate and teriparatide groups at month 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Osteocalcin | Month 3 | 4.1 percent change |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 9 | -6.0 percent change |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 12 | -14.1 percent change |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 1 | -1.6 percent change |
| Placebo | Percent Change From Baseline in Osteocalcin | Month 6 | -7.1 percent change |
| Alendronate | Percent Change From Baseline in Osteocalcin | Month 9 | -50.9 percent change |
| Alendronate | Percent Change From Baseline in Osteocalcin | Month 3 | -28.7 percent change |
| Alendronate | Percent Change From Baseline in Osteocalcin | Month 12 | -50.3 percent change |
| Alendronate | Percent Change From Baseline in Osteocalcin | Month 6 | -40.6 percent change |
| Teriparatide | Percent Change From Baseline in Osteocalcin | Month 3 | 104.7 percent change |
| Teriparatide | Percent Change From Baseline in Osteocalcin | Month 12 | 91.6 percent change |
| Teriparatide | Percent Change From Baseline in Osteocalcin | Month 9 | 99.9 percent change |
| Teriparatide | Percent Change From Baseline in Osteocalcin | Month 6 | 106.7 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Osteocalcin | Month 9 | -26.9 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Osteocalcin | Month 1 | 28.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Osteocalcin | Month 3 | -0.3 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Osteocalcin | Month 6 | -11.8 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Osteocalcin | Month 12 | -27.3 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 6 | -16.5 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 12 | -24.7 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 9 | -29.0 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 3 | -5.6 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 1 | 60.1 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Osteocalcin | Month 6 | -7.4 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Osteocalcin | Month 1 | 53.1 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Osteocalcin | Month 3 | 15.6 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Osteocalcin | Month 9 | -27.7 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Osteocalcin | Month 12 | -31.1 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 9 | -30.7 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 6 | -23.2 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 3 | -3.7 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 1 | 77.9 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Osteocalcin | Month 12 | -26.2 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Osteocalcin | Month 1 | 78.6 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Osteocalcin | Month 9 | -4.0 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Osteocalcin | Month 6 | 10.0 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Osteocalcin | Month 3 | 41.6 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Osteocalcin | Month 12 | -12.5 percent change |
Secondary
Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
Percent change from baseline in the bone turnover marker (BTM) P1NP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Time frame: Baseline and months 1, 3, 6, 9, and 12
Population: All randomized participants with baseline and at least one post baseline measurement on or prior to the month 12 visit and with available data at each time point. Data were not collected for participants in the alendronate and teriparatide groups at month 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -5.9 percent change |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | -0.7 percent change |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -8.7 percent change |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -5.4 percent change |
| Placebo | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -10.6 percent change |
| Alendronate | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -60.8 percent change |
| Alendronate | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -60.8 percent change |
| Alendronate | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -57.0 percent change |
| Alendronate | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -50.8 percent change |
| Teriparatide | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | 97.1 percent change |
| Teriparatide | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | 138.0 percent change |
| Teriparatide | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | 98.3 percent change |
| Teriparatide | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | 116.8 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 24.2 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -26.9 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -9.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -20.0 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -23.0 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -23.3 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 61.4 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -15.5 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -22.8 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -23.8 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -18.6 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | 3.8 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -31.2 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -26.1 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 55.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | -25.5 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -29.7 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -30.1 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 75.8 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | -19.5 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 1 | 92.2 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 12 | -17.2 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 6 | 6.9 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 3 | 25.6 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) | Month 9 | -5.8 percent change |
Secondary
Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
Percent change from baseline in the bone turnover marker (BTM) CTX was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Time frame: Baseline and months 1, 3, 6, 9, and 12
Population: All randomized participants with baseline and at least one post baseline measurement on or prior to the month 12 visit and with available data at each time point. Data were not collected for participants in the alendronate and teriparatide groups at month 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -2.4 percent change |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | 1.0 percent change |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | 9.8 percent change |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -3.9 percent change |
| Placebo | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | 2.7 percent change |
| Alendronate | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -64.4 percent change |
| Alendronate | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -65.0 percent change |
| Alendronate | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -66.7 percent change |
| Alendronate | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -64.2 percent change |
| Teriparatide | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | 69.4 percent change |
| Teriparatide | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | 77.0 percent change |
| Teriparatide | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | 81.3 percent change |
| Teriparatide | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | 93.5 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -15.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -22.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -21.5 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -18.1 percent change |
| Romosozumab 70 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -20.3 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -8.4 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | 12.2 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | 1.3 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -6.2 percent change |
| Romosozumab 140 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -19.2 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -24.6 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -35.4 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -26.5 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -27.7 percent change |
| Romosozumab 140 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -33.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -11.7 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -10.5 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -12.6 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -33.0 percent change |
| Romosozumab 210 mg Q3M | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -6.6 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 1 | -28.5 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 9 | -17.2 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 6 | -8.7 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 3 | -3.7 percent change |
| Romosozumab 210 mg QM | Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) | Month 12 | -22.5 percent change |