Trial Outcomes & Findings for Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis (NCT NCT01631214)

Last Updated: 2025-02-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4093 participants

Primary outcome timeframe

24 months

Results posted on

2025-02-21

Participant Flow

The study was conducted at 270 centers in 41 countries globally from 04 May 2012 to 29 June 2017.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	2047	2046
Overall Study Received Double-blind Treatment	2040	2038
Overall Study Completed Double-blind Period	1823	1831
Overall Study Completed Primary Analysis Period	1576	1574
Overall Study COMPLETED	1503	1523
Overall Study NOT COMPLETED	544	523

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	276	290
Overall Study Death	113	106
Overall Study Lost to Follow-up	54	40
Overall Study Adverse Event	45	45
Overall Study Other	22	19
Overall Study Noncompliance	16	15
Overall Study Requirement for Alternative Therapy	8	3
Overall Study Protocol Deviation	4	3
Overall Study Ineligibility determined	5	2
Overall Study Administrative Decision	1	0

Baseline Characteristics

Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.	Total n=4093 Participants Total of all reporting groups
Age, Continuous	74.2 years STANDARD_DEVIATION 7.5 • n=5 Participants	74.4 years STANDARD_DEVIATION 7.5 • n=7 Participants	74.3 years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	2047 Participants n=5 Participants	2046 Participants n=7 Participants	4093 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	662 Participants n=5 Participants	631 Participants n=7 Participants	1293 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1385 Participants n=5 Participants	1415 Participants n=7 Participants	2800 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	149 Participants n=5 Participants	137 Participants n=7 Participants	286 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	23 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	1415 Participants n=5 Participants	1447 Participants n=7 Participants	2862 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	446 Participants n=5 Participants	436 Participants n=7 Participants	882 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age Strata per Randomization < 75 years	976 Participants n=5 Participants	973 Participants n=7 Participants	1949 Participants n=5 Participants
Age Strata per Randomization ≥ 75 years	1071 Participants n=5 Participants	1073 Participants n=7 Participants	2144 Participants n=5 Participants
Severe Vertebral Fracture Presence	1321 Participants n=5 Participants	1369 Participants n=7 Participants	2690 Participants n=5 Participants
Severe Vertebral Fracture Absence	726 Participants n=5 Participants	677 Participants n=7 Participants	1403 Participants n=5 Participants
Total Hip Bone Mineral Density (BMD) T-score ≤ -2.5	1384 Participants n=5 Participants	1356 Participants n=7 Participants	2740 Participants n=5 Participants
Total Hip Bone Mineral Density (BMD) T-score > -2.5	662 Participants n=5 Participants	690 Participants n=7 Participants	1352 Participants n=5 Participants
Total Hip Bone Mineral Density (BMD) T-score Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1834 Participants 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.	Romosozumab/Alendronate n=1825 Participants 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.
Percentage of Participants With New Vertebral Fractures Through Month 24	8.0 percentage of participants	4.1 percentage of participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Clinical Fracture at the Primary Analysis	13.0 percentage of participants	9.7 percentage of participants

SECONDARY outcome

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Nonvertebral Fracture at the Primary Analysis	10.6 percentage of participants	8.7 percentage of participants

SECONDARY outcome

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With Any Fracture at the Primary Analysis	19.1 percentage of participants	13.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1834 Participants 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.	Romosozumab/Alendronate n=1825 Participants 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.
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24	9.2 percentage of participants	4.8 percentage of participants

SECONDARY outcome

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Major Nonvertebral Fracture at the Primary Analysis	9.6 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Population: All randomized participants

Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Hip Fracture at the Primary Analysis	3.2 percentage of participants	2.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1834 Participants 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.	Romosozumab/Alendronate n=1825 Participants 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.
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24	2.5 percentage of participants	1.3 percentage of participants

SECONDARY outcome

Timeframe: 24 months

Population: All randomized participants; Missing values for clinical fractures were imputed using last observation carried forward.

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Clinical Fracture Through Month 24	9.6 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Timeframe: 24 months

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Nonvertebral Fracture Through Month 24	7.8 percentage of participants	6.3 percentage of participants

SECONDARY outcome

Timeframe: 24 months

Population: All randomized participants

Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Hip Fracture Through Month 24	2.1 percentage of participants	1.5 percentage of participants

SECONDARY outcome

Timeframe: 24 months

Population: All randomized participants; Last observation carried forward imputation was used.

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Clinical Vertebral Fracture Through Month 24	2.1 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants; Missing values for clinical fractures were imputed using last observation carried forward.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Clinical Fracture Through Month 12	5.4 percentage of participants	3.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1703 Participants 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.	Romosozumab/Alendronate n=1696 Participants 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.
Percentage of Participants With New Vertebral Fractures Through Month 12	5.0 percentage of participants	3.2 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With Any Fracture Through Month 12	9.2 percentage of participants	6.5 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Nonvertebral Fracture Through Month 12	4.6 percentage of participants	3.4 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants

Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Hip Fracture Through Month 12	1.1 percentage of participants	0.7 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Major Osteoporotic Fracture Through Month 12	4.2 percentage of participants	3.0 percentage of participants

SECONDARY outcome

Timeframe: 12 months

Population: All randomized participants; Last observation carried forward imputation was used.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=2047 Participants 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.	Romosozumab/Alendronate n=2046 Participants 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.
Percentage of Participants With a Clinical Vertebral Fracture Through Month 12	0.9 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1577 Participants 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.	Romosozumab/Alendronate n=1571 Participants 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.
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 24	7.2 percent change Standard Error 0.2	15.3 percent change Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1627 Participants 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.	Romosozumab/Alendronate n=1622 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24	3.5 percent change Standard Error 0.1	7.2 percent change Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1627 Participants 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.	Romosozumab/Alendronate n=1622 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at at Month 24	2.3 percent change Standard Error 0.2	6.0 percent change Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1718 Participants 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.	Romosozumab/Alendronate n=1722 Participants 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.
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12	5.0 percent change Standard Error 0.1	13.7 percent change Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1781 Participants 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.	Romosozumab/Alendronate n=1781 Participants 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.
Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12	2.8 percent change Standard Error 0.1	6.2 percent change Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1781 Participants 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.	Romosozumab/Alendronate n=1781 Participants 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.
Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12	1.7 percent change Standard Error 0.1	4.9 percent change Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1597 Participants 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.	Romosozumab/Alendronate n=1593 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Lumbar Spine at Month 36	7.8 percent change Standard Error 0.2	15.2 percent change Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1653 Participants 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.	Romosozumab/Alendronate n=1653 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 36	3.5 percent change Standard Error 0.1	7.2 percent change Standard Error 0.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alendronate/Alendronate n=1653 Participants 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.	Romosozumab/Alendronate n=1653 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 36	2.4 percent change Standard Error 0.2	6.0 percent change Standard Error 0.2

Adverse Events

Double-blind Period: Alendronate 70 mg QW

Serious events: 278 serious events

Other events: 1190 other events

Deaths: 22 deaths

Double-blind Period: Romosozumab 210 mg QM

Serious events: 262 serious events

Other events: 1112 other events

Deaths: 30 deaths

Overall Study: Alendronate / Alendronate

Serious events: 638 serious events

Other events: 1498 other events

Deaths: 103 deaths

Overall Study: Romosozumab / Alendronate

Serious events: 611 serious events

Other events: 1424 other events

Deaths: 101 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER