CompletedNCT00896532Updated Sep 22, 2022Results posted

Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density

A Phase 2 interventional study of Placebo to Romosozumab and Alendronate in Low Bone Mineral Density and Postmenopausal Osteoporosis, sponsored by Amgen. Completed. Open to female participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2022-09-22.

Sponsored by Amgen · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 419
Allocation: Randomized
Ages: 55 Years to 85 Years
Sex: Female

Study 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.

Read the 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.

Conditions studied

Low Bone Mineral Density
Postmenopausal Osteoporosis

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In context

Bone Diseases, Metabolic

487 studies on the registry are indexed under Bone Diseases, Metabolic; 74 are open to participants now.

This study's enrollment of 419 is above the median of 61 across 372 interventional studies indexed under Bone Diseases, Metabolic.

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Lead sponsor

Amgen is the lead sponsor of 1,044 studies on the registry; 51 are open to participants now.

Of its 246 completed or terminated interventional studies of FDA-regulated products, 164 (67%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 55 Years to 85 Years
Sexes eligible: Female
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Exclusion Criteria for the 12 month extension phase (Month 24 to 36)

Incidence of a clinical vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis during the initial 24 month treatment phase of the study
A BMD loss of ≥ 7.0% from baseline at any time up to the Month 18 visit of the initial 24-month treatment phase
Malignancy
History of osteonecrosis of the jaw
Use of proscribed medication during the initial 24 month treatment phase
Contraindicated or intolerant of denosumab therapy

Inclusion Criteria for the 12 month re-treatment phase (Month 36 to 48)

Albumin adjusted serum calcium of the most recent blood draw at or after the Month 30 visit but before the Month 36 study visit. Calcium repletion is permitted and central laboratory analysis of albumin adjusted serum calcium may be repeated before the Month 36 study visit
Participation in Group A or B during initial 24 month treatment phase
Subject has reached M36 of the study
Appropriate written informed consent must be obtained

Exclusion Criteria for the 12 month re-treatment phase (Month 36 to 48)

New malignancy
Use of proscribed medication during the 12 month extension phase

Inclusion Criteria for the 24 month follow-on phase (Month 48 to 72) General inclusion criteria for participation

Subject has reached month 48 of the study
Appropriate written informed consent must be obtained Inclusion criteria for assignment to the no intervention group
During the 24 month AMG 785 treatment phase, subject was assigned to any AMG 785 treatment group
During the 12 month denosumab extension phase, subject was assigned to the denosumab treatment group Exclusion for the 24 month follow-on phase (Month 48 to 72)
New malignancy
Use of proscribed meds during the 12 month re-treatment phase
Partial informed consent withdrawal and discontinuation of investigational product at any time up to month 48 visit
Incidence of a clinical vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis during the initial 24 month treatment phase of the study
BMD T-score of ≤ -2.5 at the lumbar spine, total hip, or femoral neck based on local read of the DXA scans at month 48
Intolerance to zoledronic acid

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 419 participants (actual)

Study arms

Placebo comparator
Placebo
Participants received placebo matching to romosozumab once a month (QM) or once every 3 months (Q3M) administered subcutaneously (SC) for up to 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Placebo to Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid
Active comparator
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). Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. At month 36 participants ended study participation.
Drug: Alendronate · Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab
Active comparator
Teriparatide
Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.
Drug: Teriparatide
Experimental
Romosozumab 70 mg QM
Participants received double-blind romosozumab 70 mg subcutaneously every month for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid
Experimental
Romosozumab 140 mg Q3M
Participants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid
Experimental
Romosozumab 140 mg QM
Participants received double-blind romosozumab 140 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid
Experimental
Romosozumab 210 mg Q3M
Participants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid
Experimental
Romosozumab 210 mg QM
Participants received double-blind romosozumab 210 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Drug: Romosozumab · Drug: Denosumab · Drug: Placebo to Denosumab · Drug: Zoledronic acid

Interventions

DrugPlacebo to Romosozumab
Administered by subcutaneous injection QM or Q3M.
DrugAlendronate
Administered orally once a week
Also known as: Fosamax
DrugTeriparatide
Teriparatide 20 μg administered by subcutaneous injection once a day
Also known as: Forsteo
DrugRomosozumab
Administered by subcutaneous injection
Also known as: AMG 785, EVENITY™
DrugDenosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Also known as: Prolia®
DrugPlacebo to Denosumab
Administered by subcutaneous injection Q6M
DrugZoledronic acid
Zoledronic acid 5 mg administered intravenously
Also known as: Aclasta

What researchers measure

Primary outcomes

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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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

Results

Posted Dec 14, 2018

Participant flow

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.

Months 1-24: Romosozumab Treatment Phase

Participant flow — Months 1-24: Romosozumab Treatment Phase
Milestone	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Started	52	51	55	51	54	51	53	52
Received treatment	51	51	54	49	53	48	53	51
Completed 12 months	47	49	46	45	50	46	51	49
Completed	46	45	46	39	46	43	48	48
Not completed	6	6	9	12	8	8	5	4
Withdrew: Protocol deviation	0	0	0	1	0	1	0	0
Withdrew: Adverse event	1	2	1	2	1	1	1	0
Withdrew: Withdrawal by subject	4	3	4	6	5	6	4	4
Withdrew: Lost to follow-up	0	0	2	0	1	0	0	0
Withdrew: Death	1	0	0	1	0	0	0	0
Withdrew: Administrative decision	0	0	1	0	0	0	0	0
Withdrew: Noncompliance	0	0	1	0	0	0	0	0
Withdrew: On-study but no month 24 visit	0	0	0	1	0	0	0	0
Withdrew: Other	0	1	0	1	1	0	0	0

Months 24-36: Denosumab Extension Phase

Participant flow — Months 24-36: Denosumab Extension Phase
Milestone	Month 24-36: Placebo/Placebo	Month 24-36: Placebo/Denosumab	Month 24-36: Alendronate/Romosozumab/Placebo	Month 24-36: Alendronate/Romosozumab/Denosumab	Month 24-36: Romosozumab/Placebo	Month 24-36: Romosozumab/Denosumab
Started	18	18	20	21	93	90
Received treatment	18	18	19	19	90	88
Completed	17	18	18	19	88	88
Not completed	1	0	2	2	5	2
Withdrew: Protocol deviation	1	0	0	0	0	0
Withdrew: Noncompliance	0	0	0	0	1	0
Withdrew: Adverse event	0	0	1	0	1	0
Withdrew: Withdrawal by subject	0	0	0	0	1	1
Withdrew: Other	0	0	1	2	2	1

Months 36-48: Romosozumab Retreatment

Participant flow — Months 36-48: Romosozumab Retreatment
Milestone	Month 36-48: Placebo/Placebo/Romosozumab	Month 36-48: Placebo/Denosumab/Romosozumab	Month 36-48: Romosozumab/Placebo/Romosozumab	Month 36-48: Romosozumab/Denosumab/Romosozumab
Started	12	16	72	67
Received romosozumab	12	16	72	67
Completed	12	14	65	64
Not completed	0	2	7	3
Withdrew: Adverse event	0	1	3	0
Withdrew: Withdrawal by subject	0	1	2	2
Withdrew: Lost to follow-up	0	0	1	0
Withdrew: Other	0	0	0	1
Withdrew: Continuing the re-treatment phase	0	0	1	0

Months 48-72: Follow-on Phase

Participant flow — Months 48-72: Follow-on Phase
Milestone	Month 48-72: Romosozumab/Denosumab/Romosozumab/No Intervention	Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Placebo/Denosumab/Romosozumab/Zoledronic Acid	Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic Acid
Started	51	11	12	59	8
Received zoledronic acid	0	11	12	56	8
Completed	50	11	12	57	8
Not completed	1	0	0	2	0
Withdrew: Death	1	0	0	0	0
Withdrew: Ineligibility determined	0	0	0	1	0
Withdrew: Withdrawal by subject	0	0	0	1	0

Outcome measures

PrimaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Romosozumab Monthly	Romosozumab Every 3 Months	Romosozumab 140 mg	Romosozumab 210 mg
Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine	-0.1 (-1.2 to 0.9)	4.1 (3.0 to 5.1)	7.1 (6.1 to 8.2)	5.4 (4.3 to 6.4)	5.4 (4.4 to 6.5)	9.1 (8.0 to 10.2)	5.5 (4.4 to 6.6)	11.3 (10.3 to 12.4)	8.6 (7.9 to 9.3)	5.5 (4.7 to 6.3)	7.3 (6.4 to 8.1)	8.4 (7.6 to 9.2)

Statistical analysis

Placebo vs Romosozumab Monthly · Linear Mixed Effects Model · p = < 0.0001 (P-value is adjusted by the Hochberg procedure for comparisons to placebo.) · Ls mean difference from placebo: 8.7 · 95% CI 7.5 to 9.9
Placebo vs Romosozumab Every 3 Months · Linear Mixed Effects Model · p = < 0.0001 (P-value is adjusted by the Hochberg procedure for comparisons to placebo.) · Ls mean difference from placebo: 5.6 · 95% CI 4.3 to 6.9
Placebo vs Romosozumab 140 mg · Linear Mixed Effects Model · p = < 0.0001 (P-value is adjusted by the Hochberg procedure for comparisons to placebo.) · Ls mean difference from placebo: 7.4 · 95% CI 6.1 to 8.7
Placebo vs Romosozumab 210 mg · Linear Mixed Effects Model · p = < 0.0001 (P-value is adjusted by the Hochberg procedure for comparisons to placebo.) · Ls mean difference from placebo: 8.5 · 95% CI 7.3 to 9.8

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine	0.3 (-0.7 to 1.3)	2.6 (1.6 to 3.6)	4.8 (3.8 to 5.8)	4.1 (3.1 to 5.1)	4.2 (3.2 to 5.2)	7.1 (6.1 to 8.1)	4.4 (3.4 to 5.3)	8.2 (7.3 to 9.2)

SecondaryPercent Change From Baseline at Month 6 in BMD of the Total Hip

Time frame:: Baseline to 6 months
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 6 in BMD of the Total Hip
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 6 in BMD of the Total Hip	-0.6 (-1.2 to -0.1)	0.9 (0.3 to 1.5)	0.5 (-0.0 to 1.1)	0.5 (-0.1 to 1.1)	0.9 (0.3 to 1.5)	2.2 (1.7 to 2.8)	1.1 (0.6 to 1.7)	2.9 (2.3 to 3.4)

SecondaryPercent Change From Baseline at Month 6 in BMD of the Femoral Neck

Time frame:: Baseline to 6 months
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck	-0.4 (-1.3 to 0.4)	0.5 (-0.3 to 1.4)	0.5 (-0.3 to 1.3)	0.2 (-0.7 to 1.1)	0.4 (-0.4 to 1.3)	2.1 (1.3 to 3.0)	0.9 (0.1 to 1.7)	1.9 (1.0 to 2.7)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 12 in BMD of the Total Hip
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 12 in BMD of the Total Hip	-0.7 (-1.4 to -0.1)	1.9 (1.3 to 2.6)	1.3 (0.7 to 2.0)	1.3 (0.6 to 2.0)	1.3 (0.7 to 2.0)	3.4 (2.7 to 4.1)	1.9 (1.3 to 2.6)	4.1 (3.5 to 4.8)

SecondaryPercent Change From Baseline at Month 12 in BMD of the Femoral Neck

Time frame:: Baseline to 12 months
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck	-1.1 (-2.0 to -0.2)	1.2 (0.3 to 2.1)	1.1 (0.2 to 2.0)	0.6 (-0.3 to 1.6)	1.8 (0.9 to 2.7)	4.2 (3.3 to 5.1)	1.4 (0.5 to 2.3)	3.7 (2.8 to 4.6)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline at Month 12 in BMD of the Distal Radius
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Percent Change From Baseline at Month 12 in BMD of the Distal Radius	-0.9 (-1.8 to 0.1)	-0.3 (-1.2 to 0.7)	-1.7 (-2.7 to -0.7)	-1.8 (-2.8 to -0.8)	-1.1 (-2.1 to -0.2)	-1.0 (-2.0 to -0.0)	-0.4 (-1.3 to 0.5)	-1.2 (-2.1 to -0.2)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Month 1	-0.7 (-8.7 to 8.1)	—	—	24.2 (14.1 to 35.3)	61.4 (48.6 to 75.3)	55.0 (42.2 to 69.0)	75.8 (61.8 to 90.9)	92.2 (76.6 to 109.1)
Month 3	-5.4 (-13.6 to 3.6)	-50.8 (-55.1 to -46.2)	97.1 (79.7 to 116.1)	-9.1 (-17.1 to -0.2)	-15.5 (-22.7 to -7.7)	3.8 (-5.4 to 13.9)	-19.5 (-26.4 to -12.1)	25.6 (14.6 to 37.5)
Month 6	-5.9 (-14.6 to 3.6)	-57.0 (-61.0 to -52.7)	138.0 (115.7 to 162.6)	-20.0 (-27.7 to -11.4)	-22.8 (-29.9 to -15.0)	-18.6 (-26.3 to -10.1)	-25.5 (-32.2 to -18.1)	6.9 (-3.0 to 17.8)
Month 9	-10.6 (-19.6 to -0.7)	-60.8 (-64.7 to -56.5)	116.8 (95.1 to 140.9)	-26.9 (-34.4 to -18.5)	-23.8 (-31.4 to -15.4)	-26.1 (-33.6 to -17.8)	-30.1 (-36.8 to -22.6)	-5.8 (-15.1 to 4.6)
Month 12	-8.7 (-17.9 to 1.5)	-60.8 (-64.7 to -56.4)	98.3 (78.3 to 120.5)	-23.0 (-31.0 to -14.0)	-23.3 (-30.9 to -14.9)	-31.2 (-38.2 to -23.4)	-29.7 (-36.7 to -22.1)	-17.2 (-25.4 to -8.1)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Month 1	-3.9 (-12.1 to 5.1)	—	—	-22.1 (-28.9 to -14.7)	-19.2 (-26.0 to -11.7)	-35.4 (-41.0 to -29.2)	-33.0 (-38.6 to -26.8)	-28.5 (-34.7 to -21.8)
Month 3	-2.4 (-12.0 to 8.2)	-65.0 (-68.5 to -61.1)	69.4 (52.6 to 88.0)	-21.5 (-29.3 to -12.8)	-6.2 (-15.2 to 3.8)	-26.5 (-33.8 to -18.3)	-12.6 (-21.0 to -3.4)	-3.7 (-13.2 to 6.7)
Month 6	2.7 (-8.4 to 15.2)	-64.2 (-68.1 to -59.8)	93.5 (72.3 to 117.4)	-18.1 (-27.3 to -7.7)	-8.4 (-18.3 to 2.7)	-24.6 (-33.0 to -15.2)	-10.5 (-20.0 to 0.0)	-8.7 (-18.6 to 2.4)
Month 9	1.0 (-11.2 to 14.9)	-64.4 (-68.6 to -59.5)	81.3 (59.4 to 106.2)	-15.1 (-25.7 to -3.0)	1.3 (-10.8 to 15.1)	-27.7 (-36.6 to -17.6)	-11.7 (-22.0 to -0.1)	-17.2 (-27.1 to -6.0)
Month 12	9.8 (-3.9 to 25.4)	-66.7 (-70.8 to -62.0)	77.0 (54.9 to 102.1)	-20.3 (-30.6 to -8.6)	12.2 (-1.5 to 27.8)	-33.0 (-41.4 to -23.3)	-6.6 (-18.0 to 6.5)	-22.5 (-32.0 to -11.7)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Osteocalcin
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Month 1	-1.6 (-9.1 to 6.5)	—	—	28.1 (18.3 to 38.7)	60.1 (48.2 to 73.0)	53.1 (41.2 to 65.9)	77.9 (64.7 to 92.2)	78.6 (65.0 to 93.2)
Month 3	4.1 (-5.6 to 14.7)	-28.7 (-35.3 to -21.5)	104.7 (85.5 to 125.9)	-0.3 (-9.8 to 10.1)	-5.6 (-14.2 to 3.8)	15.6 (4.7 to 27.7)	-3.7 (-12.5 to 5.9)	41.6 (28.4 to 56.1)
Month 6	-7.1 (-16.2 to 2.8)	-40.6 (-46.3 to -34.2)	106.7 (86.5 to 129.1)	-11.8 (-20.8 to -1.8)	-16.5 (-24.5 to -7.6)	-7.4 (-16.5 to 2.8)	-23.2 (-30.5 to -15.3)	10.0 (-0.7 to 21.7)
Month 9	-6.0 (-15.0 to 4.0)	-50.9 (-55.6 to -45.8)	99.9 (80.8 to 121.0)	-26.9 (-34.1 to -18.9)	-29.0 (-35.8 to -21.6)	-27.7 (-34.7 to -19.9)	-30.7 (-37.1 to -23.7)	-4.0 (-13.1 to 6.0)
Month 12	-14.1 (-22.0 to -5.4)	-50.3 (-54.8 to -45.4)	91.6 (74.1 to 110.9)	-27.3 (-34.1 to -19.6)	-24.7 (-31.4 to -17.2)	-31.1 (-37.5 to -24.1)	-26.2 (-32.9 to -18.9)	-12.5 (-20.4 to -3.9)

SecondaryPercent 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
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
percent change	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM
Month 1	-1.1 (-6.7 to 4.9)	—	—	11.7 (5.2 to 18.5)	35.1 (27.5 to 43.1)	29.3 (21.8 to 37.3)	47.5 (39.3 to 56.2)	60.9 (51.7 to 70.7)
Month 3	-7.6 (-14.3 to -0.3)	-30.5 (-35.5 to -25.0)	21.8 (12.8 to 31.4)	-8.5 (-15.3 to -1.1)	-18.0 (-23.9 to -11.7)	1.3 (-6.2 to 9.4)	-17.3 (-23.2 to -10.9)	27.4 (18.1 to 37.4)
Month 6	-4.1 (-12.1 to 4.5)	-35.4 (-40.8 to -29.7)	29.8 (19.0 to 41.6)	-8.7 (-16.6 to -0.1)	-18.2 (-25.0 to -10.9)	-6.6 (-14.5 to 2.0)	-20.0 (-26.4 to -13.0)	13.1 (3.8 to 23.3)
Month 9	3.5 (-3.8 to 11.4)	-32.5 (-37.3 to -27.4)	41.8 (31.7 to 52.6)	-4.9 (-11.9 to 2.6)	-12.5 (-18.7 to -5.9)	-5.5 (-12.3 to 1.8)	-17.7 (-23.3 to -11.7)	10.4 (2.7 to 18.8)
Month 12	9.2 (1.7 to 17.2)	-31.2 (-35.9 to -26.2)	45.7 (35.7 to 56.4)	-2.6 (-9.5 to 4.8)	-10.8 (-16.9 to -4.4)	-5.0 (-11.6 to 2.1)	-12.4 (-18.3 to -6.1)	9.2 (1.8 to 17.1)

Adverse events

Collected over Adverse events are reported by treatment phase: Romosozumab treatment phase (Baseline [BL] to month 12 and 24); Denosumab extension phase (months 24 to 36); Romosozumab retreatment phase (months 36 to 48); Follow-on phase (months 48 to 72).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
BL-Month 12: Placebo QM	—	3/30 (10%)	25/30 (83.3%)
BL-Month 12: Placebo Q3M	—	4/20 (20%)	19/20 (95%)
BL-Month 12: Alendronate	—	4/51 (7.8%)	38/51 (74.5%)
BL-Month12: Teriparatide	—	5/54 (9.3%)	36/54 (66.7%)
BL-Month 12: Romosozumab 70 mg QM	—	5/50 (10%)	46/50 (92%)
BL-Month 12: Romosozumab 140 mg Q3M	—	3/52 (5.8%)	40/52 (76.9%)
BL-Month 12: Romosozumab 140 mg QM	—	2/49 (4.1%)	41/49 (83.7%)
BL-Month 12: Romosozumab 210 mg Q3M	—	3/53 (5.7%)	45/53 (84.9%)
BL-Month 12: Romosozumab 210 mg QM	—	6/51 (11.8%)	40/51 (78.4%)
BL-Month 24: Placebo QM	—	5/30 (16.7%)	28/30 (93.3%)
BL-Month 24: Placebo Q3M	—	4/20 (20%)	20/20 (100%)
BL-Month 24: ALN/Romosozumab 140 mg QM	—	8/51 (15.7%)	49/51 (96.1%)
BL-Month 24: Romosozumab 70 mg QM	—	9/50 (18%)	48/50 (96%)
BL-Month 24: Romosozumab 140 mg Q3M	—	8/52 (15.4%)	47/52 (90.4%)
BL-Month 24: Romosozumab 140 mg QM	—	8/49 (16.3%)	46/49 (93.9%)
BL-Month 24: Romosozumab 210 mg Q3M	—	6/53 (11.3%)	51/53 (96.2%)
BL-Month 24: Romosozumab 210 mg QM	—	7/51 (13.7%)	47/51 (92.2%)
Month 24-36: Placebo/Placebo	—	2/18 (11.1%)	15/18 (83.3%)
Month 24-36: Placebo/Denosumab	—	1/17 (5.9%)	15/17 (88.2%)
Month 24-36: ALN/Romosozumab/Placebo	—	2/19 (10.5%)	12/19 (63.2%)
Month 24-36: ALN/Romosozumab/Denosumab	—	0/19 (0%)	15/19 (78.9%)
Month 24-36: Romosozumab/Placebo	—	3/90 (3.3%)	57/90 (63.3%)
Month 24-36: Romosozumab/Denosumab	—	8/89 (9%)	59/89 (66.3%)
Month 36-48: Placebo/Placebo/Romosozumab	—	0/12 (0%)	12/12 (100%)
Month 36-48: Placebo/Denosumab/Romosozumab	—	1/15 (6.7%)	11/15 (73.3%)
Month 36-48: Romosozumab/Placebo/Romosozumab	—	4/72 (5.6%)	53/72 (73.6%)
Month 36-48: Romosozumab/Denosumab/Romosozumab	—	3/68 (4.4%)	55/68 (80.9%)
Month 48-72: Romosozumab/Denosumab/Romosozumab/No Intervention	—	8/51 (15.7%)	34/51 (66.7%)
Month 48-72: Romosozumab/Placebo/Romosozumab/No	—	0/3 (0%)	1/3 (33.3%)
Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic Acid	—	1/11 (9.1%)	10/11 (90.9%)
Month 48-72: Placebo/Denosumab/Romosozumab/Zoledronic	—	1/12 (8.3%)	8/12 (66.7%)
Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic Acid	—	9/56 (16.1%)	44/56 (78.6%)
Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic Acid	—	1/8 (12.5%)	7/8 (87.5%)

Most frequent serious events

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Most frequent serious events
Event	BL-Month 12: Placebo QM	BL-Month 12: Placebo Q3M	BL-Month 12: Alendronate	BL-Month12: Teriparatide	BL-Month 12: Romosozumab 70 mg QM	BL-Month 12: Romosozumab 140 mg Q3M	BL-Month 12: Romosozumab 140 mg QM	BL-Month 12: Romosozumab 210 mg Q3M	BL-Month 12: Romosozumab 210 mg QM	BL-Month 24: Placebo QM	BL-Month 24: Placebo Q3M	BL-Month 24: ALN/Romosozumab 140 mg QM	BL-Month 24: Romosozumab 70 mg QM	BL-Month 24: Romosozumab 140 mg Q3M	BL-Month 24: Romosozumab 140 mg QM	BL-Month 24: Romosozumab 210 mg Q3M	BL-Month 24: Romosozumab 210 mg QM	Month 24-36: Placebo/Placebo	Month 24-36: Placebo/Denosumab	Month 24-36: ALN/Romosozumab/Placebo	Month 24-36: ALN/Romosozumab/Denosumab	Month 24-36: Romosozumab/Placebo	Month 24-36: Romosozumab/Denosumab	Month 36-48: Placebo/Placebo/Romosozumab	Month 36-48: Placebo/Denosumab/Romosozumab	Month 36-48: Romosozumab/Placebo/Romosozumab	Month 36-48: Romosozumab/Denosumab/Romosozumab	Month 48-72: Romosozumab/Denosumab/Romosozumab/No Intervention	Month 48-72: Romosozumab/Placebo/Romosozumab/No	Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Placebo/Denosumab/Romosozumab/Zoledronic	Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic Acid
Radius fractureInjury, poisoning and procedural complications	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	1/51	1/30	0/20	0/51	0/50	0/52	0/49	0/53	1/51	0/18	0/17	0/19	0/19	0/90	1/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	0/12	0/56	1/8
Peritoneal haemorrhageGastrointestinal disorders	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	1/11	0/12	0/56	0/8
AppendicitisInfections and infestations	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	1/52	1/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	1/11	0/12	0/56	0/8
Respiratory distressRespiratory, thoracic and mediastinal disorders	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	1/11	0/12	0/56	0/8
IridocyclitisEye disorders	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	1/12	0/56	0/8
Thyroid cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	1/15	0/72	0/68	0/51	0/3	0/11	0/12	0/56	0/8
DiverticulitisInfections and infestations	0/30	0/20	0/51	0/54	1/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	1/50	0/52	0/49	0/53	0/51	0/18	1/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	0/12	0/56	0/8
KetoacidosisMetabolism and nutrition disorders	0/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	1/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	0/12	0/56	0/8
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/30	1/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	0/30	1/20	0/51	0/50	0/52	0/49	0/53	0/51	1/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	0/12	0/56	0/8
PneumoniaInfections and infestations	0/30	0/20	0/51	0/54	0/50	1/52	0/49	0/53	0/51	0/30	0/20	0/51	1/50	1/52	1/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	0/3	0/11	0/12	3/56	0/8

Most frequent other events

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Most frequent other events
Event	BL-Month 12: Placebo QM	BL-Month 12: Placebo Q3M	BL-Month 12: Alendronate	BL-Month12: Teriparatide	BL-Month 12: Romosozumab 70 mg QM	BL-Month 12: Romosozumab 140 mg Q3M	BL-Month 12: Romosozumab 140 mg QM	BL-Month 12: Romosozumab 210 mg Q3M	BL-Month 12: Romosozumab 210 mg QM	BL-Month 24: Placebo QM	BL-Month 24: Placebo Q3M	BL-Month 24: ALN/Romosozumab 140 mg QM	BL-Month 24: Romosozumab 70 mg QM	BL-Month 24: Romosozumab 140 mg Q3M	BL-Month 24: Romosozumab 140 mg QM	BL-Month 24: Romosozumab 210 mg Q3M	BL-Month 24: Romosozumab 210 mg QM	Month 24-36: Placebo/Placebo	Month 24-36: Placebo/Denosumab	Month 24-36: ALN/Romosozumab/Placebo	Month 24-36: ALN/Romosozumab/Denosumab	Month 24-36: Romosozumab/Placebo	Month 24-36: Romosozumab/Denosumab	Month 36-48: Placebo/Placebo/Romosozumab	Month 36-48: Placebo/Denosumab/Romosozumab	Month 36-48: Romosozumab/Placebo/Romosozumab	Month 36-48: Romosozumab/Denosumab/Romosozumab	Month 48-72: Romosozumab/Denosumab/Romosozumab/No Intervention	Month 48-72: Romosozumab/Placebo/Romosozumab/No	Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Placebo/Denosumab/Romosozumab/Zoledronic	Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic Acid	Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic Acid
NasopharyngitisInfections and infestations	4/30	3/20	3/51	4/54	19/50	10/52	13/49	5/53	9/51	8/30	4/20	10/51	20/50	14/52	17/49	10/53	14/51	1/18	1/17	3/19	4/19	7/90	10/89	3/12	3/15	8/72	11/68	4/51	0/3	2/11	2/12	4/56	2/8
Oral fungal infectionInfections and infestations	2/30	0/20	0/51	0/54	0/50	0/52	0/49	0/53	0/51	2/30	0/20	0/51	0/50	0/52	0/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	1/3	0/11	0/12	0/56	0/8
Respiratory tract infectionInfections and infestations	0/30	0/20	0/51	0/54	1/50	0/52	0/49	0/53	0/51	0/30	0/20	0/51	2/50	0/52	0/49	0/53	0/51	1/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	0/72	0/68	0/51	1/3	0/11	0/12	1/56	0/8
SinusitisInfections and infestations	1/30	1/20	1/51	0/54	3/50	0/52	2/49	2/53	2/51	1/30	2/20	3/51	7/50	2/52	4/49	6/53	7/51	0/18	0/17	0/19	0/19	2/90	3/89	0/12	0/15	3/72	0/68	1/51	1/3	0/11	0/12	0/56	0/8
Tooth infectionInfections and infestations	2/30	0/20	0/51	0/54	1/50	0/52	1/49	0/53	0/51	2/30	0/20	2/51	1/50	0/52	1/49	0/53	0/51	0/18	0/17	0/19	0/19	0/90	0/89	0/12	0/15	1/72	0/68	0/51	1/3	0/11	0/12	0/56	0/8
FallInjury, poisoning and procedural complications	1/30	0/20	4/51	1/54	2/50	3/52	2/49	1/53	1/51	2/30	0/20	7/51	4/50	3/52	7/49	3/53	4/51	1/18	0/17	1/19	1/19	3/90	4/89	0/12	1/15	3/72	4/68	0/51	1/3	0/11	0/12	4/56	2/8
ArthralgiaMusculoskeletal and connective tissue disorders	3/30	0/20	4/51	5/54	8/50	7/52	6/49	5/53	2/51	8/30	3/20	11/51	10/50	8/52	6/49	9/53	6/51	1/18	0/17	1/19	3/19	2/90	6/89	2/12	0/15	6/72	11/68	1/51	1/3	1/11	0/12	8/56	2/8
MyalgiaMusculoskeletal and connective tissue disorders	2/30	1/20	1/51	1/54	2/50	0/52	1/49	2/53	1/51	4/30	2/20	3/51	3/50	1/52	1/49	2/53	1/51	0/18	0/17	0/19	3/19	0/90	2/89	0/12	1/15	2/72	4/68	0/51	1/3	0/11	3/12	7/56	2/8
Influenza like illnessGeneral disorders	0/30	0/20	0/51	0/54	0/50	2/52	0/49	0/53	2/51	0/30	0/20	1/51	2/50	2/52	0/49	1/53	3/51	1/18	0/17	0/19	0/19	1/90	0/89	0/12	1/15	0/72	1/68	0/51	0/3	3/11	2/12	9/56	0/8
InfluenzaInfections and infestations	2/30	2/20	3/51	3/54	2/50	1/52	1/49	2/53	4/51	5/30	3/20	10/51	7/50	3/52	4/49	5/53	8/51	0/18	1/17	0/19	1/19	2/90	4/89	3/12	1/15	8/72	7/68	1/51	0/3	0/11	2/12	8/56	1/8

Baseline characteristics

All randomized participants (full analysis set)

Age, Continuous
Age, Continuous(years)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Mean	67.0 ± 6.5	67.1 ± 5.8	66.8 ± 5.7	65.8 ± 6.1	67.3 ± 6.7	67.8 ± 6.2	66.1 ± 7.3	66.3 ± 6.5	66.8 ± 6.4

Age, Customized
Age, Customized(Participants)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
< 65 years	20	18	21	21	20	12	24	18	154
≥ 65 years	32	33	34	30	34	39	29	34	265

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Female	52	51	55	51	54	51	53	52	419
Male	0	0	0	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
White or Caucasian	47	46	44	46	43	48	44	44	362
Black or African American	0	0	1	0	2	0	0	0	3
Hispanic or Latino	5	4	9	5	8	3	8	6	48
Asian	0	1	1	0	0	0	1	1	4
Japanese	0	0	0	0	0	0	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	0	0	0	1

Lumbar Spine Bone Mineral Density (BMD) T-score
Lumbar Spine Bone Mineral Density (BMD) T-score(T-score)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Mean	-2.29 ± 0.66	-2.08 ± 0.69	-2.29 ± 0.57	-2.35 ± 0.79	-2.44 ± 0.70	-2.27 ± 0.77	-2.21 ± 0.69	-2.33 ± 0.57	-2.29 ± 0.68

Total Hip BMD T-score
Total Hip BMD T-score(T-score)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Mean	-1.35 ± 0.67	-1.55 ± 0.68	-1.32 ± 0.78	-1.69 ± 0.67	-1.58 ± 0.51	-1.67 ± 0.65	-1.65 ± 0.63	-1.45 ± 0.65	-1.53 ± 0.66

Femoral Neck BMD T-score
Femoral Neck BMD T-score(T-score)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Mean	-1.76 ± 0.56	-1.91 ± 0.61	-1.79 ± 0.67	-2.06 ± 0.55	-2.00 ± 0.54	-2.03 ± 0.58	-2.02 ± 0.57	-1.87 ± 0.58	-1.93 ± 0.59

Distal 1/3 Radius BMD T-score
Distal 1/3 Radius BMD T-score(T-score)	Placebo	Alendronate	Teriparatide	Romosozumab 70 mg QM	Romosozumab 140 mg Q3M	Romosozumab 140 mg QM	Romosozumab 210 mg Q3M	Romosozumab 210 mg QM	Total
Mean	-1.85 ± 1.04	-2.08 ± 0.99	-2.05 ± 1.21	-1.78 ± 1.14	-2.24 ± 1.06	-2.11 ± 1.12	-1.98 ± 1.04	-2.03 ± 0.99	-2.01 ± 1.08

4 further baseline measures are reported on the registry.

Study locations

No study locations are listed for this record.

References and documents

Publications

Genant HK, Engelke K, Bolognese MA, Mautalen C, Brown JP, Recknor C, Goemaere S, Fuerst T, Yang YC, Grauer A, Libanati C. Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Jan;32(1):181-187. doi: 10.1002/jbmr.2932. Epub 2016 Sep 20. PubMed 27487526 ↗
Keaveny TM, Crittenden DB, Bolognese MA, Genant HK, Engelke K, Oliveri B, Brown JP, Langdahl BL, Yan C, Grauer A, Libanati C. Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Sep;32(9):1956-1962. doi: 10.1002/jbmr.3176. Epub 2017 Jun 26. PubMed 28543940 ↗
Kendler DL, Bone HG, Massari F, Gielen E, Palacios S, Maddox J, Yan C, Yue S, Dinavahi RV, Libanati C, Grauer A. Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. Osteoporos Int. 2019 Dec;30(12):2437-2448. doi: 10.1007/s00198-019-05146-9. Epub 2019 Oct 18. PubMed 31628490 ↗
McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, Bolognese MA, Goemaere S, Bone HG, Zanchetta JR, Maddox J, Bray S, Grauer A. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. J Bone Miner Res. 2018 Aug;33(8):1397-1406. doi: 10.1002/jbmr.3452. Epub 2018 May 22. PubMed 29694685 ↗
McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Maddox J, Shi Y, Rojeski M, Meisner PD, Grauer A. A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab. Osteoporos Int. 2020 Nov;31(11):2231-2241. doi: 10.1007/s00198-020-05502-0. Epub 2020 Jul 4. PubMed 32623487 ↗
McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Shi Y, Timoshanko J, Libanati C, Chines A, Oates MK. Skeletal responses to romosozumab after 12 months of denosumab. JBMR Plus. 2021 Jun 3;5(7):e10512. doi: 10.1002/jbm4.10512. eCollection 2021 Jul. PubMed 34258507 ↗
Poole KE, Treece GM, Pearson RA, Gee AH, Bolognese MA, Brown JP, Goemaere S, Grauer A, Hanley DA, Mautalen C, Recknor C, Yang YC, Rojeski M, Libanati C, Whitmarsh T. Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density. J Bone Miner Res. 2022 Feb;37(2):256-264. doi: 10.1002/jbmr.4465. Epub 2021 Dec 16. PubMed 34738660 ↗
McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014 Jan 30;370(5):412-20. doi: 10.1056/NEJMoa1305224. Epub 2014 Jan 1. PubMed 24382002 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 22, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00896532
Lead sponsor: Amgen
Responsible party: Sponsor
First posted: May 11, 2009
Start date: Jun 3, 2009
Primary completion: Feb 21, 2011
Completion: Feb 18, 2016
Results posted: Dec 14, 2018
Last update: Sep 22, 2022

Study contacts

study director · Amgen

Oversight

Data monitoring committee: No

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Studies of the drugs tested here: Romosozumab · Denosumab · Zoledronic Acid

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