Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT00896532Other id20060326Other id2008-005991-28Other id2008

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 2
Enrollment: 419 participants (actual)
Sponsor: Amgen · Industry
Design: Randomized · Quadruple masking
Countries: Not stated
Start: 3 Jun 2009
Primary completion: 21 Feb 2011
Completion: 18 Feb 2016
First posted: 11 May 2009 (estimated)
Last update posted: 22 Sept 2022
Conditions: Low Bone Mineral Density · Postmenopausal Osteoporosis

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2010201220142016

Ph 2
Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density
NCT00896532
3 Jun 2009 to 18 Feb 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Placebo to RomosozumabDrug
AlendronateDrug
TeriparatideDrug
RomosozumabDrug
DenosumabDrug
Placebo to DenosumabDrug
Zoledronic acidDrug

Arms8

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.
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.
Active comparator
Teriparatide
Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.
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.
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.
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.
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.
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.

Primary outcomes1

Outcomes the sponsor listed as primary.

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine
Time frame · Baseline to 12 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.

Secondary outcomes(10)

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
Time frame · Baseline to 6 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 6 in BMD of the Total Hip
Time frame · Baseline to 6 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
Time frame · Baseline to 6 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Total Hip
Time frame · Baseline to 12 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
Time frame · Baseline to 12 months
Registry description
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Distal Radius
Time frame · Baseline to 12 months
Registry description
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.
Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Registry description
Percent change from baseline in the bone turnover marker (BTM) P1NP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Registry description
Percent change from baseline in the bone turnover marker (BTM) CTX was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Osteocalcin
Time frame · Baseline and months 1, 3, 6, 9, and 12
Registry description
Percent change from baseline in the bone turnover marker (BTM) osteocalcin was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline to 12 months

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine

Group	Value (percent change)
Placebo	-0.1
Alendronate	4.1
Teriparatide	7.1
Romosozumab 70 mg QM	5.4
Romosozumab 140 mg Q3M	5.4
Romosozumab 140 mg QM	9.1
Romosozumab 210 mg Q3M	5.5
Romosozumab 210 mg QM	11.3
Romosozumab Monthly	8.6
Romosozumab Every 3 Months	5.5
Romosozumab 140 mg	7.3
Romosozumab 210 mg	8.4

Secondary and other outcome results(7)

Secondary outcomeLeast squares mean· Baseline to 6 months

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine

Group	Value (percent change)
Placebo	0.3
Alendronate	2.6
Teriparatide	4.8
Romosozumab 70 mg QM	4.1
Romosozumab 140 mg Q3M	4.2
Romosozumab 140 mg QM	7.1
Romosozumab 210 mg Q3M	4.4
Romosozumab 210 mg QM	8.2

Secondary outcomeLeast squares mean· Baseline to 6 months

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

Group	Value (percent change)
Placebo	-0.6
Alendronate	0.9
Teriparatide	0.5
Romosozumab 70 mg QM	0.5
Romosozumab 140 mg Q3M	0.9
Romosozumab 140 mg QM	2.2
Romosozumab 210 mg Q3M	1.1
Romosozumab 210 mg QM	2.9

Secondary outcomeLeast squares mean· Baseline to 6 months

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

Group	Value (percent change)
Placebo	-0.4
Alendronate	0.5
Teriparatide	0.5
Romosozumab 70 mg QM	0.2
Romosozumab 140 mg Q3M	0.4
Romosozumab 140 mg QM	2.1
Romosozumab 210 mg Q3M	0.9
Romosozumab 210 mg QM	1.9

Secondary outcomeLeast squares mean· Baseline to 12 months

Percent Change From Baseline at Month 12 in BMD of the Total Hip

Group	Value (percent change)
Placebo	-0.7
Alendronate	1.9
Teriparatide	1.3
Romosozumab 70 mg QM	1.3
Romosozumab 140 mg Q3M	1.3
Romosozumab 140 mg QM	3.4
Romosozumab 210 mg Q3M	1.9
Romosozumab 210 mg QM	4.1

Secondary outcomeLeast squares mean· Baseline to 12 months

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

Group	Value (percent change)
Placebo	-1.1
Alendronate	1.2
Teriparatide	1.1
Romosozumab 70 mg QM	0.6
Romosozumab 140 mg Q3M	1.8
Romosozumab 140 mg QM	4.2
Romosozumab 210 mg Q3M	1.4
Romosozumab 210 mg QM	3.7

Secondary outcomeLeast squares mean· Baseline to 12 months

Percent Change From Baseline at Month 12 in BMD of the Distal Radius

Group	Value (percent change)
Placebo	-0.9
Alendronate	-0.3
Teriparatide	-1.7
Romosozumab 70 mg QM	-1.8
Romosozumab 140 mg Q3M	-1.1
Romosozumab 140 mg QM	-1.0
Romosozumab 210 mg Q3M	-0.4
Romosozumab 210 mg QM	-1.2

Secondary outcomeLeast squares mean· Baseline and months 1, 3, 6, 9, and 12

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)

Group	Value (percent change)
Placebo	-0.7
Alendronate	not posted
Teriparatide	not posted
Romosozumab 70 mg QM	24.2
Romosozumab 140 mg Q3M	61.4
Romosozumab 140 mg QM	55.0
Romosozumab 210 mg Q3M	75.8
Romosozumab 210 mg QM	92.2

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
BL-Month 12: Placebo QMParticipants received placebo matching to romosozumab once a month (QM) administered subcutaneously for 12 months.	–	3 / 30	25 / 30
BL-Month 12: Placebo Q3MParticipants received placebo matching to romosozumab once every 3 months (Q3M) administered subcutaneously for 12 months.	–	4 / 20	19 / 20
BL-Month 12: AlendronateParticipants received open-label alendronate (ALN) 70 mg orally (PO) every week (QW) for 12 months.	–	4 / 51	38 / 51
BL-Month12: TeriparatideParticipants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months.	–	5 / 54	36 / 54
BL-Month 12: Romosozumab 70 mg QMParticipants received double-blind romosozumab 70 mg subcutaneously every month for 12 months.	–	5 / 50	46 / 50
BL-Month 12: Romosozumab 140 mg Q3MParticipants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 12 months.	–	3 / 52	40 / 52
BL-Month 12: Romosozumab 140 mg QMParticipants received double-blind romosozumab 140 mg subcutaneously every month for 12 months.	–	2 / 49	41 / 49
BL-Month 12: Romosozumab 210 mg Q3MParticipants received double-blind romosozumab 210 mg Q3M subcutaneously for 12 months.	–	3 / 53	45 / 53
BL-Month 12: Romosozumab 210 mg QMParticipants received double-blind romosozumab 210 mg QM subcutaneously for 12 months.	–	6 / 51	40 / 51
BL-Month 24: Placebo QMParticipants received placebo matching to romosozumab QM administered subcutaneously for 24 months.	–	5 / 30	28 / 30
BL-Month 24: Placebo Q3MParticipants received placebo matching to romosozumab Q3M administered subcutaneously for 24 months.	–	4 / 20	20 / 20
BL-Month 24: ALN/Romosozumab 140 mg QMParticipants received open-label alendronate (ALN) 70 mg PO 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).	–	8 / 51	49 / 51
BL-Month 24: Romosozumab 70 mg QMParticipants received double-blind romosozumab 70 mg subcutaneously every month for 24 months.	–	9 / 50	48 / 50
BL-Month 24: Romosozumab 140 mg Q3MParticipants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months.	–	8 / 52	47 / 52
BL-Month 24: Romosozumab 140 mg QMParticipants received double-blind romosozumab 140 mg subcutaneously every month for 24 months.	–	8 / 49	46 / 49
BL-Month 24: Romosozumab 210 mg Q3MParticipants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months.	–	6 / 53	51 / 53
BL-Month 24: Romosozumab 210 mg QMParticipants received double-blind romosozumab 210 mg QM subcutaneously for 24 months.	–	7 / 51	47 / 51
Month 24-36: Placebo/PlaceboParticipants who received placebo in the 24-month romosozumab treatment phase then received placebo to denosumab subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	2 / 18	15 / 18
Month 24-36: Placebo/DenosumabParticipants who received placebo in the 24-month romosozumab treatment phase then received denosumab 60 mg subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	1 / 17	15 / 17
Month 24-36: ALN/Romosozumab/PlaceboParticipants who received alendronate for the first 12 months and romosozumab 140 mg subcutaneously every month from months 12 to 24 received placebo to denosumab subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	2 / 19	12 / 19
Month 24-36: ALN/Romosozumab/DenosumabParticipants who received alendronate for the first 12 months, romosozumab 140 mg subcutaneously every month from months 12-24 received denosumab 60 mg subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	0 / 19	15 / 19
Month 24-36: Romosozumab/PlaceboParticipants who received romosozumab at any dose for 24 months in the romosozumab treatment phase received placebo to denosumab subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	3 / 90	57 / 90
Month 24-36: Romosozumab/DenosumabParticipants who received romosozumab at any dose for 24 months in the romosozumab treatment phase received denosumab 60 mg subcutaneously once every 6 months for 12 months during the denosumab extension phase.	–	8 / 89	59 / 89
Month 36-48: Placebo/Placebo/RomosozumabParticipants who received placebo in the first 24-month romosozumab treatment phase and placebo to denosumab during months 24 to 36 then received romosozumab 210 mg subcutaneously QM in the 12-month romosozumab retreatment phase (months 36 to 48).	–	0 / 12	12 / 12
Month 36-48: Placebo/Denosumab/RomosozumabParticipants who received placebo in the first 24-month romosozumab treatment phase and denosumab 60 mg during months 24 to 36 then received romosozumab 210 mg subcutaneously QM in the 12-month romosozumab retreatment phase (months 36 to 48).	–	1 / 15	11 / 15
Month 36-48: Romosozumab/Placebo/RomosozumabParticipants who received romosozumab at any dose during the first 24-month romosozumab treatment phase and placebo to denosumab during months 24 to 36 then received romosozumab 210 mg subcutaneously QM in the 12-month romosozumab retreatment phase (months 36 to 48).	–	4 / 72	53 / 72
Month 36-48: Romosozumab/Denosumab/RomosozumabParticipants who received romosozumab at any dose during the first 24-month romosozumab treatment phase and denosumab 60 mg during months 24 to 36 then received romosozumab 210 mg subcutaneously QM in the 12-month romosozumab retreatment phase (months 36 to 48).	–	3 / 68	55 / 68
Month 48-72: Romosozumab/Denosumab/Romosozumab/No InterventionParticipants who received romosozumab at any dose during the first 24 month treatment phase, denosumab 60 mg during months 24 to 36 and romosozumab 210 mg QM in months 36 to 48 then received no intervention during the 24-month follow-on phase (months 48-72).	–	8 / 51	34 / 51
Month 48-72: Romosozumab/Placebo/Romosozumab/NoParticipants who received romosozumab at any dose during the first 24 month treatment phase, placebo to denosumab during months 24 to 36 and romosozumab 210 mg QM in months 36 to 48 were assigned to the zoledronic acid treatment group, but received no intervention during the 24-month follow-on phase (months 48 to 72).	–	0 / 3	1 / 3
Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic AcidParticipants who received placebo in the 24-month romosozumab treatment phase, placebo to denosumab during months 24 to 36 and romosozumab 210 mg QM in months 36 to 48 then received a single dose of open-label zoledronic acid 5 mg intravenously at month 48.	–	1 / 11	10 / 11
Month 48-72: Placebo/Denosumab/Romosozumab/ZoledronicParticipants who received placebo in the 24-month romosozumab treatment phase, denosumab 60 mg Q6M from months 24 to 36 and romosozumab 210 mg QM from months 36 to 48 then received a single dose of open-label zoledronic acid 5 mg intravenously at month 48.	–	1 / 12	8 / 12
Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic AcidParticipants who received romosozumab at any dose during the 24-month romosozumab treatment phase, placebo to denosumab during months 24 to 36 and romosozumab 210 mg QM in months 36 to 48 then received a single dose of open-label zoledronic acid 5 mg intravenously at month 48.	–	9 / 56	44 / 56
Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic AcidParticipants who received romosozumab at any dose during the 24-month romosozumab treatment phase, denosumab 60 mg Q6M during months 24 to 36 and romosozumab 210 mg QM in months 36 to 48 then received a single dose of open-label zoledronic acid 5 mg intravenously at month 48.	–	1 / 8	7 / 8

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2017

11 results

Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass.

Genant et al. 2017Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchcited by 101

PMID 27487526DOI 10.1002/jbmr.2932PUB-27487526

Rights unknown11 results

Source link See results (11)

Indexing hint: Randomized controlled trial · 2017

2 results

Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass.

Keaveny et al. 2017Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchcited by 74

PMID 28543940DOI 10.1002/jbmr.3176PUB-28543940

Full text at the publisher2 results

Publisher page See results (2)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedMcClung 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. PMID 24382002

Eligibility

Who could join, as posted.

Sex: Female
Age: from 55 Years up to 85 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Ambulatory, postmenopausal women, aged ≥ 55 to ≤ 85 * Low BMD measured by dual energy X-ray absorptiometry (DXA) and assessed by the central imaging vendor (equivalent to T-scores between -2.0 and -3.5) Exclusion Criteria: * History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50 * Untreated hyper- or hypothyroidism * Current hyper- or hypoparathyroidism, hypo- or hypercalcemia * Elevated transaminases * Significantly impaired renal function * Positive for: human immunodeficiency virus (HIV), hepatitis-C or hepatitis-B surface antigen * Malignancy * History of solid organ or bone marrow transplants * Use of agents affecting bone metabolism * Contraindicated or intolerant of alendronate therapy * Contraindicated or intolerant of teriparatide therapy Inclusion Criteria for the 12 month extension phase (Month 24 to 36): \- Normocalcemia at or after the Month 21 visit but before the Month 24 study visit 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

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