Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial

Langdahl, Bente; Libanati, Cesar; Crittenden, Daria B.; Bolognese, Michael A.; Brown, Jacques P.; Daizadeh, Nadia; Dokoupilová, Eva; Engelke, Klaus; Finkelstein, Joel S.; Genant, Harry K.; Goemaere, Stefan; Hyldstrup, Lars; Jódar-Gimeno, Esteban; Keaveny, Tony M.; Kendler, David L.; Lakatos, Péter L.; Maddox, Judy; Malouf, Jorge; Massari, Fabio; Molina, José Fernando; Ulla, María Rosa; Grauer, Andreas

doi:10.1016/s0140-6736(17)31613-6

Cited by 348 publications

(323 citation statements)

References 20 publications

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“…The additional gains in BMD observed in this group during the second year of the study (5% at the lumbar spine and 0.7% at the total hip) were only slightly less than observed in treatment‐naïve women who had received that dose of romosozumab during year 1 of the study (5.5% and 1.3% in the lumbar spine and total hip, respectively) . This is consistent with data from a recently published study where 12 months of treatment with romosozumab 210 mg QM, evaluated in phase 3 studies, was compared with treatment with teriparatide 20 μg daily in participants transitioning from oral bisphosphonate and showed greater increases in bone mass and bone strength (by finite element analysis) than treatment with teriparatide.…”

Section: Discussionsupporting

confidence: 90%

“…Therefore, this study does not address the question of how the sequence of a bisphosphonate followed by the recommended dose of romosozumab 210 mg QM compares with the use of an equivalent dose of romosozumab only. However, in a recently published study, patients were transitioned from bisphosphonate treatment to either romosozumab 210 mg QM or teriparatide 20 μg once daily . The BMD increases at the spine and the hip were greater with romosozumab than with teriparatide but were smaller than those observed with romosozumab 210 mg QM in treatment‐naïve populations …”

Section: Discussionmentioning

confidence: 99%

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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

McClung

Brown

Díez-Pérez

et al. 2018

Journal of Bone and Mineral Research

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163

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Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤-2.0 and ≥-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

McClung

Brown

Díez-Pérez

et al. 2018

Journal of Bone and Mineral Research

Self Cite

163

153

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“…In trials of postmenopausal women with osteoporosis, romosozumab increased BMD to a greater extent than existing anabolic agents and decreased vertebral and nonvertebral fractures . In another study, comparing romosozumab to teriparatide, there was a greater increase in cortical BMD (compared with trabecular BMD) in the romosozumab arm compared with a reduction in cortical BMD in the teriparatide group . Increased cardiovascular events were reported in one (but no other) romosozumab study .…”

Section: Osteoanabolic Agentsmentioning

confidence: 93%

Rethinking Bone Disease in Kidney Disease

Damasiewicz

Nickolas

2018

JBMR Plus

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Renal osteodystrophy (ROD) is the bone component of chronic kidney disease mineral and bone disorder (CKD‐MBD). ROD affects bone quality and strength through the numerous hormonal and metabolic disturbances that occur in patients with kidney disease. Collectively these disorders in bone quality increase fracture risk in CKD patients compared with the general population. Fractures are a serious complication of kidney disease and are associated with higher morbidity and mortality compared with the general population. Furthermore, at a population level, fractures are at historically high levels in patients with end‐stage kidney disease (ESKD), whereas in contrast the general population has experienced a steady decline in fracture incidence rates. Based on these findings, it is clear that a paradigm shift is needed in our approach to diagnosing and managing ROD. In clinical practice, our ability to diagnose ROD and initiate antifracture treatments is impeded by the lack of accurate noninvasive methods that identify ROD type. The past decade has seen advances in the noninvasive measurement of bone quality and strength that have been studied in kidney disease patients. Below we review the current literature pertaining to the epidemiology, pathology, diagnosis, and management of ROD. We aim to highlight the pressing need for a greater awareness of this condition and the need for the implementation of strategies that prevent fractures in kidney disease patients. Research is needed for more accurate noninvasive assessment of ROD type, clinical studies of existing osteoporosis therapies in patients across the spectrum of kidney disease, and the development of CKD‐specific treatments. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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“…(66,67) More recently, the post-bisphosphonate skeletal effects of romosozumab were directly compared to teriparatide in a randomized open label trial of postmenopausal osteoporotic women (all subjects had taken bisphosphonates for at least 3 years and alendronate during the year prior to enrollment). (68) In women randomized to teriparatide, hip BMD decreased slightly over 12 months whereas it increased by approximately 3% in those receiving romosozumab. Spine BMD increased in both groups, but significantly more in those treated with romosozumab.…”

Section: Anabolic Agents After Antiresorptive Agentsmentioning

confidence: 99%

“…Moreover, studies have suggested that bisphosphonates with longer skeletal half‐lives may produce a more pronounced blunting than those with more transient biological activity . More recently, the post‐bisphosphonate skeletal effects of romosozumab were directly compared to teriparatide in a randomized open label trial of postmenopausal osteoporotic women (all subjects had taken bisphosphonates for at least 3 years and alendronate during the year prior to enrollment) . In women randomized to teriparatide, hip BMD decreased slightly over 12 months whereas it increased by approximately 3% in those receiving romosozumab.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Sequential and Combined Anabolic and Antiresorptive Osteoporosis Therapy

Leder

2018

JBMR Plus

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As osteoporosis therapy options have expanded, and clinical guidelines have begun to embrace the concept of limited treatment courses and “drug holidays,” the choices that physicians must make when initiating, electing to continue, or switching therapies have become more complex. As a result, one of the fundamental issues that must be carefully considered is whether, when, and in what sequence anabolic therapies should be utilized. This review evaluates the current evidence supporting the optimal sequence for the use of anabolic and antiresorptive drugs and assesses the expanding number of clinical trials favoring the initial use of anabolic therapy followed by an antiresorptive agent. This review also explores the evidence suggesting that the effectiveness of anabolic medications are diminished when used in patients that have been previously treated with specific antiresorptive drugs for prolonged periods. Finally, the recent advances in designing combination antiresorptive/anabolic treatment approaches are detailed, with a focus on combined denosumab/teriparatide regimens, which appear to provide the most substantial and clinically relevant skeletal benefits to patients with established osteoporosis. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial

Cited by 348 publications

References 20 publications

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

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

Rethinking Bone Disease in Kidney Disease

Optimizing Sequential and Combined Anabolic and Antiresorptive Osteoporosis Therapy

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