Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab

Kendler, David L.; Bone, Henry G.; Massari, Fabio; Gielen, Evelien; Palacios, Santiago; Maddox, Judy; Yan, Chao; Yue, Susan; Dinavahi, Rajani; Libanati, Cesar; Grauer, Andreas

doi:10.1007/s00198-019-05146-9

Cited by 82 publications

(77 citation statements)

References 16 publications

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“…Regarding transitioning from denosumab to osteoanabolic treatment, there is evidence that switching to teriparatide leads to a high bone turnover state and a temporary but rapid decrease in BMD, especially at cortical skeletal sites . Finally, recent evidence has shown that romosozumab treatment after denosumab discontinuation results in BMD gains, albeit of a smaller magnitude compared with romosozumab administration alone in treatment‐naive patients …”

Section: Pharmacologic Osteoporosis Treatmentmentioning

confidence: 99%

Osteoporosis Management in the Era of COVID-19

Tsourdi

Clarke

et al. 2020

Journal of Bone and Mineral Research

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Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available.

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Section: Pharmacologic Osteoporosis Treatmentmentioning

confidence: 99%

Osteoporosis Management in the Era of COVID-19

Tsourdi

Clarke

et al. 2020

Journal of Bone and Mineral Research

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“…Results of the study periods up to month 48 have been previously published [17,20,26]. This report focuses on results from the month 48 to 72 follow-on period, assessing the exploratory endpoints of the percentage change in BMD at the lumbar spine, total hip, and femoral neck and bone turnover markers (P1NP and β-CTX), and the safety of transitioning to zoledronate after 12 months of treatment with a second course of romosozumab.…”

Section: Study Outcomesmentioning

confidence: 99%

“…In a prior extension of this phase 2 study, subjects received a second course of romosozumab 210 mg QM from months 36 to 48. Rapid and large BMD gains with romosozumab were observed in subjects who had received no active treatment in the 12 months prior [26]. The BMD response to romosozumab following denosumab was very small, but romosozumab prevented BMD declines following denosumab discontinuation.…”

Section: Introductionmentioning

confidence: 98%

A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab

McClung

Bolognese²,

Brown

et al. 2020

Osteoporos Int

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This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. Introduction Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. Methods This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0-24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and β-CTX) and safety were evaluated for 24 months, up to month 72. Results A total of 141 subjects entered the month 48-72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48-72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: − 0.8% from months 48-72; 12.8% from months 0-72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and β-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and β-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. Conclusion A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment.

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“…After ascertaining the waning effect of romosozumab following its cessation, the next extension study evaluated the effect of a second course of romosozumab following a period off treatment or on denosumab [ 92 ]. Thus, participants of [ 91 ] were offered 12 additional months of 210 mg romosozumab per month (translating into months 36–48 of the original Phase II study [ 67 ]).…”

Section: Monoclonal Antibodies Against Sclerostin In Human Osteopomentioning

confidence: 99%

Osteoporosis Treatment with Anti-Sclerostin Antibodies—Mechanisms of Action and Clinical Application

Rauner

Taipaleenmäki

Tsourdi

et al. 2021

JCM

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Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures and significant long-term disability. Although both anti-resorptive treatments and osteoanabolic drugs, such as parathyroid hormone analogues, are effective in fracture prevention, limitations exist due to lack of compliance or contraindications to these drugs. Thus, there is a need for novel potent therapies, especially for patients at high fracture risk. Romosozumab is a monoclonal antibody against sclerostin with a dual mode of action. It enhances bone formation and simultaneously suppresses bone resorption, resulting in a large anabolic window. In this opinion-based narrative review, we highlight the role of sclerostin as a critical regulator of bone mass and present human diseases of sclerostin deficiency as well as preclinical models of genetically modified sclerostin expression, which led to the development of anti-sclerostin antibodies. We review clinical studies of romosozumab in terms of bone mass accrual and anti-fracture activity in the setting of postmenopausal and male osteoporosis, present sequential treatment regimens, and discuss its safety profile and possible limitations in its use. Moreover, an outlook comprising future translational applications of anti-sclerostin antibodies in diseases other than osteoporosis is given, highlighting the clinical significance and future scopes of Wnt signaling in these settings.

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Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab

Cited by 82 publications

References 16 publications

Osteoporosis Management in the Era of COVID-19

Osteoporosis Management in the Era of COVID-19

A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab

Osteoporosis Treatment with Anti-Sclerostin Antibodies—Mechanisms of Action and Clinical Application

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