Abstract
ABSTRACTRomosozumab, a monoclonal anti‐sclerostin antibody that has the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. In a post hoc, exploratory analysis, we evaluated the effects of romosozumab after 12 months of denosumab in postmenopausal women with low bone mass who had not received previous osteoporosis therapy. This phase 2 trial (NCT00896532) enrolled postmenopausal women with a lumbar spine, total hip, or femoral neck T‐score ≤ −2.0 and ≥ −3.5. Individuals were randomized to placebo or various romosozumab dosing regimens from baseline to month 24, were re‐randomized to 12 months of denosumab or placebo (months 24–36), and then all received romosozumab 210 mg monthly for 12 months (months 36–48). Results for the overall population have been previously published. Here, we present results for changes in bone mineral density (BMD) and levels of procollagen type I N‐terminal propeptide (P1NP) and β‐isomer of the C‐terminal telopeptide of type I collagen (β‐CTX) from a subset of women who were randomized to placebo for 24 months, were re‐randomized to receive denosumab (n = 16) or placebo (n = 12) for 12 months, and then received romosozumab for 12 months. In women who were randomized to placebo followed by denosumab, romosozumab treatment for 12 months maintained BMD gained during denosumab treatment at the total hip (mean change from end of denosumab treatment of 0.9%) and further increased BMD gains at the lumbar spine (mean change from end of denosumab treatment of 5.3%). Upon transition to romosozumab (months 36–48), P1NP and β‐CTX levels gradually returned to baseline from their reduced values during denosumab administration. Transitioning to romosozumab after 12 months of denosumab appears to improve lumbar spine BMD and maintain total hip BMD while possibly preventing the rapid increase in levels of bone turnover markers above baseline expected upon denosumab discontinuation. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Highlights
A ntiresorptive drugs and bone-forming agents are distinct classes of therapies for treating patients with osteoporosis.[1]. Estrogen receptor activators, bisphosphonates, and denosumab are anti-remodeling drugs that reduce bone resorption and formation, increase bone mineral density (BMD), improve bone strength and reduce fracture risk, but they do not restore the disordered trabecular microarchitecture found in patients with postmenopausal osteoporosis.[2]. In contrast, bone-forming agents stimulate bone formation, resulting in large increases in BMD and improved bone structure, and have been shown to be more effective at reducing fracture risk than oral bisphosphonates.[3,4,5,6,7] Based on these data, bone forming agents are recommended as appropriate initial treatment for patients at very high risk of fracture.[8,9,10]
Lumbar spine BMD increased an additional 5.3% while taking romosozumab for 12 months for an average cumulative gain of 11.5% over the 24-month denosumab-to-romosozumab treatment period (Figure 2B; Table 2)
The increase in BMD seen with denosumab at the total hip was maintained by 12 months of romosozumab; 0.9% mean change from end of denosumab treatment, for a cumulative gain of 3.8% over the 24-month treatment period with denosumab and romosozumab (Figure 2D; Table 2)
Summary
A ntiresorptive drugs and bone-forming agents are distinct classes of therapies for treating patients with osteoporosis.[1]. Romosozumab, an anti-sclerostin monoclonal antibody, is a bone-forming agent with a novel mechanism of action—a dual effect of activating both modeling-based and remodeling-based bone formation while reducing bone resorption.[11,12] In treatment-naïve postmenopausal women with osteoporosis, romosozumab significantly improved bone mass and reduced fracture risk compared to placebo or alendronate.[3,13,14] The benefits of the initial treatment with romosozumab for 12 months were maintained when patients were transitioned to either alendronate or denosumab.[3,13,15] Some patients who have previously received antiresorptive therapies might be candidates for romosozumab. To address a more common clinical scenario, we report here a post hoc, exploratory analysis of the effects of transitioning from denosumab to romosozumab in women with low bone mass not previously treated with romosozumab
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