Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study

Abstract

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 Nterminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. Conclusion: Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta‐analysis of randomized controlled trials (CDM‐J)

“…Eight studies 8,16–22 and one unpublished study (NCT02016716) analyzed the association between romosozumab and AEs during treatment versus placebo, alendronate, and teriparatide. Romosozumab 210 mg did not significantly change the risk of AEs during treatment versus placebo (RR = 0.98, 95% CI = 0.96–1.01, p = 0.75, n = 3983 romosozumab/ n = 3786 placebo, I 2 = 0%) or teriparatide (RR = 1.12, 95% CI = 0.94–1.32, n = 269 romosozumab/ n = 264 teriparatide, I 2 = 0%).…”

“…Six studies 8,16,18–21 and one unpublished study (NCT02016716) analyzed the association between romosozumab and serious AEs versus placebo, alendronate, and teriparatide. Romosozumab 210 mg did not significantly affect the risk of serious AEs versus placebo (RR = 0.92, 95% CI = 0.63–1.32, n = 3971 romosozumab/ n = 3774 placebo, I 2 = 14%), alendronate (RR = 0.78, 95% CI = 0.46–1.34, n = 269 romosozumab/ n = 268 teriparatide, I 2 = 0%), or teriparatide (RR = 0.93, 95% CI = 0.80–1.09, n = 2091 romosozumab/ n = 2065 alendronate, I 2 = 0%).…”

“…Twenty-four studies were excluded because they were sub-analyses, conference notes, canceled trials, post-hoc analyses, or studies conducted in male patients. After a comprehensive examination, eight studies 8,[16][17][18][19][20][21][22] and one unpublished trial (NCT02016716) were finally included in the study (Figure 1). The included studies compared romosozumab with placebo, alendronate, and teriparatide in…”

“…Lumbar spineThree studies16,19,21 and one unpublished study (NCT02016716) compared the efficacy of 6 or 12 months of treatment with romosozumab 210 mg or placebo, and romosozumab more effectively increased BMD (MD = 11.40, 95% CI = 8.06-14.74, n = 373 romosozumab/n = 238 alendronate, I 2 = 95%). Two studies 19,21 compared the efficacy of 12 months of treatment with romosozumab 140 mg or placebo, and romosozumab more strongly increased BMD (MD = 10.81, 95% CI = 7.68-13.95, n = 111 romosozumab/n = 113 placebo, I 2 = 89%).…”

Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates

“…Due to a coupling phenomenon, however, these agents concomitantly suppress bone formation, limiting their efficacy and possibly leading to increases in adverse events [5][6][7]. Although bone-forming agents, such as intermittent parathyroid hormone and romosozumab, have been suggested as alternatives, their anabolic activities last for only 1 or 2 years [8,9], which may not be sufficient to effectively prevent OF over a long period. Consequently, efforts are ongoing to identify novel therapeutic targets for osteoporosis and to maintain skeletal health in aging populations.…”