Meta-analysis of the Effectiveness of Romosozumab in the Treatment of Postmenopausal Osteoporosis

Introduction

Osteoporosis is a bone tissue disease characterized by changes in bone microarchitecture, reduced bone mineral density (BMD), and decreased bone strength, leading to an increased risk of fractures. A significant group of osteoporotic patients includes postmenopausal women, in whom the primary factor in bone mass loss is the decline in estrogen levels. 

Sclerostin is a molecule produced by osteocytes that inhibits osteoblastogenesis and bone formation by blocking Wnt signaling pathways. Targeting sclerostin inhibition is currently considered a potential treatment approach for osteoporosis. Romosozumab is a monoclonal antibody that binds to sclerostin, thus preventing its action. 

Literature Review and Analyzed Data

The cited meta-analysis evaluated the efficacy and safety of treating postmenopausal osteoporosis with romosozumab. The primary aim was to assess its impact on fracture incidence, BMD changes, fall frequency, occurrence of adverse events (AEs), and serious AEs compared to controls.

Only randomized controlled trials (RCTs) were included in the meta-analysis. Data from 10 appropriate RCTs out of 179 reviewed studies, involving 6137 patients in romosozumab groups and 5732 in control groups, were used. The search for suitable studies was conducted in the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. The methodological bias of the studies was assessed using the Cochrane Risk of Bias 2 Tool.

Results

Significant reduction in the incidence of vertebral fractures in the romosozumab group compared to the control group was observed over 12 months (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.40–0.65; p < 0.00001; high-quality evidence) and 24 months (OR 0.43; 95% CI 0.35–0.52; p < 0.00001; high-quality evidence), non-vertebral fractures over 24 months (OR 0.78; 95% CI 0.66–0.92; p = 0.003; high-quality evidence) and clinical fractures over 24 months (OR 0.70; 95% CI 0.60–0.82; p < 0.00001; high-quality evidence). 

The reduced risk of falls became statistically significant after 36 months of treatment with romosozumab (OR 0.85; 95% CI 0.77–0.95; p = 0.003; high-quality evidence); fall incidence among patients with romosozumab did not significantly differ from controls at 12 and 24 months. 

Significant improvement in lumbar spine BMD in the romosozumab group compared to the control group was demonstrated at 12 months (mean difference [MD] 12.66; 95% CI 12.66–12.67; p < 0.00001; high-quality evidence) and 24 months (MD 11.10; 95% CI 11.10–11.10; p < 0.00001; high-quality evidence), proximal femur BMD at 12 months (MD 5.69; 95% CI 5.68–5.69; p < 0.00001; moderate-quality evidence) and femoral neck BMD at 12 months (MD 5.18; 95% CI 5.18–5.19; p < 0.00001; moderate-quality evidence). 

The incidence of adverse events (relative risk [RR] 0.98; 95% CI 0.96–1.01; moderate-quality evidence) and serious AEs (RR 0.98; 95% CI 0.88–1.08; moderate-quality evidence) did not significantly differ between patients treated with romosozumab and the control group. 

Conclusion

The meta-analysis demonstrated high-quality evidence for the efficacy of romosozumab in treating osteoporosis in postmenopausal women in terms of reducing fracture incidence and improving lumbar spine BMD over 12 and 24 months and fall risk reduction after 36 months. BMD improvement in the proximal femur and femoral neck was supported by moderate-quality evidence. No significant differences were found compared to the control group in terms of adverse events, including serious ones, during romosozumab treatment. The authors of the meta-analysis recommend romosozumab as an effective and safe modality for treating postmenopausal osteoporosis based on these results.

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Source: Singh S., Dutta S., Khasbage S. et al. A systematic review and meta-analysis of efficacy and safety of romosozumab in postmenopausal osteoporosis. Osteoporos Int 2022; 33 (1): 1−12, doi: 10.1007/s00198-021-06095-y.