Sequential treatment from bisphosphonate to denosumab improves lumbar spine bone mineral density in postmenopausal osteoporosis patients: A meta-analysis of randomized controlled trials

Abstract

Background: Bisphosphonates are effective in the treatment of postmenopausal osteoporosis. However, their prolonged use induces adverse events and may lead to a rapid decline in bone mineral density (BMD) after discontinuation. Denosumab, a human monoclonal antibody, is a widely used antiresorptive agent that is more effective than bisphosphonates in improving bone density. Whether sequential treatment with denosumab after bisphosphonate therapy can maintain or further increase BMD at all sites has not been conclusively demonstrated. Thus, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of this sequential therapy on BMD.

Methods: We searched the PubMed, Embase, and Cochrane Library databases from December 1, 1986, to May 2, 2024, for all RCTs that assessed the efficacy of sequential therapy of bisphosphonate transition to denosumab in postmenopausal women with osteoporosis. BMD changes at the lumbar spine, femoral neck, and total hip were used as outcomes. We assessed methodological quality, extracted relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions, applied random-effects models for meta-analyses, performed heterogeneity analyses, and assessed publication bias.

Results: A total of 3290 patients from 4 RCTs were included in the meta-analysis. Forest plot analysis showed that sequential treatment with bisphosphonate-denosumab was associated with higher lumbar spine BMD gain than continuous bisphosphonate treatment [mean difference (MD) = 5.50, 95% confidence interval (CI) = 5.26-5.75, I2 = 32.88%). No risk of bias was observed for the 4 trials, but there was an increase in femoral neck and total hip BMD. Moreover, analyses could not be performed because of high heterogeneity (femoral neck BMD: MD = 3.85, 95% CI = 2.84-4.85, I2 = 97.88%; total hip BMD: MD = 5.65, 95% CI = 4.28-7.02, I2 = 97.91%).

Conclusion: Sequential therapy that involves a transition from bisphosphonates to denosumab had a positive effect on lumbar spine bone density, and this type of therapy may be a potential treatment option for increasing lumbar spine bone density in postmenopausal women.