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DOI: https://doi.org/10.4235/agmr.22.0139    [Accepted]
Published online January 11, 2023.
Denosumab's Therapeutic Effect for Future Osteosarcopenia Therapy : A Systematic Review and Meta-Analysis
I Gusti Putu Suka Aryana1  , Sandra Surya Rini2, Siti Setiati3
1Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Bali, Indonesia
2Department of Internal Medicine, North Lombok Regional Hospital, West Nusa Tenggara, Indonesia
3Clinical Epidemiology and Evidence-Based Medicine Unit, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Correspondence:  I Gusti Putu Suka Aryana,
Email: ptsuka_aryana@unud.ac.id
Received: 16 November 2022   • Revised: 28 December 2022   • Accepted: 5 January 2023
Abstract
Background
Osteosarcopenia, a combination of osteopenia/osteoporosis and sarcopenia, is a common condition among older adults. While numerous studies and meta-analyses have been conducted on the treatment of osteoporosis, the pharmacological treatment of osteosarcopenia still lacks evidence. Denosumab, a human monoclonal antibody, has shown encouraging results for the treatment of osteosarcopenia. Our systematic review and meta-analysis aimed to investigate the potential dual role of denosumab as an anti-resorptive agent and for other beneficial muscle-related effects in patients with osteosarcopenia, and to evaluate whether denosumab can be a treatment of choice compared to bisphosphonate.
Methods
Relevant literature was collated from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Google Scholar databases. The primary outcome was denosumab’s effect on lumbar spine bone mineral density (LS BMD), handgrip strength, and gait speed change. The secondary outcome was the effect of denosumab on appendicular lean mass (ALM). The outcomes were presented as mean difference (MD). A random effects model was used in the analysis to represent the population. The risk of bias was assessed using funnel plots.
Results
Out of the 3,074 studies found, four full-text studies met the inclusion criteria, including 264 and 244 participants in the intervention and control groups, respectively. Regarding a primary outcome, our meta-analysis showed that denosumab had no significant effect on LS BMD and gait speed changes compared to placebo/other agents—MD=0.37, 95% confidence interval (CI), -0.35 to 0.79; p=0.09 and MD=0.11; 95% CI, -0.18 to 0.40; p=0.46, respectively. Denosumab had a significant effect on handgrip strength change compared to standard agents—MD=5.16; 95% CI, 1.38 to 18.94; p=0.007, based on the random effects model.
Conclusions
Denosumab was better than bisphosphonate and placebo in improving muscle strength (handgrip strength). Therefore, denosumab may be favored in individuals with osteosarcopenia to improve muscular performance and reduce fall risk.
Key Words: Denosumab, Osteosarcopenia, Osteoporosis, Sarcopenia


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