Denosumab ameliorates muscle indices in Chinese osteoporosis patients through clinical and bioinformatic evidence of RANKL in sarcopenia

This study investigated the effects of denosumab on muscle parameters in Chinese patients with primary osteoporosis and explored potential mechanisms through bioinformatic analyses. In a clinical trial involving 103 patients, 12 months of denosumab treatment significantly improved bone mineral density, grip strength, 6-m walk gait speed, 5 times sit-up time, and Timed Up and Go (TUG) test compared with baseline and calcium plus vitamin D therapy (<i>p</i> < 0.05). Bioinformatic analysis of GEO datasets (GSE111006, GSE111010, and GSE111016) showed that RANKL expression was upregulated in sarcopenia (<i>p</i> = 0.007) and enriched in PI3K-Akt, MAPK, and cytoskeletal signaling pathways related to muscle growth and inflammation. These findings indicate that denosumab not only enhances bone mass but also improves muscle strength and function, potentially through RANKL inhibition and modulation of myogenic and inflammatory pathways, supporting its therapeutic potential for patients with coexisting osteoporosis and sarcopenia.