Denosumab for Primary Osteoporosis and Its Impact on Sarcopenia in the Chinese Population: Insights from Clinical...

With the rapid aging of China's population, osteoporosis and sarcopenia have become major public health challenges. Denosumab, a first-line therapy for osteoporosis, may also improve muscle health, a possibility warranting further investigation.

This study evaluated the efficacy of denosumab in treating primary osteoporosis in the Chinese population and explored its potential effects on sarcopenia. A Mendelian randomization (MR) analysis was additionally performed to investigate the causal role of the RANKL pathway in sarcopenia.

This study included two components. In the clinical study, 45 patients with primary osteoporosis received denosumab, of whom 40 completed a 6-month follow-up and 15 completed a 1-year follow-up. Outcomes included bone turnover markers, bone mineral density, muscle strength, and physical performance measures. In the genetic study, two-sample MR was conducted using genome-wide association study (GWAS) summary statistics to assess the causal association between RANKL gene variants and sarcopenia-related traits, including appendicular lean mass and grip strength.

Denosumab significantly reduced bone turnover markers and improved muscle function after 6 months, with further gains in bone mineral density and muscle strength observed at 1 year (all P < 0.05). Muscle mass showed upward but non-significant trends. MR analysis revealed a significant negative association between RANKL expression and both appendicular lean mass and grip strength, with no evidence of heterogeneity or pleiotropy.

Denosumab effectively treats osteoporosis and improves muscle function in Chinese patients. Genetic evidence supports a causal role of the RANKL pathway in sarcopenia, indicating that RANKL overexpression may contribute to its development. By integrating clinical and genetic evidence, our findings suggest that denosumab may represent a promising therapeutic option for patients with concurrent osteoporosis and sarcopenia.