Causal associations between osteosarcopenia-related traits and degenerative spinal disorders: a bidirectional Mendelian randomization study

Purpose: Osteosarcopenia, characterized by the concurrent deterioration of bone and muscle, is increasingly recognized as a major geriatric syndrome. However, its causal role in degenerative spinal disorders remains unclear owing to confounding and reverse causation in observational studies.Methods: Two-sample Mendelian randomization (MR) was performed using appendicular lean mass (ALM), hand grip strength (HGS), walking pace (WP), and total bone mineral density (BMD) as variables. The outcomes included intervertebral disc disorder (IVDD), spinal stenosis, and spondylosis. Bidirectional MR analysis was also conducted. Genome-wide association study data were obtained from the UK Biobank, Million Veteran Program and Genetic Investigation of Anthropometric Traits (GIANT) consortium. Inverse-variance weighted was the main method for evaluating the causal relationship. Linkage disequilibrium score regression (LDSC) was used to assess genetic correlations. Multivariable MR incorporating body mass index was performed to identify the direct and indirect pathways.Results: LDSC revealed significant genetic correlations between ALM and total BMD and degenerative spinal disorders, and WP showed consistent negative genetic correlations across outcomes. In univariable MR, genetically predicted higher ALM was associated with increased risks of IVDD, spinal stenosis, and spondylosis, whereas faster WP and higher total BMD were protective. HGS showed no robust association in the primary MR analyses, although a modest protective signal for spondylosis appeared only after outlier correction. Reverse-direction MR provided limited evidence of causality.Conclusion: Osteosarcopenia-related traits exhibit heterogeneous causal relationships with degenerative spinal disorders. Muscle mass (ALM) was positively associated with the risk of spinal disorders, whereas mobility (WP) and bone density (BMD) were protective. Body size-related pathways likely contribute to these relationships, and method-dependent findings—particularly for HGS and reverse-direction analyses—should be interpreted cautiously.