Gut Microbiome Signatures Associated with Osteoporotic Vertebral Compression Fracture

Osteoporotic vertebral compression fracture (OVCF) is a clinically important condition associated with pain, disability, and impaired quality of life. Although osteoporosis is commonly diagnosed based on bone mineral density (BMD), fracture occurrence cannot be fully explained by BMD alone, suggesting that additional systemic factors may contribute to fracture susceptibility. The gut microbiome has recently emerged as a potential regulator of bone metabolism; however, its association with OVCF remains insufficiently characterized. In this study, fecal microbiome profiling using 16S rRNA gene sequencing was performed in 29 healthy controls, 11 patients with osteoporosis, and 25 patients with OVCF. Compared with the healthy control and osteoporosis groups, the OVCF group exhibited more distinct gut microbial compositional differences and reduced microbial diversity. Differential abundance analyses identified an increased relative abundance of Alistipes in the OVCF group and a higher relative abundance of Prevotella in healthy controls, with these taxa showing negative and positive correlations with BMD, respectively. Functional profiling further suggested differences in microbial metabolic pathways associated with OVCF, including increased mucin-derived carbohydrate degradation and reduced polyamine metabolism pathways. Consistently, fecal short-chain fatty acid concentrations were significantly lower in the OVCF group, accompanied by a reduced abundance of short-chain fatty acid-producing taxa and alterations in related microbial pathways. Overall, these findings suggest that gut microbial and metabolic alterations are associated with OVCF status rather than osteoporosis alone. The identified microbial signatures provide preliminary evidence of OVCF-associated microbial alterations; however, further validation in independent cohorts and longitudinal studies is required before their diagnostic or predictive value can be established.