Gut Microbiota and SCFA Changes After Alendronate-Calcitriol Therapy in Postmenopausal Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMO) is driven primarily by estrogen deficiency, and gut microbiota-derived metabolites may participate in bone remodeling. The intestinal effects of conventional anti-osteoporosis therapy remain unclear. We investigated gut microbial and short-chain fatty acid (SCFA) changes associated with alendronate-calcitriol therapy in PMO. METHODS: Forty-one postmenopausal women were enrolled, including 21 healthy controls and 20 patients with PMO. PMO patients received oral alendronate plus calcitriol for six months, with paired fecal samples collected before and after treatment. Shotgun metagenomic sequencing was used to assess microbial taxonomy, KEGG pathways, and CAZy profiles. Fecal SCFAs were quantified by gas chromatography-mass spectrometry. RESULTS: After treatment, lumbar spine BMD T-score improved from -2.98 to -2.65, and femoral neck BMD T-score increased from -2.40 to -2.12, and all measured bone turnover markers (BALP, TRACP-5b, PINP and osteocalcin) decreased significantly (P < 0.05). Global microbial diversity did not differ significantly among groups, but treatment was accompanied by shifts in specific taxa. Roseburia, Megamonas, Dialister, and unclassified Lactobacillaceae increased, whereas Enterobacter, Salmonella, Raoultella, Serratia, and Rahnella decreased. Functional profiles showed treatment-associated shifts in propanoate metabolism, pyruvate metabolism, the TCA cycle, and selected carbohydrate-active enzyme patterns. Overall fecal SCFA composition remained relatively stable; however, propionic acid concentration increased significantly after treatment (FDR-adjusted P = 0.021). Correlation analyses linked selected commensal taxa and SCFAs with BMD and bone turnover markers. CONCLUSION: Alendronate-calcitriol therapy was associated with improved bone metabolism and treatment-associated shifts in gut microbial composition, microbial functional potential, and propionate-related SCFA profiles. These findings provide preliminary evidence for microecological changes accompanying conventional PMO therapy.