Gut Microbiota-Modulating Interventions for Osteoporosis: Bone Health Outcomes and Gut-Bone Pathways—A Systematic Review

Background: Osteoporosis is characterized by reduced bone mass and deteriorating bone microarchitecture, increasing fracture risk. Emerging evidence suggests that the gut microbiota influences skeletal health through microbial metabolites, intestinal barrier function, immune regulation, and bone remodeling. However, the therapeutic benefits of microbiota modulation remain uncertain. Objective: This review evaluated the association between gut microbiota-modulating interventions and bone outcomes in osteoporosis and explored the underlying biological mechanisms. Methods: Following PRISMA 2020 guidelines, PubMed and Google Scholar were searched in June 2026 for original studies published between 2021 and 2026. Eligible studies investigated microbiota-modulating interventions in osteoporosis or related low bone mineral density conditions. Methodological quality was assessed using Cochrane RoB 2 and SYRCLE tools. Findings were synthesized narratively due to methodological heterogeneity. Results: Of 346 identified records, six studies met the inclusion criteria, comprising four clinical studies and two animal experiments. Interventions included probiotics, synbiotics, bioactive compounds, and combination treatments. Improvements were observed in selected outcomes, including bone mineral density, microarchitecture, bone formation, and strength, with more consistent findings in animal models. Proposed mechanisms involved microbial composition, short-chain fatty acid production, intestinal barrier integrity, and immune regulation. Conclusion: Gut microbiota-modulating interventions show potential as complementary approaches to osteoporosis management. However, limited and heterogeneous evidence prevents definitive clinical recommendations. Larger, well-controlled clinical trials are needed to establish efficacy and clarify relevant gut–bone mechanisms in humans.