Clinical evidence linking osteoporosis and the gut microbiome in postmenopausal females: A systematic review

Background

Recent studies have highlighted the intricate relationship between gut microbiome (GM) and osteoporosis (OP), particularly in postmenopausal females. However, the precise mechanisms underlying this association remain unclear.

Materials and methods

This retrospective review and meta-analysis aimed to elucidate the role of GM in postmenopausal OP (PMO) by synthesizing clinical findings from recent literature. A systematic search of four databases (PubMed, Google Scholar, Cochrane Library, and Web of Science) identified 16 relevant clinical studies published between January 2000 and July 2025.

Results

A total of 1520 postmenopausal females (mean age: 59.25 ± 6.63 years) were included, comprising 656 patients with PMO and 864 healthy controls (HC). A meta-analysis of gut microbial α diversity revealed a significant reduction (p = 0.04) in the abundance-based coverage estimator (ACE) index in patients with PMO, indicating a loss of microbial richness. At the same time, β-diversity findings were inconsistent across studies. Taxonomic analysis confirmed differences between patients and HC at the phylum and genus levels. PMO is characterized by a significant increase in primary bile acids and a reduction in tryptophan and daidzein metabolism at the metabolic level. Additionally, Patients with PMO exhibited markedly lower serum estradiol levels, higher levels of lipopolysaccharide and tumor necrosis factor-α, a higher proportion of Th17 cells, and a lower Treg cell population, indicating a pro-inflammatory state.

Conclusion

Overall, this review provides a comprehensive synthesis of current clinical evidence on the role of GM in PMO, emphasizing its potential impact on bone metabolism. Given these findings, targeting the composition of gut microbiota and its metabolites may offer a promising therapeutic strategy for mitigating OP in postmenopausal females.