Association between gut microbiota, bone metabolism, and fracture risk in postmenopausal Japanese women

INTRODUCTION: We investigated the relationship between gut microbiota composition and osteoporosis/fracture risk in Japanese postmenopausal women using 16S rRNA gene sequencing, FRAX, bone mineral density, biochemical bone parameters, and a self-administered questionnaire. Variation in abundance of specific microbiota was found to be significantly associated with fracture risk and vitamin K levels. Gut microbiota data with respect to bone metabolism and fracture risk is limited. Vitamin K is produced by certain intestinal bacteria and has been reported to play a role in maintaining bone quality. PURPOSE: We investigated relationships among gut microbiota composition, bone metabolism, and fracture risk in postmenopausal Japanese women. METHODS: Bone mineral density (BMD) was evaluated in 38 postmenopausal women (mean age 62.9 years) using forearm dual-energy X-ray absorptiometry. We collected and analyzed serum bone turnover markers (vitamin K fraction and tartrate-resistant acid phosphatase 5b; TRACP-5b), gut microbiota profiling (16S rRNA gene sequencing), and self-administered questionnaire data, including fracture history and vitamin K intake. Vitamin K2, BMD, and TRACP-5b data were divided into high- and low-level groups using cutoff values of 0.06 ng/mL, 87.05%, and 420 mU/dL, respectively; the proportions of bacteria were analyzed. Fracture incidence and relative risk were investigated for each bacterium. RESULTS: The genus Bacteroides was predominant in the high vitamin K2 group (29.73% vs 21.58%, P = 0.022). Fracture incidence was significantly higher in the low Bacteroides group, with a 5.6-times higher risk ratio of fracture history. The family Rikenellaceae was more abundant in the low BMD group and more abundant in the high TRACP-5b group (2.15% vs 0.82%, P = 0.004; 2.38% vs 1.12%, P = 0.013, respectively). CONCLUSION: Bacteroides and Rikenellaceae may be involved in bone metabolism and fracture risk. Further investigations of the underlying microbiota-related pathways in bone metabolism may reveal treatment strategies, and facilitate the prevention of osteoporosis.