Gut microbiota dysbiosis and osteoporosis: pathogenesis and novel intervention strategies

Osteoporosis represents a major global public health challenge, with current pharmacological treatment often limited by substantial side effects. Recent research identifies the gut-bone axis as a key regulatory pathway linking gut microbiota to bone metabolic homeostasis. This review synthesizes findings from PubMed, Web of Science, and Scopus (up to March 2026) to elucidate how gut microbiota dysbiosis drives osteoporosis pathogenesis through interconnected mechanisms: aberrant immune modulation, altered microbial metabolites, impaired nutrient absorption, endocrine disruption, and systemic inflammation stemming from intestinal barrier failure. Consequently, these pathways disrupt the delicate balance of bone remodeling. Based on these insights, we outline novel microbiota-targeted therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, natural bioactive compounds, traditional Chinese medicine, and nanomaterials. These interventions aim to prevent and manage osteoporosis by reshaping the intestinal microecology via multi-target modulation. Future endeavors should prioritize in-depth mechanistic exploration, personalized precision interventions, and enhanced clinical translation to integrate these strategies into comprehensive osteoporosis care frameworks.