The gut-bone-inflammation axis: intestinal barrier disruption as a central driver of osteoporosis

Osteoporosis is a systemic skeletal disorder traditionally attributed to imbalances in bone metabolism. Increasing evidence suggests that the intestinal environment and chronic inflammation play important roles in itspathogenesis. The gut-bone-inflammation axis provides a novel perspective for understanding the interactions among intestinal barrier function, immune regulation, and bone homeostasis. This review aims to summarize current evidence regarding the role of intestinal barrier disruption in osteoporosis and to discuss its contribution within the framework of the gut-bone-inflammation axis. Relevant experimental and clinical studies from the existing literature were reviewed and synthesized, with a focus on intestinal barrier integrity, gut microbiota dysbiosis, inflammatory mediators, immune activation, and bone metabolism. Disruption of the intestinal barrier increases intestinal permeability, facilitating the translocation of microbial products and pro-inflammatory mediators into the systemic circulation. This process promotes chronic low-grade inflammation, enhances osteoclast differentiation and activity, suppresses osteoblast function, and disrupts the balance of bone remodeling. Gut microbiota imbalance, immune activation, and sustained inflammatory signaling collectively contribute to bone loss and structural deterioration in osteoporosis. Intestinal barrier dysfunction plays a pivotal role in osteoporosis through modulation of systemic inflammation and bone metabolism. Strategies aimed at preserving intestinal barrier integrity and regulating the gut microbiota may offer promising preventive and therapeutic approaches for the management of osteoporosis.