Research Progress on Mechanisms of Milk-Derived Functional Components in Regulating Bone Health and the Gut-Bone Axis.

Osteoporosis affects over 200 million people worldwide, with postmenopausal women at the highest risk. The treatment benefits of currently available drugs are constrained by safety concerns, and they lack bidirectional regulation of bone metabolism, driving growing interest in safe dietary interventions. Milk is rich in functional components, including minerals (calcium, phosphorus), casein phosphopeptide (CPP), lactoferrin (LF), osteopontin (OPN), and milk fat globule membrane (MFGM), that promote mineral absorption, regulate bone cell activity, and support intestinal health. This review examines their dual mechanisms in bone health regulation. Directly, LF activates Wnt/MAPK pathways to enhance osteogenesis and inhibit osteoclast activity, OPN modulates mineralization, and CPP synergizes with calcium and phosphorus to support bone formation. Indirectly, these components modulate gut microbiota via the gut-bone axis, raising short-chain fatty acids, lowering intestinal pH to boost calcium absorption, repairing the intestinal barrier, and reducing systemic inflammation. Remaining challenges lie in extraction, purification, and product development. Looking forward, the field must move from cell and animal-level evidence to human clinical validation and establish robust steady-state delivery of these bioactives. Successful translation along these lines is essential to turn milk-derived components into effective, evidence-based functional foods for bone health.