Potential roles of food-derived bioactive peptides in osteoporosis through the gut-bone axis

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, microarchitectural deterioration, and increased fracture risk. However, long-term use of current pharmacological therapies is often associated with adverse effects, underscoring the urgent need for safer and more sustainable intervention strategies. Food-derived bioactive peptides have attracted increasing attention because of their potential anti-osteoporotic effects and natural origin. Upon intestinal entry, these peptides may modulate the gut microbiota and its metabolites, improve immune-inflammatory responses, and maintain intestinal homeostasis, thereby influencing bone homeostasis. The gut-bone axis, as a key bidirectional regulatory network connecting the gut microenvironment and bone metabolism, provides a new research perspective for understanding the potential link between food-derived bioactive peptides and bone health. This review systematically summarizes the potential mechanisms by which food-derived bioactive peptides exert bone-protective effects through regulation of the gut-bone axis. Furthermore, we discuss current research progress, remaining challenges, and future directions, with the aim of providing a theoretical foundation for the development of peptide-based intervention strategies against osteoporosis. Given that the current evidence is mainly derived from in vitro and animal studies, the actual effects of food-derived bioactive peptides on osteoporosis still need to be further validated through clinical studies.