Targeting the gut–bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies

Osteoporosis (OP) is a systemic bone metabolic disorder characterized by impaired bone homeostasis and increased fracture susceptibility. With the rapid aging of the global population, the number of fractures related to osteoporosis continues to increase, along with persistently high rates of disability and mortality, thereby imposing a huge and constantly growing burden on the healthcare system. Emerging evidence indicates that probiotics, as key regulators of host metabolic and immune networks, play critical roles in the pathogenesis, progression, and therapeutic modulation of OP. Through a bidirectional regulatory network known as the gut-bone axis, probiotics influence the dynamic balance between bone formation and bone resorption via multiple interconnected mechanisms, including immune modulation, microbial metabolite production, intestinal barrier integrity, and endocrine signaling. Recent animal and clinical studies further demonstrate that targeted modulation of the gut microbiota to restore gut-bone axis homeostasis can significantly improve bone mineral density and related skeletal parameters, highlighting the translational potential of probiotic-based interventions. This review systematically summarizes the molecular mechanisms by which probiotics regulate bone metabolism and places particular emphasis on emerging microbiota-based mechanisms and therapeutic strategies, with a specific focus on probiotics, aiming to provide a theoretical framework and future translational directions for the development of innovative microbiota-based treatments for OP.