Drug-induced osteoporosis mechanisms and gut microbiota links remain largely unresolved for most medication classes

Drug-induced osteoporosis is considered secondary osteoporosis caused by pharmacological drugs that can alter the diversity and function of the gut microbiota (GM), which in turn may be associated with the development or exacerbation of osteoporosis. This review uncovers the relationship between drug-induced osteoporosis and GM based on preclinical and clinical studies. In this context, we focused on secondary osteoporosis induced by glucocorticoids, aromatase inhibitors, proton pump inhibitors, antiretroviral drugs, antiepileptic drugs, antipsychotics, antidepressants, and subsequent alterations in the GM. Different pharmacological drugs can induce secondary osteoporosis through multiple mechanisms, and some of them exert similar mechanisms of their harmful effect on bone health, including decreased osteoblastogenesis, increased osteoclastogenesis, disturbances in calcium and vitamin D metabolism, alterations in hormone and cytokine levels. In addition, diverse drugs can significantly reshape gut microbial communities, often in a drug- and context-specific manner. However, the mechanisms linking individual drugs, GM, and bone health are still largely unresolved. There is little or no direct evidence that drug-induced GM alterations mediate changes in bone turnover, bone mineral density (BMD), or fracture risk for most of the drug classes mentioned. Observational and interventional clinical studies in this area are necessary to provide conclusive evidence of the association between drug-induced osteoporosis and GM. Therapeutic approaches that have shown promise in the treatment of medication-induced osteoporosis include pharmacological interventions, adequate calcium and vitamin D intake, weight-bearing exercise, and preventive monitoring of BMD. Probiotic and prebiotic supplementation may be a future option if supported by compelling clinical evidence.