Immunosenescence-driven bone marrow immune niche destabilization in osteoporosis: microenvironmental targets and natural product-mediated reprogramming

Osteoporosis is a heterogeneous skeletal disorder arising from diverse age-related, endocrine, metabolic, mechanical, and pharmacological factors. In age-related, postmenopausal, and selected metabolism-associated forms of osteoporosis, immunosenescence may contribute to dysfunction in the bone marrow immune niche, thereby amplifying bone resorption and regenerative decline. This review examines osteoporosis through the complementary perspective of the bone marrow immune niche and summarizes the core mechanisms by which immunosenescence contributes to destabilization of the bone marrow immune niche in osteoporosis. On this basis, we further discuss the molecular basis and regulatory potential of natural products in mediating bone marrow-related immune microenvironmental reprogramming. Emerging technologies, including single-cell omics, spatial omics, organoid models, and humanized research platforms, are also integrated to propose novel strategies for the precision prevention and treatment of osteoporosis. Overall, this review incorporates immune microenvironmental regulation into the conventional framework of bone metabolic dysfunction and provides a systematic theoretical basis for mechanistic elucidation, precision delivery, and clinical translation of natural products in prevention and treatment of osteoporosis.