Unveiling GDF-15: a new frontier in combating diabetic osteoporosis

Diabetic osteoporosis (DOP) is a diabetes mellitus (DM) complication, defined by diminished bone density and a significantly increased fracture risk due to disorders in bone metabolism, making it a key clinical concern. Growth differentiation factor-15 (GDF-15), a transforming growth factor-β superfamily member, has broad target specificity and exerts diverse biological effects through multiple signaling pathways, drawing attention to its role in metabolic diseases. GDF-15 has been implicated in the regulation of osteoblast- and osteoclast-related processes. It is abnormally expressed in DOP patients and may be correlated with disease progression, potentially mediated by insulin resistance, hyperglycemic toxicity, ferroptosis, and inflammatory responses. Although some biological functions of GDF-15 have been elucidated, its specific pathways in this disease and clinical application value warrant further studies. This review summarizes recent advances in basic and clinical research, elucidates the pathophysiological mechanisms behind GDF-15 in DOP, and provides theoretical support and research directions for GDF-15-based targeted therapeutic strategies.