| Leptin is a hormone secreted by adipose tissue, widely involved in physiological processes such as energy balance, immune regulation, and bone metabolism. In recent years, leptin resistance, a hallmark of diseases like obesity and metabolic syndrome, has been increasingly recognized to be closely associated with the occurrence of osteoporosis. Leptin resistance leads to impaired leptin signaling, weakening its role in promoting bone formation while increasing bone resorption, thereby accelerating the progression of osteoporosis. This article reviews the mechanisms by which leptin resistance directly regulates the JAK-STAT and PI3K/Akt/mTOR signaling pathways, and indirectly affects the sympathetic nervous system, inflammation and immune responses, endoplasmic reticulum stress, mitochondrial function, autophagy, and interactions with other hormones. By exploring the multifaceted role of leptin resistance in bone metabolism imbalance, a deeper understanding of its specific effects in bone metabolism may offer new strategies for the prevention and treatment of osteoporosis, particularly in patients with obesity-related osteoporosis. |