Glucose metabolism in osteoporosis: A potential therapeutic target (Review)
TL;DR
It is demonstrated that abnormal glucose metabolism is a key pathogenic mechanism in osteoporosis and that targeting insulin signaling may represent a fundamental strategy for correcting glucose metabolic abnormalities across diverse etiologies.
Abstract
Osteoporosis is a systemic skeletal disease characterized by progressive bone loss and an increased risk of fracture, and it represents a major public health challenge worldwide. Osteoporosis has multiple pathogenic determinants, including age, endocrine disorders and medication. Current therapeutic approaches primarily aim to promote osteogenesis directly or inhibit osteoclast activity; however, these strategies may limit therapeutic efficacy and increase the risk of adverse effects. The present review provided an integrated perspective on the pathogenesis of osteoporosis from the standpoint of glucose metabolism. Glucose oxidation generates ATP and metabolic intermediates that are key to bone homeostasis. During early differentiation, mesenchymal stem cells rely predominantly on glycolysis during commitment toward pre-osteoblasts, whereas maturation into functional osteoblasts depends more notably on oxidative phosphorylation. The fusion and differentiation of osteoclasts require robust mitochondrial oxidation. Lactate derived from anaerobic metabolism has a dual role in bone metabolism. High-risk populations for osteoporosis include postmenopausal women, patients with type 2 diabetes mellitus and individuals with obesity. Estrogen exerts anti-inflammatory and antioxidant effects through receptor activation. Excessive production of advanced glycation end-products disrupts the bone matrix, whereas hyperlipidemia promotes inflammatory factor-induced bone resorption. These pathological changes disrupt the insulin receptor substrate/PI3K/AKT signaling pathway, compromise glucose transporter-mediated cellular glucose uptake and thus, contribute to relative insulin resistance and insufficiency compared with physiological states. In conclusion, the present review demonstrated that abnormal glucose metabolism is a key pathogenic mechanism in osteoporosis and that targeting insulin signaling may represent a fundamental strategy for correcting glucose metabolic abnormalities across diverse etiologies.