Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

Figure 1

Skeleton regulates mineral and energy homeostasis. In mineral homeostasis, low level of circulating calcium stimulates the parathyroid gland to release PTH, which later upregulates blood calcium levels by stimulating osteoclastic bone resorption, renal calcium reabsorption, and renal production of Vitamin D to increase intestinal calcium absorption. Increased serum phosphate and Vitamin D stimulate FGF23 synthesis and releasing in bone, which subsequently inhibits PTH production from the parathyroid gland, inhibits Vitamin D production in the kidney, and promotes renal phosphate excretion. Leptin inhibits bone formation and the homeostatic function of the skeleton indirectly through SNS. However, SNS signalling also increases the production of OCN from bone, which feeds into the positive loop. OCN affects pancreatic β cells and increases insulin level, which has feedback effect on bone, driving further production of OCN. OCN also acts on fat to increase the production of adiponectin and upregulates insulin sensitivity. FGF23, fibroblast growth factor 23; PTH, parathyroid hormone; SNS, sympathetic nervous system.