BONE REMODELING: CENTRAL NERVOUS SYSTEM CONTROL AND ROL OF LEPTIN

The skeleton is constantly being remodeled by the coordinated action of osteoblasts and osteoclasts. A delicate equilibrium between bone formation and resorption is needed to maintain mineral homeostasis and biomechanical integrity. The activity of bone cells is regulated by systemic hormones and also by local factors, produced by these cells. Such factors, cytokines and prostaglandins, are in turn partially regulated by systemic hormones. It has recently been suggested that bone remodeling, like other homeostatic functions, is under the control of the central nervous system (CNS) through efferent pathways. Bone cells have receptors for several neuropeptides that are thought to mediate control by the CNS. Several findings indicate that a hormone regulating appetite, energy consumption, and reproduction is also implicated in the regulation of bone remodeling. This could represent a link between calorigenesis and mineral metabolism. Leptin is a hormone produced predominantly, but not exclusively, by white fat; it is transported bound to specific receptors, goes through the blood-brain barrier and binds to hypothalamic receptors. One of the consequences is the activation of the sympathetic nervous system, which could be involved in the control of bone remodeling. Leptin, acting via beta2adrenergic receptors in osteoblasts, is antiosteogenic. At the same time, and acting through the same receptors in the osteoclasts, it is osteoclastogenic. However, the central regulating mechanism is different. On the other hand, osteoblasts control energy balance through a negative feedback loop. The "hormone" implicated in this process could well be decarboxylated osteocalcin.