Adrenergic control of bone remodeling and its implications for the treatment of osteoporosis.

Abstract

Evidence that leptin regulates bone turnover in part through a central nervous system (CNS)/beta-adrenergic system relay has driven attention towards the potential therapeutic benefits of beta-adrenergic blockade to improve bone mass and strength. beta2- adrenergic receptor-mediated signaling in osteoblasts inhibits bone formation and triggers RANKL-mediated osteoclastogenesis and bone resorption. Mouse models of adrenergic-deficiency, particularly the mouse lacking the beta2-adrenergic receptor, have increased bone mass, more specifically increased trabecular bone volume. In turn, beta-blockers, such as propranolol, were reported to inhibit ovariectomy-induced bone loss. In contrast, a number of experiments in mice and rats suggest that inhibition of beta-adrenergic receptor-mediated signaling does not improve, and could actually be detrimental, for bone mass and microstructure. In humans, epidemiological observations suggested that users of beta-blockers have higher bone mineral density (BMD) and/or a reduced risk of fractures, yet not all studies were concordant. Here we review the evidence for a role of the adrenergic system in the regulation of bone metabolism in vitro and in vivo and provide some new evidence for a dual role of beta-adrenergic receptors 1 and 2 on bone turnover. Furthermore, we will examine the similarities and disparities that may exist in the effects of beta-adrenergic and PTH stimulation on bone metabolism.