Adrenergic control of bone remodeling and its implications for the treatment of osteoporosis.
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.
Bonnet
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N
Division of Bone Diseases, Department of Rehabilitation and Geriatrics, WHO Collaborating Center for Osteoporosis Prevention, Geneva University Hospital, Geneva, Switzerland.
Pierroz
D D
DD
Ferrari
S L
SL
D018663:Adrenergic Agents / Q000627:therapeutic use*; D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D018663:Adrenergic Agents; D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D010281:Parathyroid Hormone; D011941:Receptors, Adrenergic; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2