β-Blockers and bone health

Abstract

Bone metabolism is controlled by endocrine, paracrine, and inflammatory signals that continuously operate in health and disease. While these signals are critical for skeletal adaptation during development, longitudinal growth, and repair, disturbances such as sex hormone deficiency or chronic inflammation have unambiguously been linked to bone loss and skeletal fragility across species. In the current issue of the JCI, Khosla et al. evaluated the role of sympathetic outflow and present evidence to support the idea that the sympathetic nervous system regulates bone metabolism in humans, primarily via the β1-adrenergic receptor.

Figure 1. The major catecholamines epinephrine and norepinephrine are produced in the adrenal medulla and in postganglionic sympathetic fibers projecting from paraganglia.

Activated sympathetic outflow with elevated production occurs in pheochromocytoma and more subtly in the postmenopausal phase, at an older age, or in conditions of chronic mild stress. Activation of the widely expressed β-AR transmits its signal to the second messenger cyclic adenosine monophosphate (cAMP). In bone, sympathetic activation stimulates osteoclastic bone resorption and suppresses osteoblastic bone formation, thus contributing to bone loss. With the use of the β₁-AR–selective blockers nebivolol and atenolol, mainly bone resorption is reduced, and bone loss is prevented.