The effects of beta-2 adrenergic agonist and antagonist on human bone metabolism: a randomized controlled trial

Abstract

Purpose: Genetic knockout or pharmacological inhibition of the beta-2 adrenergic receptor (B2AR) increased bone mass, whereas stimulation decreased bone mass in rodents. In humans, observational studies support sympathetic nervous system regulation of bone metabolism, but intervention studies are lacking. We aimed to determine the effects of a selective beta-2 adrenergic agonist and non-selective antagonist on human bone metabolism.

Methods: 32 healthy postmenopausal women were included in a randomized controlled trial conducted in the Academic Medical Center Amsterdam. Participants were randomized to receive treatment with 17-β estradiol 2mg/day; 17-β estradiol 2mg/day and terbutaline 5mg/day (selective B2AR agonist); propranolol 80mg/day (non-selective B-AR antagonist); or no treatment during 12weeks. Main outcome measure was the change in serum concentrations of procollagen type I N propeptide (P1NP) and C-terminal crosslinking telopeptides of collagen type I (CTx) as markers of bone formation and resorption after 12weeks compared between the treatment groups. Data were analyzed with mixed model analysis.

Results: 17-β estradiol decreased bone turnover compared to control (P1NP p<0.001, CTx p=0.003), but terbutaline combined with 17-β estradiol failed to increase bone turnover compared to 17-β estradiol alone (P1NP p=0.135, CTx p=0.406). Propranolol did not affect bone turnover compared to control (P1NP p=0.709, CTx p=0.981).

Conclusion: Selective beta-2 adrenergic agonists and non-selective beta-antagonists do not affect human bone turnover although we cannot exclude small changes below the detection limit of this study.

Keywords: Beta-adrenergic agonist; Beta-adrenergic antagonist; Bone turnover; Randomized controlled trial; Sympathetic nervous system.