title: The effects of beta-2 adrenergic agonist and antagonist on human bone metabolism: a randomized controlled trial.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dept. of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: a.g.veldhuis-vlug@amc.uva.nl.
authors.forename: A G
authors.initials: AG
authors.lastname: Veldhuis-Vlug
authors.affiliation: Dept. of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: m.w.tanck@amc.uva.nl.
authors.forename: M W
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Dept. of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: e.j.limonard@amc.uva.nl.
authors.forename: E J
authors.initials: EJ
authors.lastname: Limonard
authors.affiliation: Dept. of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: e.endert@amc.uva.nl.
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.affiliation: Dept. of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: a.heijboer@vumc.nl.
authors.forename: A C
authors.initials: AC
authors.lastname: Heijboer
authors.affiliation: Dept. of Internal Medicine, Endocrine Section, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: p.lips@vumc.nl.
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.affiliation: Dept. of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: e.fliers@amc.uva.nl.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Dept. of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: p.h.bisschop@amc.uva.nl.
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin
keywords: Beta-adrenergic agonist; Beta-adrenergic antagonist; Bone turnover; Randomized controlled trial; Sympathetic nervous system