title: Clonidine increases bone resorption in humans.
abstract: CONCLUSIONS
  Inhibition of sympathetic signaling to bone reduces bone resorption in rodents. In contrast, we show that pharmacological reduction of the sympathetic tone increases bone resorption in humans in vivo. This effect does not appear to be mediated via a direct pharmacological effect on the osteoclast.
  
  
  BACKGROUND
  Inhibition of sympathetic signaling to bone reduces bone resorption in rodents. It is uncertain whether a similar role for the sympathetic nervous system exists in humans. The sympathetic tone can be reduced by clonidine, which acts via alpha-2-adrenergic receptors in the brainstem. Our objective was to determine the effect of clonidine on bone turnover in humans.
  
  
  METHODS
  The acute effect of a single oral dose of 0.3 mg clonidine on serum bone turnover markers (C-terminal cross-linking telopeptides of collagen type I (CTx), a marker for bone resorption, and procollagen type 1 N propeptide (P1NP), a marker for bone formation) was determined in a randomized crossover design in 12 healthy volunteers, aged 18-70 years. In addition, we assessed the effect of clonidine on the number of tartrate-resistant acid phosphatase-positive multinucleated cells (TRAcP(+) MNCs) and bone resorption.
  
  
  RESULTS
  CTx concentrations increased after clonidine treatment compared to the control condition (p = 0.035). P1NP concentrations were not affected by clonidine (p = 0.520). In vitro, clonidine had no effect on the number of TRAcP(+) MNCs (p = 0.513) or on bone resorption (p = 0.996).
  
  
  CONCLUSIONS
  We demonstrated that clonidine increases bone resorption in humans in vivo. This effect does not appear to be mediated via a direct effect on the osteoclast.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Limonard
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, MOVE Research Institute, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Schoenmaker
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, MOVE Research Institute, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: de Vries
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Heijboer
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, MOVE Research Institute, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Everts
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, Netherlands. p.h.bisschop@amc.uva.nl.
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced*; D002478:Cells, Cultured; D003000:Clonidine / Q000009:adverse effects* / Q000494:pharmacology; D024042:Collagen Type I / Q000097:blood; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; 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; D000071681:Tartrate-Resistant Acid Phosphatase; D003000:Clonidine
keywords: Alpha-2-adrenergic receptor; Bone turnover; Osteoclast; Sympathetic nervous system