title: Modifications of histamine receptor signaling affect bone mechanical properties in rats.
abstract: Histamine receptors are expressed on bone cells and histamine may be involved in regulation of bone metabolism. The aim of the present study was to investigate the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2) receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1) receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day, po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day, po), were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were compared with appropriate controls. Serum levels of bone turnover markers, bone mineralization and mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck were studied. In rats with normal estrogen level, administration of loratadine slightly favorably affected mechanical properties of compact bone, significantly increasing the strength of the femoral neck (p < 0.05), and tending to increase the strength of the femoral diaphysis. Ranitidine did not significantly affect the investigated parameters, and betahistine decreased the strength of the tibial metaphysis (cancellous bone, p < 0.01). There were no significant effects of the drugs on serum bone turnover markers. In estrogen-deficient rats, the drugs did not significantly affect the investigated skeletal parameters. In conclusion, the effects of histamine H(1), H(2) and H(3) receptor antagonists on the skeletal system in rats were differential and dependent on estrogen status.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland. Electronic address: jfolwarczna@sum.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Folwarczna
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Janas
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Pytlik
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Śliwiński
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Wiercigroch
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Katowice, Sosnowiec, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Brzęczek
mesh_terms: D000818:Animals; D001621:Betahistine / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects; D005260:Female; D017336:Loratadine / Q000494:pharmacology; D010052:Ovariectomy; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011968:Receptors, Histamine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D011968:Receptors, Histamine; D017336:Loratadine; D011899:Ranitidine; D001621:Betahistine
keywords: Betahistine; Bone mechanical properties; Histamine receptor antagonists; Loratadine; Ranitidine