title: Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H(+) /K(+) ATPase Beta Subunit KO Mice.
abstract: Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by μCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. © 2016 Wiley Periodicals, Inc.
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.
authors: Kristin M
authors: KM
authors: Aasarød
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.
authors: Astrid K
authors: AK
authors: Stunes
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.
authors: Mats P
authors: MP
authors: Mosti
authors: Department of Structural Engineering, NTNU, Trondheim, Norway.
authors: Masoud
authors: M
authors: Ramezanzadehkoldeh
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.
authors: Bjørn I
authors: BI
authors: Viggaklev
authors: Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway.
authors: Janne E
authors: JE
authors: Reseland
authors: Department of Structural Engineering, NTNU, Trondheim, Norway.
authors: Bjørn H
authors: BH
authors: Skallerud
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.|Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim, Norway.
authors: Reidar
authors: R
authors: Fossmark
authors: Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway.|Department of Endocrinology, St. Olav's Hospital, Trondheim, Norway.
authors: Unni
authors: U
authors: Syversen
mesh_terms: D000818:Animals; D017332:Cetirizine / Q000494:pharmacology*; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000172:deficiency*; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine; D017506:H(+)-K(+)-Exchanging ATPase; D017332:Cetirizine
keywords: ANACIDITY; ANTIHISTAMINE; BONE; GASTRIN; HISTAMINE; HISTAMINE 1 RECEPTOR