Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H super(+)/K super(+)ATPase Beta Subunit KO Mice
Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H super(+)/K super(+)ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compar...
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| Published in: | Journal of cellular biochemistry Vol. 117; no. 9; pp. 2089 - 2096 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
01-09-2016
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| Online Access: | Get full text |
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| Summary: | Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H super(+)/K super(+)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 mu CT. 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 3mg/kg did not rescue the osteoporotic phenotype in H super(+)/K super(+)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. Epidemiological studies have shown increased fracture risk in individuals with gastric anacidity. Low gastric acid levels result in elevated gastrin and subsequent stimulation of gastric histamine release. In a mouse model of gastric anacidity, we find no improvement of bone quality after histamine 1 receptor administration. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
| ISSN: | 0730-2312 1097-4644 |
| DOI: | 10.1002/jcb.25514 |