Decreased bone mineral density and reduced bone quality in H+/K+ ATPase beta-subunit deficient mice

作者：Fossmark Reidar^*; Stunes Astrid K; Petzold Christiane; Waldum Helge L; Rubert Marina; Lian Aina Mari; Reseland Janne E; Syversen Unni

来源：Journal of Cellular Biochemistry, 2012, 113(1): 141-147.

DOI：10.1002/jcb.23337

• Proton pump inhibitors
• Osteoporosis
• Parathyroid hormone

Proton pump inhibitors (PPIs) are widely used against gastroesophageal reflux disease. Recent epidemiological studies suggest that PPI users have an increased risk of fractures, but a causal relationship has been questioned. We have therefore investigated the skeletal phenotype in H+/K+ATPase beta-subunit knockout (KO) female mice. Skeletal parameters were determined in 6- and 20-month-old KO mice and in wild-type controls (WT). Whole body bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry (DXA). Femurs were examined with mu CT analyses and break force were examined by a three-point bending test. Plasma levels of gastrin, RANKL, OPG, osteocalcin, leptin, and PTH were analyzed. KO mice had lower whole body BMC at 6 months (0.53 vs. 0.59g, P=0.035) and at 20 months (0.49 vs. 0.74g, P%26lt;0.01) compared to WT as well as lower BMD at 6 months (0.068 vs. 0.072g/cm2, P=0.026) and 20 months (0.067 vs. 0.077 g/cm2, P%26lt;0.01). Mechanical strength was lower in KO mice at the age of 20 months (6.7 vs. 17.9 N, P%26lt;0.01). Cortical thickness at 20 months and trabecular bone volume% at 6 months were significantly reduced in KO mice. Plasma OPG/RANKL ratio and PTH was increased in KO mice compared to controls. H+/K+ATPase beta subunit KO mice had decreased BMC and BMD, reduced cortical thickness and inferior mechanical bone strength. Whereas the mechanism is uncertain, these findings suggest a causal relationship between long-term PPI use and an increased risk of fractures. J. Cell. Biochem. 113: 141147, 2012.

• 出版日期2012-1