Deterioration of apatite orientation in the cholecystokinin B receptor gene (Cckbr)-deficient mouse femurs.

Abstract

The discrepancy between bone mineral density (BMD), the gold standard for bone assessment, and bone strength is a constraint in diagnosing bone function and determining treatment strategies for several bone diseases. Gastric hypochlorhydria induced by clinically used proton pump inhibitor (PPI) therapy indicates a discordance between changes in BMD and bone strength. Here, we used Cckbr-deficient mice with gastric hypochlorhydria to examine the effect of gastric hypochlorhydria on bone mass, BMD, and preferential orientation of the apatite crystallites, which is a strong indicator of bone strength. Cckbr-deficient mice were created, and their femurs were analyzed for BMD and preferential orientation of the apatite c-axis along the femoral long axis. Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18weeks of age; however, BMD was comparable to that of wild-type mice. In contrast, apatite orientation in the femur mid-shaft significantly decreased from 9 to 18weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice. Lesions in Cckbr-deficient mice occurred earlier in apatite orientation than in bone mass. Hence, bone apatite orientation may be a promising method for detecting hypochlorhydria-induced osteoporosis caused by PPI treatment and warrants urgent clinical applications.