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

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Abstract

Introduction

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.

Materials and methods

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.

Results

Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18 weeks 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 18 weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice.

Conclusion

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.

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Acknowledgements

This work was supported by CREST-Nanomechanics: Elucidation of macroscale mechanical properties based on understanding nanoscale dynamics for innovative mechanical materials (Grant Number: JPMJCR2194) from the Japan Science and Technology Agency (JST), and a Grant-in-Aid for Scientific Research (JP23H00235) from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Yuki Mihara, Takao Omura, Yu Yamato, Tomohiro Yamada, Ayako Okamoto & Yukihiro Matsuyama

  2. Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1, Yamada-Oka, Suita, Osaka, 565-0871, Japan

    Takuya Ishimoto, Ryosuke Ozasa & Takayoshi Nakano

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  1. Yuki Mihara
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Contributions

YM and TN conceptualized and supervised the study and reviewed and edited the manuscript. RO, TO, YY, TY, and AO collected the data. YM and TI wrote the manuscript. All the authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Yukihiro Matsuyama or Takayoshi Nakano.

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Ethical approval

This study was approved by the Animal Care and Use Committee of Hamamatsu University School of Medicine (approval number: 2019002).

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Mihara, Y., Ishimoto, T., Ozasa, R. et al. Deterioration of apatite orientation in the cholecystokinin B receptor gene (Cckbr)-deficient mouse femurs. J Bone Miner Metab 41, 752–759 (2023). https://doi.org/10.1007/s00774-023-01460-9

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  • DOI: https://doi.org/10.1007/s00774-023-01460-9

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