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Exercise-induced hypercalcemia and vasopressin-mediated bone resorption

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Abstract

Summary

Our human observational study showed that elevated arginine vasopressin levels by heavy exercise, not catecholamines, were associated with elevated serum tartrate-resistant acid phosphatase 5b (TRACP-5b). The increase in serum calcium was positively associated with percent changes of TRACP-5b, implying the involvement of bone resorption in the pathogenesis of exercise-induced hypercalcemia.

Introduction

It remains unclear whether enhanced bone resorption explains exercise-induced hypercalcemia. An experimental study demonstrated that arginine vasopressin (AVP) stimulated osteoclast activity.

Methods

We conducted a prospective observational study, enrolling 65 trained healthy male officers of the Japan Self-Defense Forces (34 and 31 in waves 1 and 2, respectively). Before and after a 5-h heavy exercise, we collected laboratory data including bone markers, symptoms, and ionized calcium (iCa; wave 2 only). As blood calcium levels change after exercise, we estimated calcium (corrected calcium) levels immediately after the exercise using the correlation between blood calcium and time from the end of exercise in another cohort.

Results

Body weight decreased by 6.9% after the exercise. Corrected post-exercise serum total calcium (tCa) and iCa levels were significantly higher than pre-exercise levels, and 18% of participants showed hypercalcemia defined as corrected tCa >10.4 mg/dL or iCa >1.30 mmol/L. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), plasma three fractions of catecholamines, and AVP elevated significantly (median 14.3 pg/mL), while procollagen type 1 N-terminal propeptide and whole parathyroid hormone showed significant decreases. Corrected tCa increase showed a non-linear positive association with percent changes of TRACP-5b (%ΔTRACP-5b) even after adjustment for confounders. In addition, %ΔTRACP-5b was not associated with catecholamines, but with post-exercise AVP levels after adjustment for pre-exercise TRACP-5b. Symptoms of nausea or vomiting (observed in 20%) were positively associated with corrected post-exercise iCa after adjustment for post-exercise blood pH.

Conclusion

AVP elevation may explain bone resorption and the following hypercalcemia in the setting of heavy exercise.

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Data availability

The datasets of this study are not publicly available due to data protection by Self-Defense Forces Central Hospital. However, these are available from the corresponding author on reasonable request.

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Acknowledgements

We are deeply grateful to members of the Japan Self Defense Forces Central Hospital: Research Department (especially Mrs. Seiji Fujimura, Michio Nakai, Shigeru Kashiwabara, Masao Chiba, Takashi Suzuki, Drs. Hiroki Omura, Yasunori Mizuguchi, and Shigeto Takeshima) for planning and collecting samples, Clinical Laboratory (especially Mrs. Makoto Nemoto, Tadakazu Osaka, Nobuyoshi Kaito, Daisuke Izumiyama, Akio Nagashima, Ms. Tomomi Hori, Tomoko Takahashi, and Dr. Takao Kubota) for laboratory measurement, Health Care Center (especially Mr. Masahiro Kato, Ms. Akemi Yagi, and Dr. Susumu Matsukuma) for paper work, and Department of Gastroenterological Medicine (especially Dr. Shigeaki Aono) for collaboration. We would like to thank members of the Education Department of Japan Ground Self Defense Forces Medical Serves School (especially Drs. Satoshi Mimura, Mikio Takeshima, and Yoshitaro Matsushita) for the advice. Finally, we would like to express our deepest gratitude and respect to the participants in this study.

Code availability

The statistical analyses were performed using Stata/SE 13.0 software (Stata Corp).

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Authors and Affiliations

  1. Health Care Division, Health and Counseling Center, Osaka University, Osaka, Japan

    M. Senda & T. Moriyama

  2. Department of Internal Medicine, Self-Defense Forces Central Hospital, Tokyo, Japan

    M. Senda & T. Ito

  3. Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan

    T. Hamano

  4. Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan

    T. Hamano, I. Matsui & Y. Isaka

  5. Department of Nephrology, Hyogo Prefectural Nishinomiya Hospital, Hyogo,, Japan

    N. Fujii

  6. Department of Inter-Organ Communication Research in Kidney Disease, Osaka University Graduate School of Medicine, Osaka, Japan

    Y. Sakaguchi

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  1. M. Senda
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Corresponding author

Correspondence to T. Hamano.

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Ethics approval

Our study was carried out in accordance with the Declaration of Helsinki and received ethical approval by the ethics committee of the Japan Self-Defense Forces Central Hospital (approval number: 29-023).

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Written informed consent was obtained from all participants before the enrollment.

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Senda, M., Hamano, T., Fujii, N. et al. Exercise-induced hypercalcemia and vasopressin-mediated bone resorption. Osteoporos Int 32, 2533–2541 (2021). https://doi.org/10.1007/s00198-021-06030-1

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