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Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy

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Abstract

Summary

We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice.

Introduction

Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification.

Methods

Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b−/−) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism.

Results

Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria.

Conclusion

Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.

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Acknowledgments

We thank Dr. rer. medic. Björn Busse and Dr. med. dent. Till Koehne for their contribution to assess mineralization data of gastrectomized patients and controls. This work was supported by grants from the German Research Foundation (AM 103/14-2) and the German Federal Ministry of Education and Research within the framework of the project “Molecular Pathology of Osteoporosis” (BMBF, Osteopath 01EC1006) to MA.

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Authors and Affiliations

  1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestr. 59, 22529, Hamburg, Germany

    M. Krause, J. Keller, F. Barvencik, T. Schinke & M. Amling

  2. Department of Trauma and Reconstructive Surgery, Asklepios Clinic St. Georg, Hamburg, Germany

    M. Krause

  3. Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    B. Beil

  4. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia

    I. van Driel

  5. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    J. Zustin

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  1. M. Krause
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Correspondence to M. Amling.

Additional information

Drs. Krause and Keller contributed equally and therefore share first authorship.

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Supplementary Fig. 1

Coefficients of variation of histomorphometric analysis of undecalcified bone sections of controls and gastrectomized patients (PDF 65 kb)

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Krause, M., Keller, J., Beil, B. et al. Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy. Osteoporos Int 26, 987–995 (2015). https://doi.org/10.1007/s00198-014-2965-1

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