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


BACKGROUND
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.


CONCLUSIONS
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.
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestr. 59, 22529, Hamburg, Germany.
M
M
Krause
J
J
Keller
B
B
Beil
I
I
van Driel
J
J
Zustin
F
F
Barvencik
T
T
Schinke
M
M
Amling
D000126:Achlorhydria / Q000188:drug therapy; D000368:Aged; D000818:Animals; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002125:Calcium Gluconate / Q000494:pharmacology / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007085:Ilium / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies
D002219:Carbamates; C070766:carbamic acid; D002125:Calcium Gluconate; D002118:Calcium