Alterations in osteoclast morphology following osteoprotegerin administration in the magnesium-deficient mouse.
In the present study, we used osteoprotegerin (OPG), which blocks osteoclastogenesis, to correct and thus explain the hypercalcemia that is seen during dietary Mg deficiency in the mouse. Control and Mg-deficient mice received injections for 12 days of either OPG or vehicle only. Serum Ca was similar in Mg-deficient mice treated with OPG and in control mice receiving OPG (9.2 +/- 0.3 mg/dl vs. 9.2 +/- 0.5). Both groups had significantly higher serum Ca than controls or Mg-deficient animals receiving vehicle alone. Surprisingly, Mg-depleted mice that received OPG in doses that inhibit osteoclastic bone resorption remained hypercalcemic. Because mature osteoclasts still present in the marrow might be hyperactive, we examined osteoclast morphology at the light microscopic and ultrastructural level. Light microscopic examination of trabecular bone showed few osteoclasts in OPG-treated mice. Ultrastructural examination revealed that osteoclasts in OPG-treated mice have decreased contact with the endosteal bone surface and absence of a ruffled border. Because the morphology of the existing pool of mature osteoclasts did not enhance resorption, another mechanism, such as increased intestinal absorption of Ca in Mg-deficient mice, likely contributes to the hypercalcemia observed during Mg deficiency.
Department of Orthopaedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA. hgruber@carolinas.org
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D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006934:Hypercalcemia / Q000209:etiology*; D007527:Isoenzymes / Q000032:analysis; D008275:Magnesium Deficiency / Q000150:complications* / Q000473:pathology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D000071681:Tartrate-Resistant Acid Phosphatase
D006023:Glycoproteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium