Hypophosphatemia and the development of rickets in osteopetrotic (op/op) mice.
Our previous work has shown that op/op mice hyperabsorb dietary calcium in the vitamin D-deficient state and shunt that calcium into bone. Under these conditions, the op/op mice are hypocalcemic. The purpose of this study was to examine calcium metabolism and bone mineralization in vitamin D-deficient op/op mice. First, the op/op mice and their normal littermates were placed on a vitamin D-deficient, low phosphorus diet to limit bone mineralization. Under these circumstances, op/op mice survived, even when calcium was also removed from the diet. If the diet contained phosphate, op/op mice died from hypocalcemic tetany when calcium was also removed from the diet. Furthermore, serum calcium levels became similar to wild type in the op/op mice administered the vitamin D-deficient, low phosphorus diet, and op/op mice were able to increase serum calcium in response to 1,25-dihydroxyvitamin D3. The op/op mice developed rickets when their serum phosphorus level was too low to support bone mineralization. The op/op mice became hypophosphatemic on regimens in which normal mice were able to maintain normal serum phosphorus levels. It appears that the op/op mouse simply requires a higher dietary calcium and phosphorus level to prevent rickets and hypocalcemic tetany since the bone is not available as a source of these minerals. However, the ability of the op/op mouse to mineralize bone at low serum calcium and phosphorus levels remains unexplained.
McCary
L C
LC
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, USA.
Smith
C M
CM
DeLuca
H F
HF
D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology; D002118:Calcium / Q000008:administration & dosage / Q000097:blood; D005260:Female; D008297:Male; D051379:Mice; D010022:Osteopetrosis / Q000097:blood / Q000150:complications* / Q000378:metabolism; D010758:Phosphorus / Q000097:blood / Q000172:deficiency*; D012279:Rickets / Q000209:etiology*; D014808:Vitamin D Deficiency / Q000150:complications
D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium