A role for the intestine in the bone disease of juvenile X-linked hypophosphatemic mice: malabsorption of calcium and reduced skeletal mineralization.
Low duodenal vitamin D-dependent calcium-binding protein has been reported in juvenile Hyp mice. Levels of this protein improved in adult Hyp mice. This led to the search for possible abnormal intestinal calcium absorption in juvenile Hyp mice and for evidence that calcium malabsorption, if present, would exacerbate the bone disease. A balance study was performed in 10 sets of normal and Hyp male mice at 5 and 12 weeks of age. Twelve-week-old Hyp mice had balances (24-h intake minus excretion) of Ca, P, Mg, Na, and K that were not significantly different from those of 12-week-old normal mice. However, 5-week-old Hyp mice had a significantly lower balance of Ca with higher fecal Ca and lower urinary Ca. No balance was also lower due to higher fecal Na. The balances of P, Mg, and K were not significantly affected in young Hyp mice. Growth and mineralization of the femur were compared in normal and heterozygous female Hyp mice from 3.5-46 weeks of age. The femora of Hyp mice gained ash weight at a rate comparable to that for normal mice, except for a lag between 3.5 and 7 weeks. There was life-long hypophosphatemia and elevated plasma alkaline phosphatase. It was concluded that the period of low levels of duodenal vitamin D-dependent calcium-binding protein was associated with low intestinal absorption and low skeletal mineralization. This dysfunction of the intestine in juvenile, rapidly growing Hyp mice may exacerbate the bone disease.
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D007015:Hypophosphatemia, Familial / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D007408:Intestinal Absorption; D008274:Magnesium / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008903:Minerals / Q000378:metabolism*; D010710:Phosphates / Q000097:blood; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D008903:Minerals; D010710:Phosphates; D012964:Sodium; D000469:Alkaline Phosphatase; D008274:Magnesium; D011188:Potassium; D002118:Calcium