Short-term effects of vitamin D3 and 1,25-dihydroxyvitamin D3 on osteomalacia in uremic rats fed a low calcium-low-phosphorus diet.
The objectives of this study were to evaluate the effects of vitamin D(3) (D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on uremic bone disease independent of their action on the intestine. The histomorphology of tibial metaphyses in uremic (5/6 nephrectomized [5/6 Nx]) rats fed a low-calcium-low-phosphorus (LCLP) diet was compared with sham-operated (SO) rats fed an LCLP diet and 5/6 Nx rats fed an LCLP diet and given 15,000 IU D(3) or 5 units (135 ng) 1,25-(OH)(2)D(3) daily for 7 days. A marked osteomalacia characterized by an increased percentage of active and inactive trabecular osteoid surface and thickened growth plates developed in proximal tibial metaphyses in 5/6 Nx rats given the placebo, compared with SO rats. These bone changes were associated with relative hypophosphatemia, hypophosphaturia, and hypercalciuria in 5/6 Nx rats. In 5/6 Nx rats treated with D(3) or 1,25-(OH)(2)D(3) the growth plates had undergone mineralization and vascular invasion and were markedly reduced in thickness. Other parameters of osteomalacia in trabecular bone were not different from 5/6 Nx rats given the placebo. There was a significant decrease in osteoclasts per millimeter of trabecular surface perimeter in D(3)- and 1,25-(OH)(2)D(3)-treated rats. These bone changes were associated with hypercalcemia, hyperphosphatemia, and hyperphosphaturia, compared with 5/6 Nx rats given the placebo. It was concluded that in uremic rats fed the LCLP diet, shortterm treatment with either pharmacologic levels of D(3) or 1,25-(OH)(2)D(3) corrected only lesions in the growth plate. Osteoid seams were not reduced in treated rats, although the serum calcium-phosphorus product was elevated. The 5/6 Nx rat fed the LCLP diet appears to be a useful model for the rapid induction of uremic osteomalacia in adult animals.
D000818:Animals; D001806:Blood Urea Nitrogen; D002117:Calcitriol; D002118:Calcium / Q000097:blood / Q000172:deficiency / Q000652:urine; D002762:Cholecalciferol / Q000627:therapeutic use*; D004100:Dihydroxycholecalciferols / Q000627:therapeutic use*; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008297:Male; D010018:Osteomalacia / Q000150:complications / Q000188:drug therapy*; D010758:Phosphorus / Q000172:deficiency; D051381:Rats; D013977:Tibia / Q000473:pathology; D013997:Time Factors; D014511:Uremia / Q000150:complications*
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium