The effects of the major vitamin D metabolites upon the resolution of osteomalacia in uremic adult rats

We have previously shown that an osteomalacia dependent upon both a low phosphorus diet and uremia (five-sixth nephrectomy) can be produced rapidly in rats. This is associated with hypophosphatemia and elevated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In order to investigate the role of exogenously administered vitamin D metabolites upon the resolution of this osteomalacia, 72 male Sprague Dawley rats weighting 320 +/- 20 g were subjected to a two-step, subtotal nephrectomy and subsequently fed a diet with low (0.03%) phosphorus (LP) for seven days. Groups of six rats each were then either continued on the LP diet, or switched to a nutrient-matched diet with normal (0.3%) phosphorus (NP) for an additional 10 days. During this time, the rats were infused daily with either: 27 ng 1,25(OH)2D3; 81 ng 24,25 dihydroxyvitamin D3 (24,25(OH)2D3); 135 ng 25 hydroxyvitamin D3 (25(OH)D3); both 27 ng 1,25(OH)2D3 and 81 ng 24,25(OH)2D3; or placebo. Dietary phosphorus repletion was found to reverse the osteomalacia by decreasing the growth plate thickness, the osteoid surface and volume, the osteoid maturation time, serum calcium, and plasma 1,25(OH)2D3, and by increasing the mineralizing surface, bone formation rate, and serum phosphorus. The osteomalacia was also reversed in phosphorus-repleted rats treated with 24,25(OH)2D3, with no additional effects attributable to the 24,25(OH)2D3 itself. Osteomalacia in phosphorus-repleted rats treated with 25(OH)D3 or 1,25(OH)2D3 was only partially reversed; healing was interpreted to be impaired by the elevated plasma 1,25(OH)2D3 levels present in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)