Supranormal 25-hydroxyvitamin D and subnormal 1,25-dihydroxyvitamin D: their role in X-linked hypophosphatemic rickets.

Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) and bone mineral content by the photon-absorption technique were determined in eight patients with X-linked hypophosphatemic rickets treated for at least 24 months with oral sodium phosphate and high-dosage ergocalciferol (vitamin D2). Mean 25-OH-D2 level was 129.5 +/- 67.5 ng/mL (mean +/- SD); the level of 25-OH-D3 was 10.5 +/- 5.8 ng/mL. These values were significantly higher than in normal subjects (total 25-OH-D mean of 27 +/- 10 ng/mL). Serum 1,25-(OH)2D was 16.9 +/- 8.5 pg/mL (mean +/- SD) in the eight patients, significantly lower than 47 +/- 16 pg/mL in 27 age-matched controls. Values indicative of significant demineralization were found in seven of the eight phsophate-treated patients, who had no radiologic evidence of rickets. These results suggest that any theory of the pathogenesis of this disorder must account for inappropriate renal vitamin D metabolism and for renal hyperphosphaturia. The failure of high-dosage oral phosphate and ergocalciferol to fully correct demineralization may suggest a role for calcitriol (1,25-(OH)2D3) as a therapeutic agent.