Long-Term Influence of Calcitriol (1,25-Dihydroxyvitamin D) and Supplemental Phosphate in X-Linked Hypophosphatemic Rickets

Abstract

Ten patients with hypophospathemic rickets (8 with X-linked familial form) were treated with vitamin D2 (10,000-75,000 units/day) and oral phosphate (1.5-3.6 gm) for a total of 438 treatment mo. Therapy was then changed to calcitriol (17-34 ng/kg per day) and the same phosphate dose. Patients served as their own controls, and significant biochemical changes noted were an increase in immunoreactive parathyroid hormone from 29 .+-. 9 (SD) .mu.IEq/ml (pre-phosphate) to 62 .+-. 34 on vitamin D2 plus PO4, then decreasing to 40 .+-. 20 on a regimen of 1,25-dihydroxyvitamin D (1,25(OH)2D) plus PO4; serum PO4 rose from 2.44 .+-. 0.45 (SD) mg/100 ml to 3.06 .+-. 0.79 and then to 3.43 .+-. 0.76; alkaline phosphatase activity decreased from 677 .+-. 298 (SD) IU/liter to 457 .+-. 183 to 290 .+-. 176. Serum Ca and creatinine levels were unchanged. Both urinary Ca excretion and Ca creatinine ratio decreased after therapy with 1,25(OH)2D. Urinary phosphate excretion was higher after calcitriol administration. Serum 1,25(OH)2D levels were low in these vitamin D2-treated patients, and an inverse relationship between serum 25(OH)2D and 1,25(OH)2D was found. Improved bone mineralization was evident from serial assessment by photon absorptiometry, and radial bone mineral content rose from 75.3% .+-. 2.2% of expected to 82.2% .+-. 1.4% (P L 0.005). Stature was improved when assessed by standard deviation for chronologic age but did not reach statistical significance. Long-term 1,25(OH)2D plus phosphate therapy appears to be more efficacious than vitamin D2 in this form of rickets, particular in improving phosphate homeostasis.