Bone Response to Phosphate Salts, Ergocalciferol, and Calcitriol in Hypophosphatemic Vitamin D-Resistant Rickets

We treated 11 children with vitamin D–resistant rickets with a phosphate mixture either alone (1.2 to 3.6 g per day) or combined with ergocalciferol (vitamin D2, 25 to 50×103 IU per day) or with calcitriol (1,25-dihydroxyvitamin D3, 0.25 to 1 μg per day). Serum calcitriol concentrations were normal in all patients. Calcitriol therapy raised circulating levels of the hormone to values above normal and increased intestinal phosphate absorption. In some patients this regimen decreased the need for phosphate supplements. None of the treatment regimens corrected the renal phosphate leak. Radiologic studies and bone histomorphometric analyses showed that phosphate (alone or with ergocalciferol) induced the mineralization of the growth plate but not of the endosteal bone surface. Combined calcitriol and phosphate therapy for a total of 2850 patient-days greatly improved the mineralization of trabecular bone. Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage. The data indicate that the combined calcitriol and phosphate regimen is useful in the treatment of vitamin D–resistant rickets. (N Engl J Med. 1980; 303: 1023–31.) ALTHOUGH the exact nature of the basic defect underlying the classic form of vitamin D–resistant rickets (VDRR)1 is a matter of continuing debate, it is accepted that its hallmark, hypophosphatemia, is caused by a primary defect in renal transport of phosphate.2 Accordingly, therapeutic attempts have stressed the importance of phosphate-rich regimens as an adjunct to large daily doses of vitamin D.3,4 The observed effect of these treatments on bone has been limited in most cases to radiologic changes in the metaphyseal areas of the long bones. Although there have been reports that abnormal trabecular and periosteocytic mineralization was not affected. © 1980, Massachusetts Medical Society. All rights reserved.