Therapy for
X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by
hyperparathyroidism. 24,25(
OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(
OH)2 D3 supplementation to standard treatment in patients with XLH to improve
bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(
OH)2 D3 or
dihydrotachysterol plus
phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(
OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of
calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(
OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(
OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum
phosphorus was slightly greater with 24,25(
OH)2 D3. Radiographic features of
rickets improved during 24,25(
OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(
OH)2 D3 is a useful adjunct to standard
therapy in XLH by effecting correction of
hyperparathyroidism and improvement of
rickets and
osteomalacia.