Response of Adult Patients with Osteomalacia to Treatment with Crystalline 1α-Hydroxy Vitamin D3

Abstract

Preparation of synthetic sterols with hydroxyl groups in key positions on the sterol molecule opens the possibility of developing new antirachitic sterols to treat metabolic bone disease in man. One of the first of these that has been pre-prepared in crystalline form is 1α-hydroxy vitamin D₃. We examined its effects in human subjects suffering from osteomalacia. The intravenous administration of 2.5 to 5.0 μg per 24 hours of pure crystalline 1α-hydroxy vitamin D₃ to four human subjects with vitamin-D-deficient osteomalacia induced a rise in serum phosphorus, an inconsistent effect on serum calcium, a decrease in urinary phosphate excretion, a decrease in the fecal excretion of both calcium and phosphorus, and a late rise in urinary hydroxyproline excretion. Phosphate clearance was decreased in all subjects. Bone biopsies were performed before and eight to 10 days after 1α-hydroxy vitamin D₃ therapy. Quantitative histologic analysis showed that active bone resorption and active bone formation both increased, and the percentage of the total osteoid surface bearing a calcification front was also increased. These results indicate that 1α-hydroxy vitamin D₃ is an active antirachitic agent in man. (N Engl J Med 291:866–871, 1974)