Metabolic effects of synthetic calcitriol (Rocaltrol^®) in the treatment of postmenopausal osteoporosis

The long-term safety and efficacy of synthetic 1,25-(OH)₂D₃ (calcitriol; Rocaltrol^®) in the treatment of women with type 1 osteoporosis is being assessed in a randomized trial. Patients were allocated in double-blind fashion to 1,25-(OH)₂D₃ or matching placebo. Initially, the calcium intake was adjusted to 1,000 mg/d. The study protocol called for increasing the dose of 1,25-(OH)₂D₃ until patients developed either hypercalcemia or hypercalciuria. However, in order to maintain a higher dose of calcitriol on a long-term basis, the calcium intake had to be reduced to 600 mg/d in those receiving calcitriol; if that was not successful in eliminating hypercalcemia and hypercalciuria, then the dose of 1,25-(OH)₂D₃ was reduced as necessary. During the hypercalcemic phase, the indices of bone resorption decreased significantly, demonstrating that calcium absorption is solely responsible for hypercalcemia. The maintenance dose was established after 8 to 10 weeks, and the 24-hour urine calcium and creatinine clearance remained constant throughout the remainder of the study period. On a calcium intake of 600 mg/d, the long-term maintenance dose of 1,25-(OH)₂D₃ averaged 0.675 μg/d. Long-term therapy on an average dose of 0.675 μg/d was not associated with nephrotoxicity.