22-Oxacalcitriol suppresses secondary hyperparathyroidism without inducinglow bone turnover in dogs with renal failure

Background. Calcitriol therapy suppresses serum levels of parathyroid hormo ne (PTH) in patients with renal failure but has several drawbacks, includin g hypercalcemia and/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertake n to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. Methods. Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operate d (Sham, N = 22). The animals received supplemental phosphate to enhance PT H secretion. Fourteen weeks after the start of phosphate supplementation, h alf of the Nx and Sham dogs received doses of OCT (three times per week); t he other half were given vehicle for 60 weeks. Thereafter, the treatment mo dalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism wer e measured throughout the study, and bone biopsies were done at baseline, 6 0 weeks after OCT or vehicle treatment, and at the end of the crossover per iod. Results. In Nx dogs, OCT significantly decreased serum PTH levels soon afte r the induction of renal insufficiency. In longstanding secondary hyperpara thyroidism, OCT (0.03 mu g/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects wer e accompanied by episodes of hypercalcemia and hyperphosphatemia, In animal s with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 mu g/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly mineralization lag time, (t hat is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. Conclusions. These results indicate that even though OCT does not completel y prevent the occurrence of hypercalcemia in experimental dogs with renal i nsufficiency, it may be of use in the management of secondary hyperparathyr oidism because it does not induce low bone turnover and, therefore, does no t increase the risk of adynamic bone disease.