DEVELOPMENT OF ADYNAMIC BONE IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AFTER INTERMITTENT CALCITRIOL THERAPY

Intermittent calcitriol therapy is commonly used to treat secondary hy perparathyroidism in patients undergoing regular dialysis, but there i s little available information about the histologic response of bone t o this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermit tent oral or intraperitoneal doses of calcitriol for 12 months. Bioche mical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were rep eated at the end of treatment. Before treatment, 11 patients had ostei tis fibrosa and three had mild lesions of secondary hyperparathyroidis m. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all pa tients during intermittent calcitriol therapy, falling from 861 +/- 38 0 to 150 +/- 170 mu m(2)/mm(2)/day, P < 0.001. Bone formation decrease d to normal in six patients, but six patients developed adynamic lesio ns of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone format ion at follow-up evaluation. Neither the mean dose of calcitriol nor t he average dose per kilogram body weight differed in patients with ady namic lesions. Thus, adynamic renal osteodystrophy develops in a subst antial number of patients during intermittent calcitriol therapy. Alth ough declining serum PTH and alkaline phosphatase levels suggest the d evelopment of the adynamic lesion, bone formation decreases in some pa tients despite persistently high serum PTH levels. Calcitriol may dire ctly suppress osteoblastic activity in patients with secondary hyperpa rathyroidism when given in large doses to patients undergoing peritone al dialysis.