DIMINISHED LINEAR GROWTH DURING INTERMITTENT CALCITRIOL THERAPY IN CHILDREN UNDERGOING CCPD

Daily calcitriol therapy has been reported to improve linear growth in children with renal bone disease, and 1,25-dihydroxyvitamin D is a ke y regulator of chondrocyte proliferation and differentiation. Whereas large intermittent doses of calcitriol can lower serum parathyroid hor mone (PTH) levels and reverse the skeletal changes of secondary hyperp arathyroidism, the impact of intermittent calcitriol therapy on linear growth in children is not known. Thus, we studied 16 pre-pubertal pat ients with bone biopsy-proven secondary hyperparathyroidism who comple ted a 12-month prospective clinical trial of intermittent calcitriol t herapy. Biochemical results and growth data obtained during intermitte nt calcitriol therapy were compared to values determined during the pr eceding 12 months of daily calcitriol therapy in each study subject; c hanges in bone histology were assessed after one year of intermittent calcitriol therapy. Z-scores for height did not change during 12 month s of daily calcitriol therapy. Although the skeletal lesions of second ary hyperparathyroidism improved in most patients, Z-scores for height decreased from -1.8 +/- 0.32 to -2.0 +/- 0.33, P < 0.01, during inter mittent calcitriol therapy. The largest reductions were seen in patien ts who developed adynamic bone lesions after 12 months of treatment. D elta Z-scores for height correlated with serum PTH, r = 0.71, P < 0.01 , and alkaline phosphatase levels, r = 0.67, P < 0.01, during intermit tent calcitriol therapy but not during daily calcitriol therapy. The d ata suggest that high dose intermittent calcitriol therapy adversely a ffects linear growth, particularly in patients with the adynamic lesio n. The higher doses of calcitriol or the intermittent schedule of calc itriol administration may directly inhibit chondrocyte activity within growth plate cartilage of children with end-stage renal disease.