Daily
calcitriol therapy has been reported to improve linear growth in children with renal
bone disease, and
1,25-dihydroxyvitamin D is a key regultor of chondrocyte proliferation and differentiation. Whereas large intermittent doses of
calcitriol can lower serum
parathyroid hormone (PTH) levels and reverse the skeletal changes of
secondary hyperparathyroidism, the impact of intermittent
calcitriol therapy on linear growth in children is not known. Thus, we studied 16 pre-pubertal patients with bone biopsy-proven
secondary hyperparathyroidism who completed a 12-month prospective clinical trial of intermittent
calcitriol therapy. Biochemical results and growth data obtained during intermittent
calcitriol therapy were compared to values determined during the preceding 12 months of daily
calcitriol therapy in each study subject; changes in bone histology were assessed after one year of intermittent
calcitriol therapy. Z-scores for height did not change during 12 months of daily
calcitriol therapy. Although the skeletal lesions of
secondary hyperparathyroidism improved in most patients, Z-scores for height decreased from -1.8 +/- 0.32 to -2.0 +/- 0.33, P < 0.01, during intermittent
calcitriol therapy. The largest reductions were seen in patients who developed adynamic bone lesions after 12 months of treatment. Delta 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 intermittent
calcitriol therapy but not during daily
calcitriol therapy. The data suggest that high dose intermittent
calcitriol therapy adversely affects linear growth, particularly in patients with the adynamic lesion. The higher doses of
calcitriol or the intermittent schedule of
calcitriol administration may directly inhibit chondrocyte activity within growth plate cartilage of children with
end-stage renal disease.