Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD

Abstract

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.

Sevelamer Controls Parathyroid Hormone–Induced Bone Disease as Efficiently as Calcium Carbonate without Increasing Serum Calcium Levels during Therapy with Active Vitamin D Sterols

“…Overall, the magnitude of reduction in bone formation did not differ between groups, but the decline in bone resorption was greater in the calcium-treated group, which could be consistent with a PTH-independent role of calcium in the regulation of osteoclastic activity (29). The prevention of adynamic bone has important clinical implications, because a substantial proportion of pediatric patients who were treated with calcitriol and calciumbased binders developed this lesion associated with more frequently elevated serum calcium levels and growth retardation (3,26,30). Furthermore, adynamic osteodystrophy was reported to be associated with greater degree of arterial calcifications (5).…”

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

“…All of the subjects were part of various clinical investigations to characterize the spectrum of renal osteodys-trophy in pediatric dialysis patients (3,(7)(8)(9)(10)(11); only baseline biopsies were used for the current analysis. All patients received calcium-based phosphate binders at the time of the bone biopsy, and in those treated with daily oral calcitriol, such therapy was held for 4 weeks before bone biopsy.…”

A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

“…It has been suggested that intermittent calcitriol therapy combined with calcium-containing phosphate binders may adversely affect chondrocyte activity in the epiphyseal growth plate, with a consequent reduction in linear growth. Studies on the relations between adynamic bone, suppression of PTH with vitamin D therapies, and growth in children have yielded conflicting results [15][16][17].…”