Kuizon B D, Goodman W G, Jüppner H, Boechat I, Nelson P, Gales B, Salusky I B
Department of Pediatrics, UCLA School of Medicine, USA.
Kidney Int. 1998 Jan;53(1):205-11. doi: 10.1046/j.1523-1755.1998.00724.x.
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.
据报道，每日服用骨化三醇疗法可改善患有肾性骨病儿童的线性生长，且1,25 - 二羟基维生素D是软骨细胞增殖和分化的关键调节因子。虽然大剂量间歇性服用骨化三醇可降低血清甲状旁腺激素（PTH）水平并逆转继发性甲状旁腺功能亢进的骨骼变化，但间歇性骨化三醇疗法对儿童线性生长的影响尚不清楚。因此，我们研究了16例经骨活检证实为继发性甲状旁腺功能亢进的青春期前患者，他们完成了一项为期12个月的间歇性骨化三醇疗法的前瞻性临床试验。将间歇性骨化三醇治疗期间获得的生化结果和生长数据与每个研究对象在前12个月每日服用骨化三醇治疗期间测定的值进行比较；在间歇性骨化三醇治疗一年后评估骨组织学变化。在每日服用骨化三醇治疗的12个月期间，身高Z值没有变化。虽然大多数患者继发性甲状旁腺功能亢进的骨骼病变有所改善，但在间歇性骨化三醇治疗期间，身高Z值从 - 1.8±0.32降至 - 2.0±0.33，P < 0.01。在治疗12个月后出现骨动力不足性病变的患者中，身高下降最为明显。在间歇性骨化三醇治疗期间，身高的ΔZ值与血清PTH相关，r = 0.71，P < 0.01，与碱性磷酸酶水平相关，r = 0.67，P < 0.01，但在每日服用骨化三醇治疗期间无相关性。数据表明，高剂量间歇性骨化三醇疗法对线性生长有不利影响，尤其是对患有骨动力不足性病变的患者。更高剂量的骨化三醇或间歇性骨化三醇给药方案可能直接抑制终末期肾病儿童生长板软骨内的软骨细胞活性。
