Sanchez C P, He Y Z
Department of Pediatrics, University of Wisconsin, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
Kidney Int. 2007 Sep;72(5):582-91. doi: 10.1038/sj.ki.5002375. Epub 2007 Jun 6.
Calcitriol is a standard therapy for secondary hyperparathyroidism in chronic renal failure. We evaluated whether the effect of daily or intermittent calcitriol administration is more efficient in enhancing bone growth in renal failure with advanced secondary hyperparathyroidism in weanling 5/6 nephrectomized rats loaded with phosphorus to induce severe secondary hyperparathyroidism. The animals were treated daily or three times weekly with calcitriol for 4 weeks but the total weekly dose of calcitriol was the same. Although calcitriol increased the serum calcium, it did not lower parathyroid hormone (PTH) or improve tibia and body length. Animals with renal failure and advanced secondary hyperparathyroidism had decreased PTH/PTHrP, which was accompanied by an increase in the cyclin kinase inhibitor p57(Kip2). Calcitriol treatment upregulated the PTH/PTHrP receptor but also increased inhibitors of cell proliferation such as p21(Waf1/Cip1), IGFBP3, and FGFR3. Calcitriol also enhanced markers of chondrocyte differentiation, such as IGF1, Vitamin D receptor, FGF23, and bone morphogenetic protein-7. Receptor activator of nuclear factor-kappabeta ligand levels improved with calcitriol treatment but without changes in osteoprotegerin suggesting an enhancement of osteo/chondroclastogenesis and mineralization. Overall, both daily and intermittent calcitriol had similar effects on endochondral bone growth in phosphorus-loaded rats with renal failure.
骨化三醇是慢性肾衰竭继发性甲状旁腺功能亢进的标准治疗药物。我们评估了在诱导严重继发性甲状旁腺功能亢进的磷负荷断奶5/6肾切除大鼠中，每日或间歇性给予骨化三醇在促进肾衰竭伴晚期继发性甲状旁腺功能亢进的骨生长方面是否更有效。动物每天或每周三次接受骨化三醇治疗，持续4周，但骨化三醇的每周总剂量相同。尽管骨化三醇增加了血清钙，但它并没有降低甲状旁腺激素（PTH）或改善胫骨和体长。患有肾衰竭和晚期继发性甲状旁腺功能亢进的动物PTH/PTHrP降低，同时细胞周期蛋白激酶抑制剂p57(Kip2)增加。骨化三醇治疗上调了PTH/PTHrP受体，但也增加了细胞增殖抑制剂，如p21(Waf1/Cip1)、IGFBP3和FGFR3。骨化三醇还增强了软骨细胞分化标志物，如IGF1、维生素D受体、FGF23和骨形态发生蛋白-7。骨化三醇治疗后核因子-κB受体激活剂配体水平有所改善，但骨保护素没有变化，提示骨/软骨破骨细胞生成和矿化增强。总体而言，每日和间歇性给予骨化三醇对磷负荷肾衰竭大鼠的软骨内骨生长具有相似的作用。
