Goodman W G, Ramirez J A, Belin T R, Chon Y, Gales B, Segre G V, Salusky I B
Department of Radiology, UCLA School of Medicine.
Kidney Int. 1994 Oct;46(4):1160-6. doi: 10.1038/ki.1994.380.
Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 microns2/mm2/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis.
间歇性骨化三醇疗法常用于治疗接受定期透析患者的继发性甲状旁腺功能亢进，但关于骨组织对这种治疗方式的组织学反应，现有信息很少。因此，对14例经活检证实为继发性甲状旁腺功能亢进的儿童和青少年，给予间歇性口服或腹腔内注射骨化三醇治疗12个月。在整个研究过程中，每月测量包括血清完整甲状旁腺激素水平在内的矿物质代谢生化指标，并在治疗结束时重复进行骨活检。治疗前，11例患者有纤维性骨炎，3例有轻度继发性甲状旁腺功能亢进病变。14例患者中有12例出现组织学改善，11例中的10例纤维性骨炎消退。在间歇性骨化三醇治疗期间，所有患者的骨形成均减少，从861±380降至150±170μm²/mm²/天，P<0.001。6例患者的骨形成降至正常，但6例患者出现骨无动力性病变，骨形成率低于正常。发生骨无动力性病变的患者血清甲状旁腺激素和碱性磷酸酶水平下降，但在随访评估中，骨形成率正常的患者这些值仍升高。骨无动力性病变患者的骨化三醇平均剂量和每千克体重平均剂量均无差异。因此，在间歇性骨化三醇治疗期间，相当一部分患者会发生骨无动力性肾性骨营养不良。尽管血清甲状旁腺激素和碱性磷酸酶水平下降提示骨无动力性病变的发生，但一些患者尽管血清甲状旁腺激素水平持续升高，骨形成仍减少。对于接受腹膜透析的患者，大剂量给予骨化三醇时，可能会直接抑制继发性甲状旁腺功能亢进患者的成骨细胞活性。
