Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model
Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model
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DOI：
10.1097/01.asn.0000109671.99498.08
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发表时间：
2004-02-01
影响因子：
13.6
通讯作者：
Hruska, KA
中科院分区：
文献类型：
--
作者：
Lund, RJ;Davies, MR;Hruska, KA
粘连性骨病（ABD）是慢性肾脏病（CKD）的一种重要并发症，病因不明，目前尚无适当的治疗方法。报告了一种伴有ABD的烧蚀性CKD动物模型，其特征在于不存在继发性甲状旁腺功能亢进，并且用骨骼合成代谢因子骨形态发生蛋白-7（BMP-7）成功治疗。对成年小鼠进行右肾电烙术，然后进行左肾切除术。将动物随机分组，喂食正常食物或喂食补充骨化三醇的低磷酸盐食物，以维持CKD中的正常磷酸盐血症。所有组均维持12 wk。如预期，CKD/喂食食物组出现高磷酸盐血症、继发性甲状旁腺功能亢进和轻度骨营养不良。当饮食中的磷被限制，并给予骨化三醇在CKD低磷酸盐/骨化三醇组（ABD），钙，PO 4，和甲状旁腺激素水平保持正常。与假手术组相比，ABD组出现了显著的ABD，其特征在于成骨细胞数量、周长、骨形成率和矿物质沉积率显著降低。BMP-7治疗后骨组织形态计量学异常恢复正常，与ABD组相比有显著性改善（P < 0.05）。假手术低磷/骨化三醇喂养对照组和CKD低磷/骨化三醇/BMP-7组与其他组相比，磷酸盐水平降低（P < 0.05）。在无甲状旁腺功能亢进的CKD小鼠中产生的ABD被骨合成代谢物BMP-7成功逆转，并伴有血浆磷的减少。
An adynamic bone disorder (ABD) is an important complication of chronic kidney disease (CKD) of unknown etiology for which there is no adequate treatment. Reported is an animal model of ablative CKD complicated by an ABD characterized by the absence of secondary hyperparathyroidism and its successful treatment with a skeletal anabolic factor, bone morphogenetic protein-7 (BMP-7). Adult mice were subjected to electrocautery of the right kidney followed by left nephrectomy. Animals were randomized into groups fed normal chow or fed low-phosphate chow supplemented with calcitriol to maintain normophosphatemia in CKD. All groups were maintained on the regimens for 12 wk. Hyperphosphatemia, secondary hyperparathyroidism, and a mild osteodystrophy developed in the CKD/chow-fed group, as expected. When dietary phosphorus was restricted and calcitriol was administered in the CKD low-phosphate/calcitriol group (ABD), Ca, PO4, and parathyroid hormone levels were maintained normal. A significant ABD developed in the ABD group characterized by significant depressions in osteoblast number, perimeters, bone formation rates, and mineral apposition rates when compared with the sham-operated, chow-fed group. The abnormal skeletal histomorphometry was reversed by BMP-7 therapy to normal values and significantly improved from the ABD group (P < 0.05). The sham-operated low-phosphate/calcitriol-fed control group and the CKD low-phosphate/calcitriol/BMP-7 groups had reduced phosphate levels compared with the other groups (P < 0.05). ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphor-us.