甲状旁腺抑制治疗可使慢性肾脏病引起的皮质骨血管灌注升高恢复正常：一项初步研究。
Parathyroid suppression therapy normalizes chronic kidney disease-induced elevations in cortical bone vascular perfusion: a pilot study.
机构信息
Department of Anatomy and Cell Biology, MS 5035, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN, 46202, USA.
Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA.
出版信息
Osteoporos Int. 2019 Aug;30(8):1693-1698. doi: 10.1007/s00198-019-04974-z. Epub 2019 May 8.
UNLABELLED
Interventions that alter PTH levels in an animal model of chronic kidney disease have effects on the perfusion of bone and bone marrow.
INTRODUCTION
Patients with chronic kidney disease (CKD) have accelerated bone loss, vascular calcification, and abnormal biochemistries, together contributing to an increased risk of cardiovascular disease and fracture-associated mortality. Despite evidence of vascular pathologies and dysfunction in CKD, our group has shown that cortical bone tissue perfusion is higher in a rat model of high-turnover CKD. The goal of the present study was to test the hypothesis that parathyroid hormone (PTH) suppressive interventions would normalize cortical bone vascular perfusion in the setting of CKD.
METHODS
In two separate experiments, 35-week-old CKD animals and their normal littermates underwent intra-cardiac fluorescent microsphere injection to assess the effect of 10 weeks of PTH suppression (Experiment 1: calcium supplementation, Experiment 2: calcimimetic treatment) on alterations in bone tissue perfusion.
RESULTS
In Experiment 1, CKD animals had serum blood urea nitrogen (BUN) and PTH levels significantly higher than NL (+ 182% and + 958%; p < 0.05). CKD+Ca animals had BUN levels that were similar to CKD, while PTH levels were significantly lower and comparable to NL. Both femoral cortex (+ 220%, p = 0.003) and tibial cortex (+ 336, p = 0.005) tissue perfusion were significantly higher in CKD animals when compared to NL; perfusion was normalized to those of NL in CKD+Ca animals. MicroCT analysis of the proximal tibia cortical porosity showed a trend toward higher values in CKD (+ 401%; p = 0.017) but not CKD+Ca (+ 111%; p = 0.38) compared to NL. Experiment 2, using an alternative method of PTH suppression, showed similar results as those of Experiment 1.
CONCLUSIONS
These data demonstrate that PTH suppression-based interventions normalize cortical bone perfusion in the setting of CKD.
目的
改变慢性肾脏病动物模型中甲状旁腺激素（PTH）水平的干预措施对骨骼和骨髓的灌注有影响。
背景
慢性肾脏病（CKD）患者的骨丢失加速、血管钙化和生化异常，共同导致心血管疾病和与骨折相关的死亡率增加。尽管有 CKD 血管病理学和功能障碍的证据，但我们的研究小组已经表明，高转换 CKD 大鼠模型中的皮质骨组织灌注更高。本研究的目的是检验假设，即甲状旁腺激素（PTH）抑制干预措施将使 CKD 中的皮质骨血管灌注正常化。
方法
在两个独立的实验中，35 周龄的 CKD 动物及其正常同窝仔鼠接受心内荧光微球注射，以评估 10 周 PTH 抑制（实验 1：钙补充，实验 2：钙敏感受体激动剂治疗）对骨组织灌注改变的影响。
结果
在实验 1 中，CKD 动物的血清血尿素氮（BUN）和 PTH 水平显著高于 NL（分别升高 182%和 958%；p<0.05）。CKD+Ca 动物的 BUN 水平与 CKD 相似，而 PTH 水平显著降低，与 NL 相当。与 NL 相比，CKD 动物的股骨皮质（增加 220%，p=0.003）和胫骨皮质（增加 336%，p=0.005）组织灌注均显著升高；在 CKD+Ca 动物中，灌注恢复至 NL 水平。对胫骨近端皮质骨孔隙率的 microCT 分析显示，CKD 组（增加 401%；p=0.017）而非 CKD+Ca 组（增加 111%；p=0.38）的骨密度值呈升高趋势。实验 2 采用替代的 PTH 抑制方法，结果与实验 1 相似。
结论
这些数据表明，基于 PTH 抑制的干预措施可使 CKD 中的皮质骨灌注正常化。
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