Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida - Dr. Pifarré Foundation (IRBLleida), Lleida, Spain.
Calcium Metabolism and Vascular Calcification Unit, Maimonides Institute for Biomedical Research (IMIBIC), Cordoba, Spain.
FASEB J. 2024 Jun 15;38(11):e23726. doi: 10.1096/fj.202302704R.
Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.
骨化三醇和钙敏感受体激动剂用于治疗慢性肾脏病（CKD）继发的甲状旁腺功能亢进症。骨化三醇的应用和随后血清钙浓度的增加会降低甲状旁腺激素（PTH）水平，这应该会减少骨重塑。我们之前曾报道过，在维持 PTH 浓度不变的情况下，添加钙敏感受体激动剂会增加骨细胞的活性。骨化三醇的应用是否会在维持 PTH 浓度不变的情况下影响骨细胞的活性，应在肾性骨营养不良的动物模型中进行评估。本研究的目的是在 CKD PTH 钳夹大鼠中比较骨化三醇和钙敏感受体激动剂的骨骼作用。结果表明，在 5/6 肾切除术（Nx）继发性甲状旁腺功能亢进大鼠和 PTH 钳夹 Nx 大鼠中，以相似的 PTH 分泌减少剂量给予骨化三醇和钙敏感受体激动剂，对成骨细胞活性产生了不同的影响。值得注意的是，在这两种大鼠模型中，骨化三醇的应用均降低了成骨细胞的活性，而钙敏感受体激动剂则增加了骨细胞的活性。在体外，骨化三醇补充剂抑制了β-连环蛋白的核易位，并减少了向成骨细胞分化的间充质干细胞的增殖、成骨和矿化。总之，除了骨化三醇和钙敏感受体激动剂在甲状旁腺水平的作用外，这些治疗方法对骨细胞具有特定的作用，与 PTH 水平无关。
