Malyszko J, Malyszko J S, Wolczynski S, Mysliwiec M
Department of Nephrology and Transplantology, Medical University of Bialystok, Bialystok, Poland.
Transplant Proc. 2003 Sep;35(6):2227-9. doi: 10.1016/s0041-1345(03)00755-3.
Osteoprotegerin (OPG), a natural decoy receptor for osteoclast differentiation factor, is produced by osteoblasts in response to PTH. OPG and its ligand RANKL constitute a complex mediator system involved in the regulation of bone resorption, probably playing an important role in the homeostasis of bone turnover. At present, little is known about the effects of OPG on uremic bone. Successful kidney transplantation reverses many abnormalities of bone metabolism; however, the improvement is often incomplete. The aim of the study was to assess OPG and RANKL concentrations in long-term kidney allograft recipients and their correlations with biochemical markers of bone resorption and formation. The present studies on 48 kidney transplant recipients and 25 healthy volunteers included concentrations of parathormone, osteocalcin, bone-specific alkaline phosphatase, serum CrossLaps, calcidiol, calcitriol, ICTP, PICP, tartrate-resistant acid phosphatase, beta2 microglobulin, IGF-1, IFGBP-1, IGFBP-3, OPG, and RANKL using commercially available kits for measurements. Among kidney transplant recipients OPG and RANKL did not differ between transplant patients and healthy volunteers, whereas other markers of bone formation and resorption were significantly higher in the former group. OPD was related to age, time on dialysis prior transplantation, urea, platelet count, CSA dose, azathioprine dose, 25(OH)D(3), TRAP, IGF-1, IGFBP-3, whereas RANKL was related to leukocyte count, CSA concentration and dose, urine DPD, and beta2 microglobulin content. In healthy volunteers OPG correlated only with CrossLaps, whereas RANKL correlated only with osteocalcin and TRAP. Correlations between OPG, IGF system components, and some markers of bone metabolism may indicate the role of OPG/RANKL system in the pathogenesis of bone metabolism disturbances following renal transplantation.
骨保护素(OPG)是破骨细胞分化因子的天然诱饵受体,由成骨细胞在甲状旁腺激素(PTH)作用下产生。OPG及其配体核因子κB受体活化因子配体(RANKL)构成一个参与骨吸收调节的复杂介质系统,可能在骨转换稳态中发挥重要作用。目前,关于OPG对尿毒症骨的影响知之甚少。成功的肾移植可逆转许多骨代谢异常;然而,改善往往并不完全。本研究的目的是评估长期肾移植受者中OPG和RANKL的浓度及其与骨吸收和形成生化标志物的相关性。本研究对48例肾移植受者和25名健康志愿者进行了检测,使用市售试剂盒测定了甲状旁腺激素、骨钙素、骨特异性碱性磷酸酶、血清I型胶原交联羧基末端肽(CrossLaps)、骨化二醇、骨化三醇、I型胶原羧基末端肽(ICTP)、I型前胶原氨基端前肽(PICP)、抗酒石酸酸性磷酸酶、β2微球蛋白、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IFGBP-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)、OPG和RANKL的浓度。在肾移植受者中,移植患者和健康志愿者之间的OPG和RANKL无差异,而前一组中其他骨形成和吸收标志物明显更高。OPG与年龄、移植前透析时间、尿素、血小板计数、环孢素A(CSA)剂量、硫唑嘌呤剂量、25(OH)D(3)、抗酒石酸酸性磷酸酶(TRAP)、IGF-1、IGFBP-3相关,而RANKL与白细胞计数、CSA浓度和剂量、尿脱氧吡啶啉(DPD)和β2微球蛋白含量相关。在健康志愿者中,OPG仅与CrossLaps相关,而RANKL仅与骨钙素和TRAP相关。OPG、IGF系统成分与一些骨代谢标志物之间的相关性可能表明OPG/RANKL系统在肾移植后骨代谢紊乱发病机制中的作用。