Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.
graf Biostatistics, Winterthur, Switzerland.
Kidney Blood Press Res. 2020;45(5):758-767. doi: 10.1159/000510565. Epub 2020 Sep 30.
Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients.
Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D.
Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment.
Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.
低骨密度(BMD)是慢性肾脏病(CKD)患者以及肾移植后发生骨折的主要危险因素。然而,目前还没有确定能够可靠预测骨折风险的方法。更好地了解骨转换生物标志物(BTMs)可能有助于填补这一诊断空白。本研究旨在探讨肾移植受者的 BTMs 与 BMD 之间的相关性。
在移植时以及移植后 3 个月测量 BTMs(I 型前胶原 N 端前肽(P1NP)、骨碱性磷酸酶(BSAP)、I 型胶原 C 端肽β异构体和尿脱氧吡啶啉/Cr)的变化,并分别与移植时、6 个月和 12 个月时双能 X 线吸收仪测量的 BMD 变化相关。一半的患者在接受标准钙剂和维生素 D 治疗的基础上加用地舒单抗,每 6 个月皮下注射 2 次。
在未使用地舒单抗的患者中,BSAP 和 P1NP 在 3 个月内的变化与 6 个月内髋部 BMD 的变化呈显著负相关。地舒单抗治疗后,这种相关性消失。
BSAP 和 P1NP 的变化在 BMD 的短期预测中具有一定的应用价值。我们建议进一步的试验,扩大这些 BTMs 的知识,评估骨折风险,在最初的 6 个月内连续测量 BTMs,并额外使用 CT 评估 BMD。