Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
Guttmann Neurorehabilitation Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
J Bone Miner Res. 2015 Jun;30(6):1014-21. doi: 10.1002/jbmr.2423.
Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short-term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk-1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty-two patients (aged 35 ± 14yrs) with a recent (<6months) complete SCI were prospectively included. Sclerostin and Dkk-1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12-month follow-up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow-up. Additionally, they presented significantly increased Dkk-1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (-20.2 ± 5.4%, p < 0.01), total body (-5.7 ± 2.2%, p = 0.02) and lower extremities (-13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk-1 values (>58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short-term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk-1 serum levels. The persistence of increased levels of this Wnt antagonist throughout the study and their relationship with the magnitude of bone loss suggests a contributory role of this mediator in this process.
脊髓损伤 (SCI) 与骨丢失和骨重塑显著增加有关，尤其是在损伤后短期。骨细胞机械感觉功能介导的机械负荷缺失似乎是与这种情况下骨丢失相关的一个致病因素。然而，这一过程的发病机制和临床管理仍不清楚。因此，本研究旨在分析近期 SCI 对 Wnt 通路拮抗剂骨硬化蛋白和 Dickkopf（Dkk-1）的影响，以及它们与骨转换和骨密度（BMD）演变的关系。42 名近期（<6 个月）完全性 SCI 患者前瞻性纳入本研究。在基线和 6 个月和 12 个月时评估骨硬化蛋白和 Dkk-1、骨转换标志物（骨形成：PINP、骨 ALP；吸收：sCTx）和 BMD（腰椎、股骨近端、全身和下肢[DXA]）。结果与健康对照组进行比较。22/42 名患者完成了 12 个月的随访。基线时，SCI 患者的骨标志物（PINP 和 sCTx）明显增加，随访至 6 个月时仍明显增加。此外，他们在整个研究过程中 Dkk-1 值显著升高，而骨硬化蛋白值没有显著变化。BMD 在股骨近端（-20.2±5.4%，p<0.01）、全身（-5.7±2.2%，p=0.02）和下肢（-13.1±4.5%，p=0.01）在 12 个月时明显下降。因此，59%的患者在 12 个月时发展为骨密度骨质疏松症。基线时 Dkk-1 值较高（>58pmol/L）的患者亚部位 BMD 丢失较高。总之，本研究表明，SCI 后短期会出现明显的骨转换和骨丢失增加，后者与 Dkk-1 血清水平升高有关。这种 Wnt 拮抗剂在整个研究过程中持续升高及其与骨丢失程度的关系表明，该介质在这一过程中起促进作用。
