University of Verona, Rheumatology Unit, Piazzale L. Scuro 10, 37134, Verona, Italy.
Clin Rheumatol. 2018 Nov;37(11):3093-3098. doi: 10.1007/s10067-018-4205-0. Epub 2018 Jul 11.
Available studies reported contradictory results about serum levels Dickkopf-1 (DKK1), an inhibitor of Wnt signaling in patients with ankylosing spondylitis (AS). In previous studies, we observed in other conditions that parathyroid hormone (PTH) serum levels were an important determinant of DKK1 serum levels. The aim of the present study was to investigate it in patients with AS. We recruited 71 patients diagnosed with AS. Levels of C-reactive protein (CRP), DKK1, PTH, 25OH-vitamin D, and bone turnover markers (intact N-propeptide of type I collagen, P1NP, and C-terminal telopeptide of type I collagen, CTX) were measured and compared to healthy controls (HC). Dual X-ray absorptiometry at lumbar spine and proximal femoral site was used for bone mineral density (BMD) assessment and spine X-rays were also performed. PTH serum levels were found to be significantly higher in AS patients than in HC (33.8 ± 14.11 vs 24.8 ± 13 pg/ml, p = 0.002), while mean DKK1 serum levels were lower than in HC (23.3 ± 13.1 vs 29.8 ± 15.9 pmol/l, p = 0.009). A positive correlation between DKK1 and PTH (correlation coefficient + 0.25, p = 0.03) was observed; it remained significant in a multivariate analysis. In patients with longer disease duration, DKK1 was also positively correlated with CTX (coefficient 0.42, p = 0.01), and PTH was higher in those patients with low BMD (Z-score ≤ - 1) at any site (p = 0.04). Also in AS, PTH is an important determinant of DKK1 serum levels and should be evaluated in studies on DKK1. PTH might have a role in bone involvement in AS, also through the Wnt pathway.
现有研究报告称,在强直性脊柱炎(AS)患者中,Dickkopf-1(DKK1)的血清水平(Wnt 信号通路的抑制剂)存在矛盾的结果。在之前的研究中,我们在其他情况下观察到,甲状旁腺激素(PTH)的血清水平是 DKK1 血清水平的一个重要决定因素。本研究的目的是在 AS 患者中对此进行研究。我们招募了 71 名被诊断为 AS 的患者。测量了 C 反应蛋白(CRP)、DKK1、PTH、25OH-维生素 D 和骨转换标志物(I 型胶原 N 端前肽、P1NP 和 I 型胶原 C 端肽、CTX)的水平,并与健康对照组(HC)进行了比较。采用双能 X 线吸收法(DXA)对腰椎和股骨近端进行骨密度(BMD)评估,同时进行脊柱 X 线检查。结果发现,AS 患者的 PTH 血清水平明显高于 HC(33.8±14.11 与 24.8±13pg/ml,p=0.002),而 DKK1 血清水平则低于 HC(23.3±13.1 与 29.8±15.9pmol/l,p=0.009)。观察到 DKK1 与 PTH 之间存在正相关(相关系数+0.25,p=0.03),在多变量分析中仍然具有统计学意义。在疾病持续时间较长的患者中,DKK1 与 CTX 也呈正相关(系数 0.42,p=0.01),并且在任何部位 BMD(Z 评分≤-1)较低的患者中,PTH 水平较高(p=0.04)。在 AS 中,PTH 也是 DKK1 血清水平的一个重要决定因素,应该在 DKK1 的研究中进行评估。PTH 可能通过 Wnt 通路在 AS 的骨骼受累中发挥作用。