Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine (Di.M.I.), Polyclinic San Martino Hospital, University of Genova, Viale Benedetto XV, no. 6, 16132, Genoa, Italy.
Centro di Ricerca su Osteoporosi e Patologie Osteoarticolari CROPO, Di.M.I., University of Genova, Genoa, Italy.
Clin Rheumatol. 2018 Nov;37(11):3057-3062. doi: 10.1007/s10067-018-4322-9. Epub 2018 Oct 6.
The aim of this research was to determine any correlations between Dickkopf-1 serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any difference in Dkk-1 serum levels between SSc and RA patients and a control group (CNT) of healthy subjects. A prospective study was carried out in 60 SSc and 60 RA patients and 60 CNT. Dkk-1 serum levels were evaluated by the ELISA method (Quantikine Human Dkk-1 Immunoassay, R&D System, Minneapolis, USA). The severity of microvascular damage was evaluated by nailfold videocapillaroscopy (NVC patterns: "Early," "Active," "Late"), in the SSc patients. TBS analysis and bone mineral density (BMD, g/cm) were measured in all patients/subjects. The SSc patients showed higher Dkk-1 serum levels than RA (p < 0.004) and CNT (p < 0.0001) patients. SSc patients, showing the "Late" NVC pattern had statistically higher Dkk-1 serum levels than patients with either the "Active" or "Early" (p < 0.004) patterns. Only in the "Late" NVC pattern group of SSc patients was there a significant negative correlation between Dkk-1 and TBS values (p < 0.0001). The increased Dkk-1 serum levels and decreased TBS values observed suggest a diffuse bone damage in SSc patients with advanced disease, as demonstrated by the concomitant presence of the "Late" NVC pattern. Moreover, the bone remodeling in SSc seems even higher than that in RA patients.
本研究旨在确定血清 Dickkopf-1 水平（Dkk-1，一种天然的 Wnt 信号通路抑制剂，可促进破骨细胞生成）与小梁骨评分（TBS）之间的相关性，对象为系统性硬化症（SSc）和类风湿关节炎（RA）患者。还旨在确定 SSc 和 RA 患者与健康对照组（CNT）之间的 Dkk-1 血清水平差异。对 60 例 SSc、60 例 RA 和 60 例 CNT 患者进行了前瞻性研究。采用 ELISA 法（Quantikine 人 Dkk-1 免疫分析试剂盒，美国明尼阿波利斯的 R&D 系统公司）评估 Dkk-1 血清水平。通过甲襞微血管摄像（NVC 模式：“早期”、“活跃”、“晚期”）评估 SSc 患者微血管损伤的严重程度。对所有患者/受试者进行 TBS 分析和骨矿物质密度（BMD，g/cm）测量。SSc 患者的 Dkk-1 血清水平高于 RA（p<0.004）和 CNT（p<0.0001）患者。表现出“晚期”NVC 模式的 SSc 患者的 Dkk-1 血清水平明显高于具有“活跃”或“早期”（p<0.004）模式的患者。只有在 SSc 患者的“晚期”NVC 模式组中，Dkk-1 与 TBS 值之间存在显著负相关（p<0.0001）。观察到的 Dkk-1 血清水平升高和 TBS 值降低表明 SSc 患者存在弥漫性骨损伤，这与“晚期”NVC 模式的同时存在有关。此外，SSc 患者的骨重塑似乎甚至高于 RA 患者。
