Valenzuela Antonia, Pérez Guillermo, Chung Lorinda, Sánchez Felipe, Iturriaga Carolina, Montalva Rebeca, Borzutzky Arturo
Pontificia Universidad Católica de Chile, Santiago, Chile.
Stanford University School of Medicine, Palo Alto, California.
ACR Open Rheumatol. 2025 Apr;7(4):e70029. doi: 10.1002/acr2.70029.
We aimed to assess whether the presence of radiographically confirmed calcinosis of the hands in patients with systemic sclerosis (SSc) is associated with increased osteoclastogenesis.
We recruited 20 patients with SSc (10 with calcinosis and 10 without calcinosis) and 10 age- and gender-matched healthy controls. Hand radiographs were scored using the validated Scleroderma Clinical Trials Consortium (SCTC) radiographic severity score for calcinosis. To evaluate osteoclastogenesis, peripheral blood mononuclear cells (PBMCs) were cultured with RANKL and macrophage colony-stimulating factor; osteoclasts were identified using tartrate-resistant acid phosphatase staining. Measures of bone resorption (RANKL, osteoprotegerin [OPG]) and ischemia or endothelial function (vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 [Ang-2]) were also evaluated.
Patients with SSc were all women and Hispanic, and the majority (n = 12, 60%) had limited SSc skin type. Mean ± SD age was 55.2 ± 14.8 years; mean ± SD disease duration was 9.5 ± 6.5 years from first non-Raynaud phenomenon symptom. Patients with SSc with calcinosis had more digital ischemia than patients without calcinosis. Median SCTC score in patients with SSc with calcinosis was 11.1 (range 0.7-286). After 9 days in culture, PBMCs from patients with calcinosis originated a significantly higher number of osteoclasts (33.0 ± 20.3 cells/well) than patients without calcinosis (15.3 ± 6.9 cells/well) and healthy individuals (11.2 ± 2.6 cells/well) (P = 0.001). The severity of calcinosis was not correlated with the number of osteoclasts per well (r = 0.27, P = 0.5); however, it was correlated with RANKL (r = 0.82, P = 0.004), RANKL/OPG ratio (r = 0.86, P = 0.002), and Ang-2 levels (r = 0.86, P = 0.002).
Calcinosis in patients with SSc is associated with an increased propensity of peripheral blood cells to form osteoclasts. Targeted inhibition of osteoclastogenesis may provide a specific therapeutic option for patients with SSc-associated calcinosis.
我们旨在评估系统性硬化症（SSc）患者手部经影像学证实的钙质沉着症是否与破骨细胞生成增加有关。
我们招募了20例SSc患者（10例有钙质沉着症，10例无钙质沉着症）以及10例年龄和性别匹配的健康对照者。使用经过验证的硬皮病临床试验联盟（SCTC）钙质沉着症影像学严重程度评分对手部X光片进行评分。为评估破骨细胞生成，将外周血单个核细胞（PBMCs）与核因子κB受体活化因子配体（RANKL）和巨噬细胞集落刺激因子一起培养；使用抗酒石酸酸性磷酸酶染色鉴定破骨细胞。还评估了骨吸收指标（RANKL、骨保护素[OPG]）以及缺血或内皮功能指标（血管内皮生长因子、血管生成素-1和血管生成素-2[Ang-2]）。
SSc患者均为女性且为西班牙裔，大多数（n = 12，60%）为局限性皮肤型SSc。平均±标准差年龄为55.2±14.8岁；从首次出现非雷诺现象症状起，平均±标准差病程为9.5±6.5年。有钙质沉着症的SSc患者比无钙质沉着症的患者有更多的指端缺血。有钙质沉着症的SSc患者的SCTC评分中位数为11.1（范围0.7 - 286）。培养9天后，有钙质沉着症患者的PBMCs产生的破骨细胞数量（33.0±20.3个/孔）显著高于无钙质沉着症患者（15.3±6.9个/孔）和健康个体（11.2±2.6个/孔）（P = 0.001）。钙质沉着症的严重程度与每孔破骨细胞数量无关（r = 0.27，P = 0.5）；然而，它与RANKL（r = 0.82，P = 0.004）、RANKL/OPG比值（r = 0.86，P = 0.002）以及Ang-2水平（r = 0.86，P = 0.002）相关。
SSc患者的钙质沉着症与外周血细胞形成破骨细胞的倾向增加有关。针对性抑制破骨细胞生成可能为SSc相关钙质沉着症患者提供一种特异性治疗选择。
