Osteoclastogenesis in Patients With Systemic Sclerosis With and Without Calcinosis Cutis.

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.