IN patients with systemic sclerosis (SSc), the presence of calcinosis cutis, abnormal calcium deposits in the skin, may signal a deeper issue tied to osteoclastogenesis, the formation of bone-resorbing cells, according to a new study. The research found a significant increase in osteoclast activity in patients with SSc and calcinosis, raising important questions about the role of the immune system in both bone metabolism and soft tissue complications.
Researchers analyzed blood samples from 20 Hispanic women with SSc, half of whom had radiographically confirmed calcinosis of the hands, and compared them with healthy controls. When cultured with RANKL and macrophage colony-stimulating factor, peripheral blood mononuclear cells (PBMCs) from patients with calcinosis produced more than double the number of osteoclasts (33.0 ± 20.3 cells/well) compared to those without calcinosis (15.3 ± 6.9) and healthy individuals (11.2 ± 2.6; P = 0.001).
Interestingly, while the severity of calcinosis did not directly correlate with the number of osteoclasts, it strongly correlated with markers of bone resorption and vascular dysfunction, including RANKL (r = 0.82), RANKL/osteoprotegerin ratio (r = 0.86), and Angiopoietin-2 (r = 0.86), all with statistically significant values.
This suggests a biological link between vascular damage, inflammation, and bone metabolism in SSc. The findings could have important implications for treating calcinosis, a notoriously difficult symptom to manage in systemic sclerosis. Researchers propose that targeted inhibition of osteoclastogenesis might offer a more precise therapeutic strategy for these patients.
As treatment options remain limited for SSc-associated calcinosis, this study opens the door for future trials exploring anti-osteoclast agents in this population.
Reference: Valenzuela A et al. Osteoclastogenesis in Patients With Systemic Sclerosis With and Without Calcinosis Cutis. ACR Open Rheumatol. 2025;7(4):e70029.
