Acro-osteolysis is associated with enhanced osteoclastogenesis and higher blood VEGF levels in systemic sclerosis

Abstract

Objective

Bone resorption of distal phalanges or acro-osteolysis (AO) can develop in systemic sclerosis (SSc) causing pain and functional limitation. We investigated whether AO may be associated with abnormal osteoclastogenesis in SSc patients and whether hypoxia may be involved in this process.

Methods

Peripheral blood mononuclear cells (PBMCs) obtained from 26 SSc patients (11 with and 15 without AO) and 14 healthy controls (HC) were cultured in the presence of receptor activator of NF-κB-ligand (RANKL) and macrophage colony-stimulating factor for 9 days. Tartrate resistant acid phosphatase (TRAP)+ multinucleated giant cells (MNGs) containing 3 or more nuclei were counted as osteoclasts (OCs). Plasma levels and effects of vascular endothelial growth factor (VEGF) on OC formation were evaluated.

Results

SSc patients with AO formed significantly more OCs after 9 days than did subjects without AO (142.4±67.0 vs. 27.2±17.6 MNGs/well, p<0.001) or HC (18.7±27.0 MNGs/well, p <0.001). No significant difference in OC formation was noted between the patients without AO and HC. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (142.4± 69.6 pg/mL vs. 88.1±38.2 pg/mL, p<0.001) or HC (54.2±24.6 pg/mL, p=0.018). Priming with VEGF-A for 24 hours significantly increased OC generation by 5.3±1.9 fold (p=0.03). The radiographic extent of AO was associated with increased OC formation (Spearman rho=0.741, p=0.01).

Conclusion

Increased OC formation and higher VEGF levels may contribute to AO in SSc patients.Further studies are needed to elucidate whether targeting osteoclastogenesis may provide a specific therapeutic option for SSc-AO.