Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis.

OBJECTIVE: Bone resorption of distal phalanges, or acroosteolysis (AO), can develop in patients with systemic sclerosis (SSc), causing pain and functional limitation. This study was undertaken to investigate 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 AO and 15 without AO) and 14 healthy controls were cultured in the presence of RANKL and macrophage colony-stimulating factor for 9 days. Tartrate-resistant acid phosphatase-positive multinucleated giant cells (MGCs) containing 3 or more nuclei were counted as osteoclasts. Plasma levels and effects of vascular endothelial growth factor (VEGF) on osteoclast formation were evaluated. RESULTS: SSc patients with AO formed significantly more osteoclasts after 9 days than did patients without AO (mean ± SD 142.4 ± 67.0 versus 27.2 ± 17.6 MGCs/well; P < 0.001) or healthy controls (mean ± SD 18.7 ± 27.0 MGCs/well; P < 0.001). No significant difference in osteoclast formation was noted between the patients without AO and healthy controls. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (mean ± SD 142.4 ± 69.6 pg/ml versus 88.1 ± 38.2 pg/ml; P < 0.005) or healthy controls (54.2 ± 24.6 pg/ml; P = 0.018). Priming with VEGF-A for 24 hours significantly increased osteoclast generation by 5.3 ± 1.9 fold (P = 0.0018). The radiographic extent of AO was associated with increased osteoclast formation (Spearman's ρ = 0.741, P = 0.01). CONCLUSION: Our findings indicate that increased osteoclast 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-associated AO.