title: Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jin Kyun
authors.initials: JK
authors.lastname: Park
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fava
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Carrino
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, and Ospedale Regionale di Lugano, Lugano, Switzerland.
authors.forename: Filippo
authors.initials: F
authors.lastname: Del Grande
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Boin
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D030981:Acro-Osteolysis / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D000328:Adult; D000368:Aged; D001862:Bone Resorption / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D050278:Finger Phalanges / Q000000981:diagnostic imaging*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand; D011859:Radiography; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D000071681:Tartrate-Resistant Acid Phosphatase; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D007527:Isoenzymes; D053245:RANK Ligand; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase