Anti-tumor necrosis factor treatment in cherubism - Clinical, radiological and histological findings in two children

作者：Hero M^*; Suomalainen A; Hagstrom J; Stoor P; Kontio R; Alapulli H; Arte S; Toiviainen Salo S; Landenne P; Makitie O

来源：Bone, 2013, 52(1): 347-353.

DOI：10.1016/j.bone.2012.10.003

• Cherubism
• Tumor necrosis factor alpha
• Adalimumab
• SH3-binding protein 2

Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Recent findings in the cherubism mouse model suggest that TNF-alpha plays a major role in disease pathogenesis and that removal of TNF-alpha prevents development of the bone phenotype. %26lt;br%26gt;We treated two children with cherubism with the TNF-alpha antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-alpha staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. %26lt;br%26gt;Based on our findings, TNF-alpha antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-alpha modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.

• 出版日期2013-1