Inhibition of tnf-α reverses the pathological resorption pit profile of osteoclasts from patients with acute charcot osteoarthropathy

We hypothesised that tumour necrosis factor-α (tnf-α) may enhance receptor activator of nuclear factor-β ligand-(rankl-) mediated osteoclastogenesis in acute charcot osteoarthropathy. peripheral blood monocytes were isolated from 10 acute charcot patients,8 diabetic patients,and 9 healthy control subjects and cultured in vitro on plastic and bone discs. osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (m-csf) and rankl and (2) m-csf,rankl,and neutralising antibody to tnf-α (anti-tnf-α). resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. although osteoclast formation was similar in m-csf + rankl-treated cultures between the groups (p>0.05),there was a significant increase in the area of resorption on the surface (p<0.01) and under the surface (p<0.01) in charcot patients compared with diabetic patients and control subjects. the addition of anti-tnf-α resulted in a significant reduction in the area of resorption on the surface (p<0.05) and under the surface (p<0.05) only in charcot patients as well as a normalisation of the aberrant erosion profile. we conclude that tnf-α modulates rankl-mediated osteoclastic resorption in vitro in patients with acute charcot osteoarthropathy. © 2015 nina l. petrova et al.