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Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand.

Abstract：

AIMS/HYPOTHESIS:Our aims were to compare osteoclastic activity between patients with acute Charcot's osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). METHODS:Peripheral blood monocytes isolated from nine diabetic Charcot patients, eight diabetic control and eight healthy control participants were cultured in the presence of macrophage-colony stimulating factor (M-CSF) alone, M-CSF and RANKL, and also M-CSF and RANKL with excess concentrations of OPG. Osteoclast formation was assessed by expression of tartrate-resistant acid phosphatase on glass coverslips and resorption on dentine slices. RESULTS:In cultures with M-CSF, there was a significant increase in osteoclast formation in Charcot patients compared with healthy and diabetic control participants (p=0.008). A significant increase in bone resorption was also seen in the former, compared with healthy and diabetic control participants (p<0.0001). The addition of RANKL to the cultures with M-CSF led to marked increase in osteoclastic resorption in Charcot (from 0.264+/-0.06% to 41.6+/-8.1%, p<0.0001) and diabetic control (0.000+/-0.00% to 14.2+/-16.5%, p<0.0001) patients, and also in healthy control participants (0.004+/-0.01% to 10.5+/-1.9%, p<0.0001). Although the addition of OPG to cultures with M-CSF and RANKL led to a marked reduction of resorption in Charcot patients (41.6+/-8.1% to 5.9+/-2.4%, p=0.001), this suppression was not as complete as in diabetic control patients (14.2+/-16.5% to 0.45+/-0.31%, p=0.001) and in healthy control participants (from 10.5+/-1.9% to 0.00+/-0.00%, p<0.0001). CONCLUSIONS/INTERPRETATION:These results indicate that RANKL-mediated osteoclastic resorption occurs in acute Charcot's osteoarthropathy. However, the incomplete inhibition of RANKL after addition of OPG also suggests the existence of a RANKL-independent pathway.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Mabilleau G,Petrova NL,Edmonds ME,Sabokbar A

doi

10.1007/s00125-008-0992-1

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

1035-40

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

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Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand.