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

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). Me...

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Bibliographic Details
Published in:Diabetologia 2008-06, Vol.51 (6), p.1035-1040
Main Authors: Mabilleau, G, Petrova, N. L, Edmonds, M. E, Sabokbar, A
Format: Article
Language:English
Subjects:
Biological and medical sciences
Charcot's osteoarthropathy
Diabetes
Diabetes. Impaired glucose tolerance
Diseases of the osteoarticular system
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Foot diseases
Human Physiology
Internal Medicine
Life Sciences
Ligands
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Miscellaneous. Osteoarticular involvement in other diseases
OPG
osteoclasts
Osteolysis
Pathogenesis
Phosphatase
RANKL
resorption
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Summary: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.
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-008-0992-1