Cytokine-induced osteoclastic bone resorption in charcot arthropathy: an immunohistochemical study.
BACKGROUND
Charcot arthropathy is a chronic, progressive destructive process affecting bone architecture and joint alignment in people lacking protective sensation. The etiologic factors leading to progressive bone resorption have not been elucidated. The purpose of this study was to histologically examine surgical specimens with Charcot arthropathy for cell type and immunoreactivity of known cytokine mediators of bone resorption.


METHODS
Tissue samples of 20 specimens with known Charcot arthropathy were stained for Hematoxylin and Eosin (H&E) to quantify cell type. Nine of the specimens were stained with interleukin-1 (IL-1) antibody, nine with tumor necrosis factor (TNF) alpha antibody, and nine with interleukin-6 (IL-6) antibody. Distribution of staining was graded as focal (less than 10% of cells), moderate (10% to 50% of cells), and diffuse (more than 50% of cells) by two independent investigators. Inflammatory cells in tissue sections of rheumatoid synovium served as a positive control.


RESULTS
Osteoclasts were seen in excessive numbers lining the resorptive bone lacunae. There was a disproportionate increase in osteoclasts to osteoblasts in the Charcot-reactive bone. In each case, osteoclasts demonstrated immunoreactivity for IL-1, IL-6 and TNF-alpha with a grade of moderate or diffuse reactivity.


CONCLUSIONS
The findings of excessive osteoclastic activity in the environment of cytokine mediators of bone resorption (IL-1, IL-6, and TNF-alpha) suggest enhanced bone resorption through the stimulation of osteoclastic progenitor cells as well as mature osteoclasts. Alteration in the synthesis, secretion, or activity of these important regulatory molecules through the use of pharmacologic agents may, in turn, alter bone remodeling and loss and lead to accelerated healing without collapse or malalignment.
Baumhauer
Judith F
JF
Department of Orthopaedics, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA. judy_baumhauer@urmc.rochester.ed
O'Keefe
Regis J
RJ
Schon
Lew C
LC
Pinzur
Michael S
MS
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000473:pathology; D001177:Arthropathy, Neurogenic / Q000276:immunology / Q000473:pathology*; D001862:Bone Resorption / Q000276:immunology / Q000473:pathology*; D004396:Coloring Agents; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004396:Coloring Agents; D016207:Cytokines; D005456:Fluorescent Dyes; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha