Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis.
OBJECTIVE
Recent reports have suggested that increasing adiposity may protect against radiographic damage in rheumatoid arthritis (RA). We explored the role of serum adipokines (adiponectin, resistin, and leptin) in mediating this association.


METHODS
Patients with RA underwent total-body dual x-ray absorptiometry for measurement of total and regional body fat and lean mass, abdominal computed tomography for measurement of visceral fat area, and radiographs of the hands and feet scored according to the modified Sharp/van der Heijde (SHS) method. Serum levels of adipokines were measured and cross-sectional associations with radiographic damage were explored, adjusting for pertinent confounders. The associations of measures of adiposity with radiographic damage were explored with the introduction of adipokines into multivariable modeling as potential mediators.


RESULTS
Among the 197 patients studied, adiponectin demonstrated a strong association with radiographic damage, with the log SHS score increasing by 0.40 units for each log unit increase in adiponectin (P = 0.001) after adjusting for pertinent predictors of radiographic damage. Adiponectin independently accounted for 6.1% of the explainable variability in SHS score, a proportion comparable with rheumatoid factor, and greater than HLA-DRB1 shared epitope alleles or C-reactive protein levels. Resistin and leptin were not associated with radiographic damage in adjusted models. An inverse association between visceral fat area and radiographic damage was attenuated when adiponectin was modeled as a mediator. The association of adiponectin with radiographic damage was stronger in patients with longer disease duration.


CONCLUSIONS
Adiponectin may represent a mechanistic link between low adiposity and increased radiographic damage in RA. Adiponectin modulation may represent a novel strategy for attenuating articular damage.
Giles
Jon T
JT
The Johns Hopkins University School of Medicine, Baltimore, Maryland. gilesjont@jhmi.edu
Allison
Matthew
M
Bingham
Clifton O
CO
Scott
William M
WM
Bathon
Joan M
JM
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood*; D050154:Adiposity / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D050152:Intra-Abdominal Fat / Q000503:physiopathology; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D052243:Resistin / Q000097:blood; D012720:Severity of Illness Index
D052242:Adiponectin; D020738:Leptin; D052243:Resistin