Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women.
OBJECTIVE
To determine whether serum levels of 2 Wnt signaling antagonists, Frizzled-related protein (FRP) and Dkk-1, are associated with the development and progression of radiographic hip osteoarthritis (RHOA).


METHODS
Pelvic radiographs were obtained a mean of 8.3 years apart in 5,928 Caucasian women >or=65 years of age who were enrolled in the Study of Osteoporotic Fractures. Random sampling of this cohort was performed, with approximately 180 subjects per group assigned to 2 nested case-control studies on RHOA incidence and progression. Baseline serum levels of FRP and Dkk-1 were measured by capture enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analyses with adjustment for potential covariates.


RESULTS
There were no differences in serum levels of FRP and Dkk-1 between case subjects with incidence or progression of RHOA and their respective control subjects. There was a trend for higher baseline serum levels of FRP to be associated with a reduced risk of incident RHOA (age-adjusted OR 0.59 [95% CI 0.32-1.09], P = 0.09 for women in the highest quartile versus women in the lowest quartile). There was no association of serum levels of FRP with progression of RHOA. Serum levels of Dkk-1 did not correlate with incident RHOA. However, higher serum levels of Dkk-1 were associated with diminished risk of RHOA progression (age-adjusted OR 0.43 [95% CI 0.23-0.79], P = 0.007 for women in the highest quartile compared with women in the lowest quartile).


CONCLUSIONS
Elevated circulating levels of Dkk-1 appeared to be associated with reduced progression of RHOA in elderly women, whereas the highest quartile of serum FRP levels tended to be associated with a modest reduction in risk of incident RHOA.
Lane
Nancy E
NE
University of California, Davis, Sacramento, CA 95817, USA. nelane@ucdavis.edu
Nevitt
Michael C
MC
Lui
Li-Yung
LY
de Leon
Patricia
P
Corr
Maripat
M
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins; D015207:Osteoarthritis, Hip / Q000097:blood / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis*; D011859:Radiography; D015398:Signal Transduction; D044465:White People; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D000099274:Frizzled-Related Proteins
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins; C501126:DKK1 protein, human