Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women

Abstract

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).

Conclusion: 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.