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

• Published in: Arthritis and rheumatism Vol. 56; no. 10; pp. 3319 - 3325
• Main Authors: Lane, Nancy E., Nevitt, Michael C., Lui, Li‐Yung, de Leon, Patricia, Corr, Maripat
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007; Wiley
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; Disease Progression; Diseases of the osteoarticular system; Enzyme-Linked Immunosorbent Assay; European Continental Ancestry Group; Female; Humans; Intercellular Signaling Peptides and Proteins - blood; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; Osteoarthritis; Osteoarthritis, Hip - blood; Osteoarthritis, Hip - diagnostic imaging; Osteoporosis. Osteomalacia. Paget disease; Predictive Value of Tests; Prognosis; Prospective Studies; Proteins - analysis; Radiography; Signal Transduction; Wnt Proteins - antagonists & inhibitors; Human; Prognosis; Radiodiagnosis; Diseases of the osteoarticular system; Biological marker; Exploration; Fracture; Epidemiology; Trauma; Hip; Incidence; Radiography; Osteoporosis; Arthropathy; Evolution; Hip osteoarthritis; Degenerative disease; Antagonist; Woman; Osteoarthritis; Elderly; ELISA assay
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.22867

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 ≥65 years of age who were enrolled in the Study of Osteoporotic Fractures. Random sampling of this cohort was performed, with ∼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.