Background/Purpose: Sex has received limited attention in osteoarthritis (OA) clinical studies assessing relationships between biomarkers and pain. In prior work we reported sex-specific associations between knee pain and systemic inflammatory biomarkers. The current study investigated associations with knee synovial fluid (SF) biomarkers, focusing on whether associations differed by sex.

Methods: Patients (n=180) with knee OA scheduled for total joint arthroplasty at a tertiary care hospital in Toronto, Canada. Eligibility: 35+ years of age. Exclusions: acute trauma/injury or inflammatory arthritis. Health questionnaires and blood draws were completed in-clinic and knee SF drawn prior to surgical incision. Questionnaire data included knee pain (WOMAC subscale), sex, age, height and weight (BMI was calculated), comorbidity, and symptomatic joints. SF (and blood) biomarker analyses included leptin (adipokine), IL-8 (pro-inflammatory cytokine) and MMP-1 and -2 (matrix metalloproteinases) using Luminex bead-based ELISA assays. Concentration values were log-transformed for analyses. Two linear regression models were estimated (dependent variable: knee pain score). The first included each of the SF biomarkers, adjusted for sex, age, BMI, comorbidity and symptomatic joint count. The second added interaction terms between sex and factors found to have sex-specific influences.

Results: Mean age of the sample was 64 years (range 43-89), 56.2% were female. Females had higher comorbidity and joint counts, and worse knee pain scores than males. Median marker concentrations for leptin and MMP-1 were higher in females. No difference was found for IL-8 and MMP-2. In adjusted analyses, initially without sex-specific consideration, none of the biomarkers were associated with pain scores. When sex-specific effects were assessed, all biomarkers were significantly associated with pain, but differently for males and females. The association between leptin and pain was positive in males, negative in females (p=0.004). For IL-8, a negative association was found in males (p=0.022) but none in females. For MMP-2, a negative association was found only in females (p=0.008). Finally, MMP-1 was similarly positively associated with pain in males and females. Sensitivity analyses: additional adjustment for corresponding systemic biomarkers showed a positive association between systemic IL-8 and pain in males and negative association in females (p=0.002); SF biomarker associations were unchanged.

Conclusion: Findings provide evidence of sex-specific associations between SF biomarkers and knee OA pain, suggesting drug targets for OA symptom management may need to be sex-specific. They further highlight that sex considerations in OA clinical/epidemiological studies are essential.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/sex-specific-associations-between-knee-synovial-fluid-biomarkers-and-knee-osteoarthritis-pain/