Association between Iron Intake and Progression of Knee Osteoarthritis

Abstract

Background: Iron overload is drawing attention in the development of knee osteoarthritis (OA). To identify the modifiable risk factors for iron-related pathological conditions, we examined the association between iron intake and the risk of knee OA progression. Methods: A total of 1912 participants in the Osteoarthritis Initiative (OAI), aged 45–79 years and with at least one knee radiographic OA at baseline, were identified and were followed up to 6 years. The iron and other nutrient intake was measured by the validated Block Brief 2000 Food Frequency Questionnaire. The outcome measures were by radiographic progression on the basis of the Kellgren–Lawrence (KL) grade and the joint-space-narrowing (JSN) score. The association between the iron intake and the knee OA progression was examined by Cox proportional hazards models and restricted cubic spline (RCS) regression. Results: Among the study participants, 409 participants experienced KL-grade progression, and 684 participants experienced JSN-score progression within 6 years. Overall, the association between iron intake and the risk of KL-grade progression followed a U shape (p for nonlinearity < 0.001). The risk of KL-grade progression was significantly lower in participants with iron intakes of <16.5 mg/day (per mg/day: adjusted hazard ratio (HR), 0.75; 95% CI (confidence interval), 0.64–0.89), and it was higher in those with iron intakes ≥16.5 mg/day (per mg/day: HR, 1.20; 95% CI, 1.04–1.38). Consistently, when the iron intake was assessed as deciles, compared to those in Deciles 3–5 (10.9–23.3 mg/day), the risk of KL-grade progression was higher for Deciles 1–2 (≤10.9 mg/day: HR, 1.57; 95% CI, 1.17–2.10) and for Deciles 6–10 (>23.3 mg/day: adjusted HR, 1.60; 95% CI, 1.19–2.16). Similar U-shaped relations were found for iron intake with the risk of JSN-score progression (p for nonlinearity = 0.035). Conclusions: There was a U-shaped association between the iron intake and the progression of knee OA, with an inflection point at about 16.5 mg/day, and minimal risk from 10.9 to 23.3 mg/day of iron intake. An appropriate iron intake was advisable for knee OA, whereas excessive or deficient iron intake increased the risk of knee OA progression.