Association between Iron Intake and Progression of Knee Osteoarthritis

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.