Abstract
BackgroundAge, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role.MethodsIn a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods.ResultsHigher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86–27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023).ConclusionOur data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.
Highlights
Age, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA)
When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin as compared to the male control subjects when dichotomized ferritin was used [Odds ratio (OR) = 4.18, not shown in Table]
In the present study, we have shown for the first time that elevated iron level in the form of serum ferritin resulted in a 4-fold increased risk of developing OA in males, and higher ferritin is associated with narrower joint space width in male patients
Summary
Gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. Osteoarthritis (OA) is the most prevalent joint disease and a major cause of disability and health care burden [1,2]. It is characterized by progressive loss of joint articular cartilage and subchondral bone remodeling [3]. Advanced imaging studies such as MRI reveal changes. Iron is a part of all living cells, and iron increase is associated with age, gender, and gene mutations. A prevalence of 0.5% C282Y homozygotes is estimated among Caucasians, translating to over one million homozygotes in the U.S alone [13,14]
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