Increased risk of arthropathies and joint replacement surgery in patients with genetic hemochromatosis: a study of 3,531 patients and their 11,794 first-degree relatives

Objective: Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (6-20%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs).

Methods: We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression.

Results: Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.14-2.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee replacement (HR 2.14, 95% CI 1.58-2.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities.

Conclusion: Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.