Bone and joint complications in patients with hereditary hemochromatosis: a cross-sectional study of 93 patients

BACKGROUND: The aim of this study was to determine the frequency and characteristics of bone and joint complications, specifically bone fragility, joint replacement surgery, and arthropathy, in hereditary hemochromatosis (HH) and related factors. METHODS: This study was a cross-sectional observational study of 93 patients with HH. Radiographs of the hands, wrists, knees, and ankles were scored for joint space narrowing, erosions and cysts, osteophytes, and chondrocalcinosis. Prevalent (vertebral and non-vertebral) fragility fractures were recorded and bone mineral density (BMD) was systematically evaluated by dual energy X-ray absorptiometry. Bone fragility was defined as (i) a T-score ⩽ −2.5 at any site with or without a prevalent fragility fracture, or (ii) a T-score between −1.0 and −2.5 at any site and a prevalent fragility fracture. RESULTS: The mean age of the patients was 60.0 (11.2) years, and 58.0% of them were men. The frequency of radiographic MCP2–3 arthropathy was 37.6% (95% CI 0.28–0.48). Radiographic MCP2–3 arthropathy was independently associated with older age [OR 1.17 (1.09–1.26) per year, p < 0.0001], male sex [OR 3.89 (1.17–12.97), p = 0.027] and C282Y+/+ genotype [OR 4.78 (1.46–15.68), p = 0.010]. The frequency of joint replacement surgery was 12.9% (95% CI 0.07–0.21). The frequency of bone fragility was 20.4% (95% CI 0.13–0.30). Bone fragility was independently associated with hepatic cirrhosis [OR 8.20 (1.74–38.68), p = 0.008]. DISCUSSION: Radiographic MCP2–3 arthropathy was found to occur in 37.6% of patients with HH. The association observed between this form of arthropathy and C282Y homozygosity, male sex, and older age suggests that demographic characteristics and genetic background are likely to be major determinants of this joint disorder and play a more important role than severity of iron overload. Bone fragility was observed in a fifth of the patients with HH, independently of genetic background and severity of iron overload, and was strongly associated with hepatic cirrhosis. CONCLUSION: Future investigations should focus on pathogenesis and early identification of patients at risk of developing bone and joint complications secondary to HH.