Bone and joint involvement in genetic hemochromatosis : role of cirrhosis and iron overload

Objective. To evaluate the frequency of arthropathy and osteoporosis in genetic hemochromatosis (GH) and to quantify potential risk factors for these 2 conditions. Methods. Radiographic evidence of arthropathy was systematically sought in plain radiographs of 32 patients (28 men) with histologically proven GH (17 with hepatic cirrhosis). Bone mineral density was measured by x-ray absorptiometry of L2-L4 and osteoporosis was defined as a T score greater than or equal to 2.5 standard deviation below the mean. Potential risk factors investigated were age, body mass index, cirrhosis, alcohol abuse, hepatitis B and C infections, HLA phenotype, serum free testosterone levels, and the amount of iron removed by phlebotomy to reach depletion. The independent role of risk factors for the presence of osteoporosis was tested by multiple logistic regression analysis. Results. Radiologic signs of arthropathy were observed in 81.3% of cases. Patients with arthropathy were older than patients without (p < 0.001), but did not differ in the frequency of cirrhosis, amount of iron removed, and HLA typing. Osteoporosis was observed in 9 patients and was positively associated with the amount of iron removed and cirrhosis. However, in multivariate analysis, cirrhosis was not independently associated with osteoporosis, but patients with higher iron removed had a greater probability to have osteoporosis [odds ratio (OR) = 3.23 for any increase of 5 g, 95% confidence interval (CI): 1.09-9.58], whereas the presence of HLA-A3 was associated with a reduction of risk (OR 0.013, 95% CI: 0.0015-1.13). Conclusion. These findings indicate the high prevalence of osteoarticular involvement in Italian patients with GH. Neither cirrhosis nor the amount of iron removed was associated with arthropathy. In contrast, in univariate analysis the risk of osteoporosis was significantly increased by liver cirrhosis. With multivariate analysis we found that osteoporosis was highly influenced by the degree of iron overload, playing an independent role in accelerating bone loss in patients with GH.