BONE AND JOINT INVOLVEMENT IN GENETIC HEMOCHROMATOSIS - ROLE OF CIRRHOSIS AND IRON OVERLOAD

Objective. To evaluate the frequency of arthropathy and osteoporosis i n 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 miner al density was measured by x-ray absorptiometry of L2-L4 and osteoporo sis was defined as a T score greater than or equal to 2.5 standard dev iation below the mean. Potential risk factors investigated were age, b ody mass index, cirrhosis, alcohol abuse, hepatitis B and C infections , HLA phenotype, serum free testosterone levels, and the amount of iro n removed by phlebotomy to reach depletion. The independent role of ri sk factors for the presence of osteoporosis was tested by multiple log istic regression analysis.Results. Radiologic signs of arthropathy wer e observed in 81.3% of cases. Patients with arthropathy were older tha n patients without (p < 0.001), but did not differ in the frequency of cirrhosis, amount of iron removed, and HLA typing. Osteoporosis was o bserved in 9 patients and was positively associated with the amount of iron removed and cirrhosis. However, in multivariate analysis, cirrho sis was not independently associated with osteoporosis, but patients w ith higher iron removed had a greater probability to have osteoporosis [odds ratio (OR) = 3.23 for any increase of 5 g, 95% confidence inter val (CI): 1.09-9.58], whereas the presence of HLA-A3 was associated wi th a reduction of risk (OR 0.013, 95% CI: 0.0015-1.13). Conclusion. Th ese findings indicate the high prevalence of osteoarticular involvemen t in Italian patients with GH. Neither cirrhosis nor the amount of iro n 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 independe nt role in accelerating bone loss in patients with GH.