Osteoporosis in Hemochromatosis: Iron Excess, Gonadal Deficiency, or Other Factors?

Study objective To define the prevalence, severity, type and pathogenesis of osteopenia in idiopathic hemochromatosis. Design Prospective study conducted over 18 months. Setting Tertiary care center. Subjects Twenty-two men with idiopathic hemochromatosis and 20 age-matched controls. There were 5 hypogonadal patients, 9 eugonadal nonvenesected patients, and 8 eugonadal venesected patients. Measurements and main results All patients and controls were evaluated by spinal radiography, spinal and forearm bone mineral density estimations, dynamic skeletal histomorphometry, and serum biochemistry. Ten patients (45%; 95% CI, 24% to 68%) had osteoporosis as defined by spinal and forearm bone density measurements. Trabecular bone volumes were significantly reduced in the patients (the difference in means between patients and age-matched controls was 3.9%; CI, 1.3% to 6.7%). No patient had osteomalacia. Hypogonadal men had lower bone mass measurements than eugonadal men (radial bone density: beta coefficient = -20.5; CI, -29.2 to -11.8; trabecular bone volume: beta coefficient = -7.1; CI, -10.8 to -3.3). Osteoid and osteoblastic surfaces and bone formation rates were significantly greater in the eugonadal venesected compared with the eugonadal nonvenesected persons (P less than 0.05 for all measurements). Conclusions A significant decrease in bone density is seen in idiopathic hemochromatosis, particularly when hypogonadism is present. Low serum free-testosterone concentrations rather than the calciotrophic hormones determine bone mass in this condition.