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

Abstract

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 fore-arm 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 < 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.