Compared to wild-type mice, IRP2−/− mice showed obvious symptoms of osteoporosis, such as decreased bone mineral density and bone iron deficiency.115 The levels of bone formation markers in serum, including bone-gla-protein and type I collagen, were decreased, whereas those of bone resorption markers, such as tartrate-resistant acid phosphatase and cathepsin K, were significantly elevated.115 In the bone tissue of IRP2−/− mice, the expression of ferritin and FPN was reduced, while TFR1 expression was elevated, suggesting that iron disorders in bones may lead to osteoporosis. This evidence concerns the gene IREB2 and iron metabolism disease.