Reducing iron accumulation: A potential approach for the prevention and treatment of postmenopausal osteoporosis

Abstract

Postmenopausal osteoporosis (PMOP) is a systemic bone metabolism disease, characterized by progressive bone loss following menopause and a subsequent increase in fracture risk. Estrogen deficiency as a result of menopause is known to increase bone resorption and accelerate bone loss. Furthermore, postmenopausal women may exhibit iron accumulation, in addition to estrogen deficiency. Elevated iron levels are a risk factor for PMOP in postmenopausal women, and reducing the iron overload has been demonstrated to benefit bone cell metabolism in vitro and improve the bone in vivo by normalizing osteoclastic bone resorption and formation. The identification of hepcidin was a key development in the field of iron metabolism in the previous decade. We hypothesize that hepcidin may aid in the prevention and treatment of PMOP due to its capacity to control body iron stores and its intrinsic effects on osteoblast function. The aim of the current review was to highlight the role of iron accumulation in the pathogenesis of PMOP and to evaluate the possible use of hepcidin as a potential therapy for this condition.

Keywords: hepcidin; iron; osteoporosis; postmenopause.

Figures

Figure 1.

Alterations in the levels of ferritin, E2 and testosterone in women and men over time. (A) Serum levels of E2 were converted to a percentage of the normal value in the serum of 25-year-old women (500 pg/ml). (B) Serum levels of testosterone were converted to a percentage of the normal value in the serum of 20-year-old men (4.4 ng/ml). Levels of ferritin are expressed as ng/ml serum. E2, 17β-estradiol; T, testosterone.

Figure 2.

Hepcidin-ferroportin interaction controls the entry of iron into bone tissues. The rate of iron entry into the bone tissues depends primarily on the serum levels of hepcidin. When serum hepcidin levels are reduced, the ferroportin activity is not blocked effectively. Thus, the release of iron from enterocytes and macrophages increases, resulting in elevated serum iron levels and increased iron deposition in bone tissues.

Figure 3.

Mechanism through which hepcidin stimulates osteoblast differentiation. The binding of hepcidin to ferroportin activates the Jak2 protein kinase, which subsequently results in osteoblast differentiation mediated by the Stat3 transcription factor. Jak2, Janus kinase 2; Stat3, signal transducer and activator of transcription 3.