Reduced hepcidin level features osteoporosis

Abstract

Osteoporosis (OP) is a common serious skeletal disorder marked by increased risk of bone fracture due to fragility. OP has been taken to be a disease linked with abnormal calcium metabolism that alone is obviously insufficient to explain the development of OP. Iron overload has been associated with the development of OP and increasing studies have suggested the association. However, direct evidence for this has not been clinically established. To this end, using the Roche biochemical autoanalyzer, we detected the concentration of iron, soluble transferrin receptor 2 (TFR2), and hepcidin, a key peptide regulating iron homeostasis, in the sera from patients with OP. It was shown that the iron and TFR2 concentration was markedly higher than that of healthy control; whereas the concentration of hepcidin was markedly lower than that in control. In addition, to pilot explore the underlying mechanism by which hepcidin was downregulated, we present that hepcidin can directly interact with TFR2 using immunoprecipitation. The present study first established the direct biochemical evidence for the involvement of hepcidin in the pathogenesis of OP, indicating that the upregulation of hepcidin could be used as a novel alternative therapeutic strategy in the management of OP.

Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthritis

“…Iron overload (an elevated ferritin level) is a risk factor for progressive bone loss in healthy postmenopausal women and middle-aged men and a risk factor for radiological vertebral fracture in postmenopausal women 13 . Liu et al compared serum hepcidin levels in 40 patients with osteoporosis and 40 healthy controls 14 . They identified lower serum hepcidin levels and higher iron levels in patients with osteoporosis compared to healthy controls, and the serum hepcidin level was negatively related to the serum iron level 14 .…”

“…Liu et al compared serum hepcidin levels in 40 patients with osteoporosis and 40 healthy controls 14 . They identified lower serum hepcidin levels and higher iron levels in patients with osteoporosis compared to healthy controls, and the serum hepcidin level was negatively related to the serum iron level 14 . In this study, the serum hepcidin level was positively related to serum iron and ferritin levels, and serum iron levels were positively related to BMD, in contrast to the studies outlined above.…”

“…Iron overload is a risk factor for progressive bone loss in healthy postmenopausal women and middle-aged men 13 . Furthermore, in one study, lower serum hepcidin levels and higher serum iron levels were reported in patients with osteoporosis than healthy controls 14 .…”

Screening of superior anti‐osteoporotic flavonoids from Epimedii Folium with dual effects of reversing iron overload and promoting osteogenesis

“…Decreased estrogen levels in postmenopausal women lead not only to the imbalance of bone metabolism but also to increased LPI, which becomes a dual risk factor for PMOP. Current clinical evidence showed that PMOP patients tend to have iron overload symptoms including decreased hepcidin levels (Liu et al, 2018) and high serum ferritin levels (Cheng et al, 2017), which in turn exacerbate bone loss. Epimedii Folium is an effective Chinese herb used for thousands of years to treat orthopedic diseases.…”

Iron Metabolism: From Inflammation to Cancer

“…Hepcidin knockout mice had a higher serum ferritin level and higher iron in the liver than controls and showed low bone mass and changes in bone microarchitecture [99]. Liu et al compared serum hepcidin levels in 40 patients with OP and 40 healthy controls demonstrating lower serum hepcidin levels and higher iron levels in patients with OP and that the serum hepcidin level was negatively related to the serum iron level [100]. In contrast, Sato et al demonstrated that the serum hepcidin level was positively related to serum iron and ferritin levels, and serum iron levels were positively related to BMD [99].…”