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. 2020 Jun 18;10(1):9882.
doi: 10.1038/s41598-020-66945-3.

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

Hiroe Sato  1   2 , Chinatsu Takai  3 , Junichiro James Kazama  4 , Ayako Wakamatsu  5 , Eriko Hasegawa  5 , Daisuke Kobayashi  5 , Naoki Kondo  6 , Takeshi Nakatsue  5 , Asami Abe  3 , Satoshi Ito  3 , Hajime Ishikawa  3 , Takeshi Kuroda  7 , Yoshiki Suzuki  7 , Ichiei Narita  5
Affiliations

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

Hiroe Sato et al. Sci Rep. .

Abstract

Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Distributions of serum hepcidin, FGF23, and 25(OH)D levels. As serum hepcidin levels were not normally distributed, the actual hepcidin level + 1 was logarithmically transformed.
Figure 2
Figure 2
Scatter plots of iron metabolism and osteoporosis markers.
Figure 3
Figure 3
Relationships among serum hepcidin, FGF23, and 25(OH)D levels. Each factor was divided into four groups (Q1–Q4), and distributions of other factors are indicated in relation to each quartile.
Figure 4
Figure 4
Estimated relationships related to hepcidin in patients with RA. Hepcidin is usually regulated by iron metabolism—iron overload (black arrow) leads to an increase in hepcidin, and iron deficiency (white arrow) leads to a decrease—and is suppressed by erythropoiesis, sex hormones, and growth factors. To maintain iron homeostasis, higher hepcidin levels result in a decrease in serum iron levels, while lower hepcidin levels increase serum iron levels. When inflammation due to RA occurs, production of hepcidin is increased through inflammatory cytokines that cause elevated ferritin levels. In this study, serum iron levels are positively related to serum hepcidin and ferritin levels but negatively related to inflammation due to RA. This unexpected relationship may give arisen because inflammation in most of the patients was well-controlled. Although iron overload and hepcidin may influence osteoporosis, in this study serum iron level was positively related to BMD but serum hepcidin level was not. However, serum 25(OH)D level was positively related to the serum hepcidin level and also positively related to the femoral Z score in this study. According to previous reports, opposite effects of serum iron level on BMD and 25(OH)D on hepcidin are indicated, and further research is needed to determine the mechanism. Serum FGF23 is not directly related to the serum hepcidin level, but serum 25(OH)D level and inflammation are common factors involved in the regulation of both serum hepcidin and FGF23 levels.
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References

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