Postmenopausal Iron Overload Exacerbated Bone Loss by Promoting the Degradation of Type I Collagen

Abstract

117 postmenopausal women were divided into Normal, Bone loss (BL), and Osteoporosis group. Compared with Normal group (120.96 ± 43.18 μg/L), the serum ferritin (Fer) in BL (223.37 ± 130.27 μg/L) and Osteoporosis group (307.50 ± 161.48 μg/L) was significantly increased (p < 0.05). Fer level was negatively correlated with BMD (p < 0.01). TRACP levels in Osteoporosis group (4.37 ± 1.69 U/L) were significantly higher than Normal group (4.10 ± 1.60 U/L, p < 0.05). ALP levels in Osteoporosis group (112.06 ± 62.05 U/L) were significantly upregulated compared with Normal group (80.22 ± 14.94 U/L, p < 0.05). β-CTX and PINP were the degradation products of type I collagen. β-CTX levels in Osteoporosis group (667.90 ± 316.55 ng/L) were significantly increased compared with Normal group (406.06 ± 112.12 ng/L, p < 0.05). PINP levels in Osteoporosis group (78.03 ± 37.31 μg/L) were significantly higher than Normal group (37.60 ± 13.17 μg/L, p < 0.01). More importantly, there was a positive correlation between serum Fer and PINP (p < 0.01). Serum Fer showed a positive correlation of serum β-CTX (p < 0.01). The overloaded iron improved the degradation of type I collagen.

Figure 1

Verification of grouping by principal component analysis. First, we grouped according to the T-value of the femur and lumbar vertebrae (Normal T ≥ −1, Bone Loss −2.5 < T < −1, Osteoporosis T ≤ −2.5). Then, the PCA was performed on the data for further verification. Finally, the sample grouping scheme was determined on the basis of the results of the combined PCA and BMD. BMD and PCA were consistent with each other.

Figure 2

Correlative analysis of serum iron on years of menopause and CRP. Fer was positively correlated with years of menopause (p < 0.01). Fer was positively correlated with CRP (p < 0.05). The longer the menopause, the more serious the accumulation of iron, and the inflammatory response is promoted.

Figure 3

Values of serum iron, TRACP, ALP, β-CTX, and PINP in different groups. Compared with the Normal group, the Fer of the Bone Loss group and Osteoporosis group increased significantly (^∗p < 0.05); the TRF of the Osteoporosis group decreased significantly (^∗p < 0.05). TRACP, ALP, β-CTX, and PINP in Osteoporosis group were significantly upregulated by contrast with Normal group (^∗p < 0.05 or ^∗∗p < 0.01). PMOP was associated with iron overload and enhanced bone resorption.

Figure 4

Correlation between serum iron and degradation of type I collagen. There was no correlation between serum iron, ALP, and TRACP. Elevated ALP and TRACP were not caused by iron overload. However, PINP and β-CTX levels were both positively correlated with iron levels (p < 0.01). Iron overload promoted the degradation of type I collagen.

Figure 5

Mechanism of iron overload on PMOP. The overloaded iron improved the degradation of type I collagen and induced inflammatory response. Final performance was height reduction, weight loss, and BMI drop, and BMD decreased very significantly and caused osteoporosis.