Serum iron levels as a risk factor for Osteoporosis-Related pathological fractures
Shangjin Lin1, Xingcai Deng2, Yongqian Fan3
1Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Background:
Osteoporosis is a prevalent bone disease characterized by decreased bone mass and deterioration of bone microstructure, leading to an increased risk of fractures. Pathological fractures, particularly in postmenopausal women, are a severe complication of osteoporosis. This study investigates the potential molecular role of micronutrients, particularly iron, in osteoporosis and its association with pathological fractures.
Methods:
We performed a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the relationship between 15 trace elements (including iron, calcium, copper, and vitamins) and osteoporosis-related outcomes. Outcome data were obtained from the FinnGen database. The inverse-variance weighted (IVW) method was used to evaluate the causal effects of micronutrients on osteoporosis and osteoporosis-related fractures, including those occurring in postmenopausal women. Sensitivity analyses for pleiotropy and heterogeneity, including MR-Egger and leave-one-out analysis, were also performed.
Results:
Among the 15 micronutrients analyzed, serum iron levels were significantly associated with an increased risk of osteoporosis with pathological fractures. The IVW analysis revealed a strong association between iron levels and the occurrence of osteoporosis with pathological fractures (OR = 2.630, 95% CI: 1.161-5.957, P = 0.020), as well as postmenopausal osteoporosis with fractures (OR = 2.714, 95% CI: 1.156-6.368, P = 0.022). No significant genetic association was observed between iron and osteoporosis alone (OR = 1.238, 95% CI: 0.856-1.791, P = 0.256). Other micronutrients did not show significant effects on osteoporosis or fractures. Sensitivity analyses indicated no evidence of heterogeneity or pleiotropy.
Conclusion:
This study identifies serum iron levels as a molecular risk factor for osteoporosis-related pathological fractures, particularly in postmenopausal individuals, but not for osteoporosis itself. These findings highlight the potential role of iron in the pathogenesis of osteoporotic fractures and suggest further investigation into its molecular mechanisms in bone health.
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