Endocrine Abstracts

Introduction: Osteoporosis is a common metabolic bone disease characterized by reduced bone mass and increased risk of fragility fractures. The pathogenesis of this disease is complex and influenced by multiple risk factors, where genetic factors play an important role. Menopause predisposes women to osteoporosis due to declining estrogen levels. Osteoporosis and iron metabolism have an important relationship. Iron overload suppresses osteoblast formation and stimulate osteoclast resorption of bone, suggesting that polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis.

Objectives: This study aimed to investigate the potential implication of genetic polymorphisms in genes related to iron metabolism and their interaction with estradiol in the development of osteoporosis in a sample of postmenopausal women.

Material and methods: A case-control study was carried out for a sample of 169 Portuguese postmenopausal women, of which 78 had osteoporosis and 91 had normal bone mass. Polymorphic analyzes on the HFE gene (H63D and C282Y) were performed by PCR-RFLP. The haptoglobin (Hp) phenotype was determined by polyacrylamide gel electrophoresis. Plasma 17β-estradiol concentration was determined by ELISA. All statistical analyzes were performed using SPSS software, version 24.0.

Results: An association was found between lower levels of 17β-estradiol and osteoporosis [OR (95% CI) = 5,946 (2,199-16,079); P<0.001]. When the genes were analyzed separately, no significant differences were found between the two populations in relation to the polymorphisms under study. However, women with the presence of the H allele of the H63D polymorphism of the HFE gene and lower levels of estradiol had an increased risk of developing osteoporosis [OR (95% CI) = 22,750 (2,492-207,731); P=0.001], as well as the presence of the CC genotype of the C282Y polymorphism of the HFE gene and lower levels of estradiol [OR (95% CI) = 11,667 (2,139-63,638); P=0.002]. Also women who had the Hp 2 allele and lower levels of estradiol had an increased risk of developing osteoporosis [OR (95% CI) = 7,023 (1,813-27,200); P=0.005].

Conclusion: Since these genes are related to iron metabolism, the results of this study suggest an action of this metabolism in interaction with estradiol levels in the development of osteoporosis in postmenopausal women.