Endocrine Abstracts

Introduction: Osteoporosis is a multifactorial disease characterized by reduced bone mass and increased risk of fragility fractures. Menopause predisposes women to osteoporosis due to declining estrogen levels. Iron is known to play a relevant role in the development of osteoporosis since iron suppresses osteoblast formation and may also stimulate osteoclast resorption of bone. Also, homocysteine is a known risk factor for osteoporotic fractures and is related to DNA methylation, suggesting that polymorphisms in genes affecting both can increase susceptibility to the development of osteoporosis.

Objectives: This study aimed to investigate the potential implication of genetic polymorphisms in genes related to iron metabolism and DNA methylation 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 305 Portuguese postmenopausal women, of which 156 had osteoporosis and 149 had normal bone mass. Polymorphic analyses on the HFE (H63D and C282Y) and MTHFR (C677T) genes were performed by PCR-RFLP. The Hp phenotype was determined by polyacrylamide gel electrophoresis. Plasma 17β-estradiol concentration was determined by ELISA. The results were adjusted for age and body mass index. All statistical analyzes were performed using SPSS software, version 24.0.

Results: An association was found between 17β-estradiol and osteoporosis, being a protective effect observed in the presence of higher levels of estradiol [OR (95% CI) = 0.456 (0.215-0.968); P=0.041]. Significant differences were found for the MTHFR gene, with the TT genotype being protective for osteoporosis [OR (95% CI) = 0.283 (0.097-0.823); P=0.021]. Also, women who had the Hp 1 allele and higher levels of estradiol had increased protection for osteoporosis [OR (95% CI) = 0.270 (0.081-0.859); P=0.032], as well as in the presence of the T allele of the C677T polymorphism and higher levels of estradiol [OR (95% CI) = 0.100 (0.026-0.375); P=0.001].

Conclusion: Since these genes are related to iron metabolism and DNA methylation, the results of this study suggest their participation in interaction with estradiol for the development of osteoporosis in postmenopausal women.