Associação entre densidade mineral óssea, polimorfismos do gene da osteoprotegerina, do ligante do Rank, e parâmetros metabólicos e antropométricos em idosas de Salvador, Bahia

Abstract

Introduction: The reduction in bone mineral density (BMD) due to osteoporosis induces bone fragility and susceptibility to fractures, especially in postmenopausal and elderly women. The RANK/RANKL/OPG system is a key molecular mechanism in the determination of BMD. It is under influence of several factors, such as dyslipidemia, hyperglycemia, hypertension and changes in the immune and hormonal system, which contribute to the development of osteoporosis. However, clinical studies are still contradictory, with findings showing a positive, negative or no correlation between these factors and bone loss. This divergence can be partially attributed to genetic variations between subjects and, also, to other factors such as ethnicity and life habits. Objectives: It aims to investigate correlations among BMD, polymorphisms of the osteoprotegerin (OPG) and RANK ligand (RANKL) genes, and metabolic and anthropometric parameters in elderly women enrolled in an educational institute for elderly in Salvador-BA. Methods: This is a cross-sectional study, which included 67 elderly women aged ≥60 years. For data collection, an interview followed by physical examination was performed to obtain sociodemographic, clinical and anthropometric information. Blood samples were collected for assessing serum levels of hormones, fasting glucose and Hb1AC, total cholesterol and fractions, C-reactive protein (CRP), and other molecules. The determination of BMD (in g/cm2) was acquired by bone densitometry of femoral neck and lumbar spine by using DEXA technology. The investigated SNPs were rs2062377, rs3102735, rs6469804 from TNFRSF11B gene that encodes OPG; and rs9594738, rs9525641 from TNFSF11 that encodes RANKL, and they were genotyped from genomic DNA. Statistical analysis was performed using the Statistical Package for Social Sciences for Windows, version 21.0. Statistical significance level considered was p≤0.05. Results: Two papers were generated from this research. In paper 1, every anthropometric variable showed a significant correlation with BMD in both femoral neck and lumbar spine sites. In addition, total cholesterol, LDL and estradiol were correlated with lumbar spine BMD, while CRP was correlated with femoral neck BMD. In the multivariate linear regression analysis, body weight, estradiol and LDL were able to predict the variability of BMD in the investigated bone sites. In paper 2, we did not observe a significant association among the genotypic and allelic frequencies of any proposed SNP between individuals with normal BMD and low BMD of the investigated bone sites, despite the TT-rs9594738 and TT-rs9525641 have presented the highest values of mineral mass bone in the lumbar spine and femoral neck, respectively. In bivariate logistic regression, we observed that the use of antihypertensive drugs significantly reduced the chances of low BMD in both femoral neck and lumbar spine in elderly women. Conclusion: Among all investigated variables, body weight and estradiol exert the greatest influence on the determination of femoral neck BMD, while body weight and LDL exert the greatest influence on lumbar spine BMD in elderly women. In addition, the use of antihypertensive drugs seems to be the main factor that reduces the odds of low BMD in femoral neck and lumbar spine in physical active elderly women of mixed ancestry.