GENETIC POLYMORPHISMS ASSOCIATED WITH OSTEOPOROSIS SUSCEPTIBILITY: A SYSTEMATIC REVIEW OF MOLECULAR VARIANTS AND BONE MINERAL DENSITY OUTCOMES

Abstract

Background: Osteoporosis is a multifactorial skeletal disease, which is marked by decreased bone mineral density (BMD) and increased susceptibility to fractures, and genetic factors contribute to a significant share of inter individual variation in bone mass. Despite the fact that many molecular variants have been associated with the susceptibility of osteoporosis, the uniformity and clinical implication of these associations are yet to be fully established. The purpose of this systematic review was to review the available evidence on genetic polymorphisms and BMD outcomes and osteoporosis risk.

Methodology: A systematic literature review was performed in PubMed, Scopus, Embase, Web of Science, and Cochrane Library to find original genetic association studies comparing molecular variants to BMD or osteoporosis. Studies that used human population as the subject of observation and reported genotypic data that used quantitative BMD or fracture outcomes were included. Conference abstracts, reviews, meta-analyses and animal studies were excluded. Information was obtained on the characteristics of the study, genes of interest, skeletal locations that were evaluated, and reported associations. The quality of methodology was assessed with the help of standardized criteria, and the results were synthesized on a qualitative level.

Results: Nine of the eligible studies with over 11,000 participants who were of Asian and European origin were included. Regular correlations were found between the polymorphisms in the important bone regulatory genes and lower BMD. TNFRSF11B (osteoprotegerin) variants were repeatedly associated with reduced lumbar spine BMD and high fracture risk, whereas LRP5 variants were strongly associated with decreased spine and femoral neck BMD. Other VDR, FGFR1, FABP3, and TIMP2 variants were linked to site-specific loss of BMD and risk of a fracture. The majority of genetic influences were small but directional in populations.

Conclusion: Genetic polymorphisms in a variety of bone remodeling pathways play an important role in the variation of BMD and osteoporosis susceptibility. These results endorse a polygenic theory of skeletal fragility and emphasize the possibility of the use of genetic profiling in individual risk assessment and prevention measures.