Genetic influence on osteoporosis and fracture risk: Outcome of genome-wide association studies – A systematic review

Abstract

This systematic review aimed to identify genome-wide association studies (GWASs) highlighting the genes and single-nucleotide polymorphisms linked to osteoporosis and fragility fracture risk. We searched the search engines EMBASE, MEDLINE, Scopus, Web of Science, Science Citation Index, and Cochrane database of systematic reviews between 2005 and May 2022. The articles were reviewed individually for risk of bias and found no variances in the papers designated for analysis. We analyzed 63 studies with 1,326,798 patients, which included postmenopausal and premenopausal women. Thirty-one studies used dual-energy x-ray absorptiometry (DXA) for the diagnosis. Three studies used ultrasonography, and one used peripheral quantitative computed tomography (pQCT) to diagnose osteoporosis. For the risk of fragility fractures, 15 studies with 744,123 were analyzed, which used DXA in 12, two studies of ultrasonography, and one of radiography. Three studies were reported in premenopausal women and three in children with 18,203 subjects. Our analysis showed that 150 genes, 515 loci that target bone mineral density and 15 loci that increase fracture risk in osteoporosis have been identified. Osteoporosis and fragility fractures are common in the Saudi Arabian population. The GWAS gives an understanding of the genetic basis of low bone density, osteoporosis, and fragility fractures. The GWAS data can provide new pathways to understanding the etiology of osteoporosis and a route to prevention and optimum treatment. Hence, we believe that we should conduct GWASs on osteoporosis sooner rather than later so that we can advise at-risk individuals to change their lifestyle so that they can limit complications of osteoporosis and related complications.