Abstract
Background: Several studies have examined the association between vitamin D receptor (VDR) polymorphisms and osteoporotic fracture risk; however, the results are not uniform. Furthermore, many new articles have been published, and therefore, an updated meta-analysis was performed to further explore these issues. Objectives: The aim of the study was to investigate the association between VDR, BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and osteoporotic fracture risk. Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between VDR BsmI, ApaI, TaqI, FokI, and Cdx2 polymorphisms and the risk of osteoporotic fracture. We also used the false-positive reporting probability (FPRP) test and the Venice criteria to evaluate the credibility of the statistically significant associations. Results: Overall, this study found that the VDR ApaI and BsmI polymorphisms significantly increased the risk of osteoporotic fracture in European countries and America, respectively. However, when sensitivity analysis was performed after excluding low-quality and Hardy–Weinberg disequilibrium (HWD) studies, it was found that only individuals with the double-mutated genotype have an increased risk of osteoporotic fracture in European countries. In addition, when the credibility of the positive results was assessed, it was found that the positive results were not credible. Conclusion: This meta-analysis indicates that there may be no significant association among the polymorphisms of VDR BsmI, ApaI, TaqI, FokI, and Cdx2 and the risk of osteoporotic fracture. The increased risk of osteoporotic fracture is most likely due to false-positive results.
Highlights
Osteoporosis is characterized by reduced bone density and increased bone fragility, leading to an increased risk of fracture (Recker, 2005)
A total of 221 relevant studies were retrieved, and 23 articles met our criteria (5,844 osteoporotic fracture cases and 19,339 controls), of which 18 articles examined vitamin D receptor (VDR) BsmI, eight studies discussed VDR ApaI, nine studies reported VDR TaqI, seven studies documented VDR FokI, and three studies investigated VDR Cdx2, and how each of these polymorphisms correlates with osteoporotic fracture risk
18, 5, and 1 case–control studies have been conducted in European, American, and Asian populations, respectively. Four studies discussed these associations in men, and 22 studies analyzed these relationships in women
Summary
Osteoporosis is characterized by reduced bone density and increased bone fragility, leading to an increased risk of fracture (Recker, 2005). It is important to explore the underlying pathogenic factors. Many studies have found that genetic factors play an important role in the pathogenesis of osteoporosis (Jin and Ralston, 2001; Recker and Deng, 2002). Dozens of risk genes for osteoporosis have been identified, of which ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11 are thought to be involved in bone mineral density (BMD) homeostasis, bone remodeling, and bone matrix composition, and influence BMD and osteoporotic fractures. Several studies have examined the association between vitamin D receptor (VDR) polymorphisms and osteoporotic fracture risk; the results are not uniform. Many new articles have been published, and an updated metaanalysis was performed to further explore these issues
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