Uitterlinden AG et al. (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med 145: 255–264

After a multitude of studies, it has become clear that assessments of bone mineral density and known risk factors for osteoporosis are insufficient to identify individuals who are likely to sustain osteoporotic fractures. It has been postulated, therefore, that some of the unknown risk factors are genetic. Several polymorphisms in the vitamin D receptor gene, VDR, have been investigated for associations with fracture, but study results are inconsistent. Uitterlinden et al. have conducted a large-scale meta-analysis of studies from across the world, to investigate the effect on fracture incidence of four restriction-fragment-length polymorphisms in VDR: FokI; BsmI; ApaI; TaqI; and one CDX2-promoter polymorphism.

Data were gathered for 26,242 participants (18,405 women), of whom 6,067 had a history of fractures and 2,088 had vertebral fractures. Genotyping and analysis of data revealed that the CDX2 polymorphism was associated with a reduced risk of fracture; however, the decrease in risk was modest (risk reduction 9%, 95% CI 0–18%, P = 0.039) and restricted to vertebral fractures. No other associations were found.

These results contradict previous findings of an association between these polymorphisms and bone mineral density, and do not support the existence of a relationship between VDR polymorphisms and the incidence of osteoporotic fracture. The authors caution that their finding of an association between the CDX2 polymorphism and vertebral fracture might simply be a chance finding, because of the large number of analyses they performed.