Association between candidate genes and FRAX scores in postmenopausal women

Purpose Single nucleotide polymorphisms (SNPs) have been associated with BMD and bone fracture risk. The aim of this study was to assess the possible association between FRAX scores and specific SNPs in Italian osteopenic and osteoporotic postmenopausal women. Methods We enrolled 54 postmenopausal women with osteoporosis or osteopenia. FRAX (a computer-based free algorithm that provides the 10-year probability of fractures on the basis of classic risk factors) and BMD were obtained in every patient. We included 13 SNPs in the ESR1, OPG, RANK-L, VDR, PTH, CASR, COL1A1, CALCR, ACTN3 and TPRV6 candidate genes. We tested the association of principal component analysis scores based on individual multi-locus genotypes with FRAX. Results A FRAX_M > = 20% was found in 20.3% and a FRAX_H > = 3% in 51.8% of patients. Twenty-four patients had a fragility fracture. At the level of single-locus associations, a significant difference (p = 0.046) was obtained for FRAX_H and the haplotype ESR1(GC), with mean values of 3.9 vs. 7.7 among non-carriers vs. carriers. In particular, patients character¬ized by high FRAX_M and FRAX_H values shared haplotype (GT) at PTH and allele G at OPG. On the opposite, patients in the low-risk FRAX score were characterized by COL1A1 allele A, CASR allele T, VDR haplotypes (GA) and (AA). Conclusion In postmenopausal Italian women an appropriate combination of haplotypes/alleles at PTH and OPG genes is associated with high mean FRAX values. Long term studies would allow to assess if combining multi-locus genetic analyses with FRAX scores could empower physicians to tailor personalized preventive early strategies for osteoporosis.