BACKGROUND The purpose of the study was to investigate the correlation between rs4754 and rs6840362 polymorphisms of secreted phosphoprotein 1 (SPP1) gene and fracture risk. MATERIAL AND METHODS rs4754 and rs6840362 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 130 patients with fracture and 107 healthy controls matched with the former by age and sex. Hardy-Weinberg equilibrium (HWE) was assessed in the control group based on the genotype distributions of SSP1 poylmorphisms. The differences in genotype, allele, and haplotype frequencies between cases and controls were detected by the chi-square test, and the relative risk of fracture is expressed by odds ratio (OR) and 95% confidence interval (CI). The linkage disequilibrium (LD) and haplotype analyses were conducted with HaploView software. RESULTS The TT genotype in rs4754 had significant difference in patients with fracture and controls (10.77% and 4.59%, P=0.04) and the results showed that people carrying TT genotype of rs4754 were more susceptible to fractures than CC genotype carriers (OR=3.00, 95%CI=1.02-8.89). The T allele also had 1.54 times higher risk of fractures (OR=1.54, 95%CI=1.04-2.30), but this was not true for the rs6840362 polymorphism. LD between the 2 polymorphisms and haplotype C-T (rs6840362-rs4754) increased the susceptibility to fracture (OR=2.01, 95%CI=1.23-3.28). CONCLUSIONS SPP1 rs4754 polymorphism may be related to risk of fracture, but not rs6840362.