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Objective To discuss the relationship between gene polymorphism of FDPS and LRP5 and the osteoporosis in postmenopausal women. Methods From June 2017 to August 2019? 364 postmenopausal women were divided into the osteoporosis group (228 patients) and the normal group (136 patients). Clinical data and blood samples were collected from all the participants, the genetic polymorphism of FDPS rs2297480 and LRP5 rs3736228 were evaluated with the method of TaqMan fluorescent probe and restriction fragment length polymorphism (PCR-RELP). Analysis of relationship of genetic polymorphism with bone mineral density (BMD) and osteoporosis. Results The BMD values of lumbar spine and total hip joint in FDPS RS2297480 TT genotype patients were significantly lower, and the presence of T alleles was significantly correlated with osteoporosis. The BMD values of femoral neck and total hip joint in LRP5 rs3736228 patients with CC genotype were lower. Conclusion In postmenopausal women with osteoporosis, there is a strong correlation between BMD values and FDPS gene polymorphisms and a low correlation with LRP5 gene polymorphisms. [ABSTRACT FROM AUTHOR]