The RANKL/RANK/OPG signal trail: significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis

Abstract

Objectives: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL –643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women.

Material and methods: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2–L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method.

Results: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL –643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL –643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed.

Conclusions: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The –643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.