Relationship Between RANK and RANKL Gene Polymorphisms with Osteoporosis in Rheumatoid Arthritis Patients

Background: Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. In the present study, we aimed to evaluate the relationship between polymorphisms of the receptor activator of the nuclear factor kappa B (RANK) gene; the receptor activator of the nuclear factor kappa B ligand (RANKL) gene; and RANKL levels with osteoporosis in postmenopausal RA patients.

Design And Methods: One hundred seventy-two postmenopausal female patients and 176 age- and sex-matched controls were enrolled in the study. All subjects were genotyped for the presence of RANK C575T (rs1805034) and RANKL C290T (rs9525641) gene polymorphisms. RANKL levels, bone mineral density (BMD), and biochemical markers were also obtained.

Results: Women with the RANK CC genotype were significantly (2X) more likely to develop osteoporosis than those with the TT genotype (p = 0.024). A significant association was also observed between the RANKL 290TT genotype and both BMD and RANKL levels. In addition, individuals with the -290TT genotype were twice as likely to develop osteoporosis as those with the CC genotype (p < 0.001).

Conclusions: Postmenopausal women with RA, carrying either the RANKL-290T allele or possessing the RANK 575CC genotype were more likely to develop osteoporosis. Moreover, our results suggested that the polymorphism 290C>T could be considered a risk factor for genetic susceptibility to osteoporosis and low BMD.