Bone Fracture Incidence in Postmenopausal Women: Results of a 10 Year Follow Up in a RAC-OST-POL Study of rs1544410, rs7975232 and rs731236 Polymorphisms.

Background: The clinical significance of the genetic influence of vitamin D receptor polymorphisms has still not been well-analyzed.

Objectives: To verify whether rs1544410, rs7975232 and rs731236 polymorphisms are associated with a higher 10-year fracture risk in postmenopausal women.

Methods: The study group was a subset of a pre-defined population as part of the broader epidemiological research called the RAC-OST-POL Study and consisted of 358 postmenopausal women, chosen randomly from Racibórz (Poland) inhabitants (mean baseline age 65 ± 6.9 years, BMI 31.2 ± 5.5 kg/m). From all participants' medical history, data concerning co-morbidities, fracture history, the medication used, parental history of bone fractures, cigarettes and alcohol use were taken at baseline. Moreover, rs1544410, rs7975232 and rs731236 polymorphisms were analyzed. Next, over the following 10 years, participants were contacted once a year and questioned concerning new fractures events and their circumstances.

Results: We did not find statistically significant main effects on the fracture incidence of single-polymorphism variants. However, there were some significant findings dependent on the co-existence of these polymorphisms and medical factors. Women with a positive history of parental fracture and configuration of CC rs7975232, AA rs731236 and CC rs1544410 had a higher fracture incidence. The risk of bone fracture was also significantly higher in the group of heterozygotes of AC rs7975232 if their BMI value was in the categories of normal weight or overweight, or if they were treated with calcium or vitamin D.

Conclusions: Polymorphisms of rs1544410, rs7975232 and rs731236 are connected with the fracture incidence in postmenopausal women. Nevertheless, its influence should be considered with co-existing clinical factors, especially paternal fracture history, prior fracture, BMI value, any osteoporotic treatment or calcium/vit. D supplementation.