The Role of Candidate Gene Polymorphisms in Postmenopausal- and Thyroid Hormone-Stimulated Bone Loss

Osteoporosis (OP) is one of the most common chronic disorders; the disabilities that result from osteoporotic fractures (OPF) worldwide have an enormous impact on the health of individuals, societies and economies. Genetic factors together with environmental factors play an important role in regulating the development of osteoporosis as well as contributing to the susceptibility of osteoporotic fractures. Our aims were to analyze some genetic factors that affected osteoporosis permitting early detection of individuals who are at risk for the disease, and allowing for early initiation of preventive therapy. We have studied the role of certain gene polymorphisms of proteins having biological effects on bone metabolism in postmenopausal and thyroid hormone stimulated bone loss. We have also looked at the possible functional contributions of these genes to the pathogenesis of hyperthyroidism in toxic adenoma (TA), as one of the major group responsible for secondary osteoporosis. Our results demonstrate that COL1A1 gene G1245T (Sp1) and CaSR gene A986S polymorphisms might cause a predisoisition to postmenopausal osteoporosis and might also be a prognostic marker of the disease. We could not prove the direct clinical significance of these gene variants on bone fracture. Based on our observation we conclude that IL-1RN VNTR polymorphism may not play an essential role in the determination of BMD in postmenopausal osteoporosis; however, our results support a hypothesis that it may influence the bone fracture risk, independent of BMD. This is the first study reporting the possible functional contribution of ER alpha gene XbaI and IGF -I gene CA repeat polymorphism in the pathogenesis of toxic adenoma. Based on our data VDR gene BsmIand IL-1RN gene VNTR polymorphisms do not appear to have an impact on the development of TA. Our results also raise the possibility of the contribution of this microsatellite repeat variant of IGF-I gene in bone loss as the consequence of TA. We have not confirmed the role of ER alpha XbaI-, VDR BsmI and IL1RN gene VNTR polymorphisms in predicting low BMD caused by toxic adenoma.