Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women

High bone resorption by the osteoclast results in osteoporosis, a disease a ffecting 40% of women after the menopause. Calcitonin, used to treat osteop orosis, inhibits bone resorption via receptors located on the osteoclasts, Two alleles of the calcitonin receptor gene (CTR) exist: a base mutation T- ->C in the third intracellular C-terminal domain changes a proline (CCG) at position 447 to a leucine (CTG). We therefore studied the distribution of these alleles in a cohort of 215 post-menopausal Caucasian women suffering or not from osteoporotic fractures. The region of interest within the point mutation was amplified by PCR and screened for single strand conformation polymorphism. This work was followed by DNA sequencing of the fragments amp lified. We found that bone mineral density (BMD) at the femoral neck was si gnificantly higher in heterozygous subjects with the Rr genotype compared w ith the homozygous leucine (RR) and homozygous proline (rr) genotypes, Also , a decreased fracture risk was observed in heterozygote subjects. In concl usion, our results suggest that polymorphism of CTR could be associated wit h osteoporotic fractures and BMD in a population of post-menopausal women. CTR heterozygotes could produce both alleles of the receptor,The heterozygo us advantage effect of Rr subjects could explain their protection against o steoporosis: higher bone density and decreased fracture risk. Establishing the genotype of the CTR gene in post-menopausal women could be of value in evaluating their risk of developing fractures.