Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women

OBJECTIVE An oestrogen-receptor-alpha (ER alpha) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ER alpha gene polymorphism is associated with a functional difference, we a ssessed the response in bone mineral density (BMD) to oestrogen therapy in postmenopausal women in relation to ER alpha gene polymorphism. PATIENTS AND MEASUREMENTS Subjects consisted of 124 Thai post-menopausal wo men, Sixty-three of the women were less than 6 years post-menopausal and 61 were more than 10 years post-menopausal with vertebral or femoral osteopor osis as defined by BMD T-score less than - 2.5. Subjects were randomly allo cated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE), All subjects also took 5 mg medroxyprogesterone acetate, V ertebral and femoral neck BMD were measured at baseline and 1 year after tr eatment. Data were expressed as mean +/- SEM, Capital P represents the abse nce of the restriction site while lower-case p indicates the presence of th e restriction site. RESULTS For subjects on 0.625 mg GEE, BMD at L2-4 increased significantly a fter 1 year in those with pp (n=20) Pp (n=29) and PP genotypes (n=8) (P<0.0 01). However, in subjects on 0.3 mg GEE, BMD at L2-4 increased significantl y after 1 year in subjects with Pp (n = 34, + 7.6 +/- 1.5%, P< 0.001) and P P genotypes (n = 13, + 6.9 +/- 1.0%, P< 0.001), but not in those with pp ge notype (n=20, +2.3 +/- 2.1%, P = NS). After adjusting for age and years sin ce menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P<0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype. CONCLUSIONS We conclude that ER alpha gene polymorphism affects skeletal re sponse to oestrogen in post-menopausal women. The effect of ER alpha gene p olymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover, Determination of ER alpha genotype may help ident ify post-menopausal women who will have more skeletal benefit from oestroge n therapy.