title: Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women.
abstract: OBJECTIVE
  An oestrogen-receptor-alpha (ERalpha) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERalpha gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post-menopausal women in relation to ERalpha gene polymorphism.
  
  
  METHODS
  Subjects consisted of 124 Thai post-menopausal women. 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 osteoporosis as defined by BMD T-score less than - 2.5. Subjects were randomly allocated 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. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean +/- SEM. Capital P represents the absence of the restriction site while lower-case p indicates the presence of the restriction site.
  
  
  RESULTS
  For subjects on 0.625 mg CEE, BMD at L2-4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2-4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 +/- 1.5%, P < 0.001) and PP genotypes (n = 13, + 6. 9 +/- 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 +/- 2.1%, P = NS). After adjusting for age and years since 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 ERalpha gene polymorphism affects skeletal response to oestrogen in post-menopausal women. The effect of ERalpha gene polymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover. Determination of ERalpha genotype may help identify post-menopausal women who will have more skeletal benefit from oestrogen therapy.
authors.affiliation: Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: B
authors.initials: B
authors.lastname: Ongphiphadhanakul
authors.forename: S
authors.initials: S
authors.lastname: Chanprasertyothin
authors.forename: P
authors.initials: P
authors.lastname: Payatikul
authors.forename: S S
authors.initials: SS
authors.lastname: Tung
authors.forename: N
authors.initials: N
authors.lastname: Piaseu
authors.forename: L
authors.initials: L
authors.lastname: Chailurkit
authors.forename: S
authors.initials: S
authors.lastname: Chansirikarn
authors.forename: G
authors.initials: G
authors.lastname: Puavilai
authors.forename: R
authors.initials: R
authors.lastname: Rajatanavin
mesh_terms: D015519:Bone Density / Q000187:drug effects*; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D004966:Estrogens, Conjugated (USP); D011960:Receptors, Estrogen