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

OBJECTIVE An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausa...

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Published in:	Clinical endocrinology (Oxford) Vol. 52; no. 5; pp. 581 - 585
Main Authors:	Ongphiphadhanakul, B., Chanprasertyothin, S., Payatikul, P., Tung, S. Sae, Piaseu, N., Chailurkit, L., Chansirikarn, S., Puavilai, G., Rajatanavin, R.
Format:	Journal Article
Language:	English
Published:	Oxford BSL Blackwell Science Ltd 01-05-2000 Blackwell Wiley Subscription Services, Inc
Subjects:	Biological and medical sciences Bone Density - drug effects Drug Administration Schedule Estrogen Replacement Therapy Estrogens, Conjugated (USP) - administration & dosage Female Genital system. Reproduction Humans Medical sciences Middle Aged Osteoporosis, Postmenopausal - drug therapy Osteoporosis, Postmenopausal - genetics Pharmacology. Drug treatments Polymorphism, Genetic Receptors, Estrogen - genetics Treatment Outcome Tropical medicine Thailand Asia Human Replacement therapy Treatment efficiency Estrogen Density Genetic determinism Bone mass Postmenopause Adult Female Bone mineral density Polymorphism Hormonal receptor
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Summary:	OBJECTIVE An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα 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 ERα gene polymorphism. PATIENTS AND MEASUREMENTS 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 ERα gene polymorphism affects skeletal response to oestrogen in post‐menopausal women. The effect of ERα gene polymorphism appears to be site‐specific and does not relate to biochemical markers of bone turnover. Determination of ERα genotype may help identify post‐menopausal women who will have more skeletal benefit from oestrogen therapy.
Bibliography:	istex:8CA71A12C60A0C3589991358A5405EA8E047E7DE ark:/67375/WNG-BQRQBV50-2 ArticleID:CEN979 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23
ISSN:	0300-0664 1365-2265
DOI:	10.1046/j.1365-2265.2000.00979.x