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Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen.
Maturitas. 2006 Mar 20; 53(4):371-9.M

Abstract

OBJECTIVES

Association studies between estrogen receptor alpha (ERalpha) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERalpha gene polymorphisms on BMD, biochemical markers, rates of bone loss and the response to estrogen/hormone therapy (ET/HT) in elderly postmenopausal women.

METHODS

At baseline, we measured the association between ERalpha genotypes and BMD and biochemical markers in 489 elderly women, mean age 71 +/- 3 years. In the longitudinal study, the changes in the same measures were determined in 96 women on placebo and in 79 women receiving the ET/HT for 3 years. The XbaI and PvuII ERalpha polymorphisms were determined by polymerase chain reaction (PCR). BMD measurements for spine, femoral neck and total body were performed by DEXA, and biochemical indices were measured by standard methods.

RESULTS

Neither the PvuII nor the XbaI ERalpha gene polymorphisms were associated with baseline BMD and biochemical indices. In the longitudinal study, there were trends for higher bone loss in the placebo group in the genotypes pp or xx compared to PP or XX genotypes, but the changes were not significant. However, the changes in the bone markers were significantly (p < 0.05) higher in genotype group pp compared to PP (serum osteocalcin, 4.9 +/- 7.0% versus -13.4 +/- 6.7%; urine NTx:Cr ratio, 32.3+/-10.3% versus -2.5 +/- 10.3%) or xx compared to XX (serum osteocalcin, 7.5 +/- 6.4% versus -15.6+/-7.3%; urine NTx:Cr ratio, 39.4 +/- 9.2% versus -8.84+/-10.7%). At the end of 3 years, the mean urine NTx:Cr ratio was 78.7 +/- 9.0 versus 44.6 +/- 4.9 in pp versus PP (p < 0.05) and 75.5 +/- 10.7 versus 48.7 +/- 5.4 in xx versus XX (p < 0.05) genotypes. The response in total body BMD to ET/HT treatment was significantly higher in women with the PP genotype compared to pp genotype (2.48 +/- 0.55% versus 0.66 +/- 0.46%). Similar trends were seen at other skeletal sites for both XX and PP compared to pp and xx genotypes.

CONCLUSION

Women with ERalpha, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.

Authors+Show Affiliations

Bone Metabolism Unit, Creighton University, School of Medicine, 601 North 30th Street, Room 6718, Omaha, NE 68131, USA. thiyyari@creighton.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16139450

Citation

Rapuri, P B., et al. "Estrogen Receptor Alpha Gene Polymorphisms Are Associated With Changes in Bone Remodeling Markers and Treatment Response to Estrogen." Maturitas, vol. 53, no. 4, 2006, pp. 371-9.
Rapuri PB, Gallagher JC, Knezetic JA, et al. Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. Maturitas. 2006;53(4):371-9.
Rapuri, P. B., Gallagher, J. C., Knezetic, J. A., & Haynatzka, V. (2006). Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. Maturitas, 53(4), 371-9.
Rapuri PB, et al. Estrogen Receptor Alpha Gene Polymorphisms Are Associated With Changes in Bone Remodeling Markers and Treatment Response to Estrogen. Maturitas. 2006 Mar 20;53(4):371-9. PubMed PMID: 16139450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. AU - Rapuri,P B, AU - Gallagher,J C, AU - Knezetic,J A, AU - Haynatzka,V, Y1 - 2005/08/31/ PY - 2005/03/21/received PY - 2005/07/06/revised PY - 2005/07/20/accepted PY - 2005/9/6/pubmed PY - 2006/7/29/medline PY - 2005/9/6/entrez SP - 371 EP - 9 JF - Maturitas JO - Maturitas VL - 53 IS - 4 N2 - OBJECTIVES: Association studies between estrogen receptor alpha (ERalpha) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERalpha gene polymorphisms on BMD, biochemical markers, rates of bone loss and the response to estrogen/hormone therapy (ET/HT) in elderly postmenopausal women. METHODS: At baseline, we measured the association between ERalpha genotypes and BMD and biochemical markers in 489 elderly women, mean age 71 +/- 3 years. In the longitudinal study, the changes in the same measures were determined in 96 women on placebo and in 79 women receiving the ET/HT for 3 years. The XbaI and PvuII ERalpha polymorphisms were determined by polymerase chain reaction (PCR). BMD measurements for spine, femoral neck and total body were performed by DEXA, and biochemical indices were measured by standard methods. RESULTS: Neither the PvuII nor the XbaI ERalpha gene polymorphisms were associated with baseline BMD and biochemical indices. In the longitudinal study, there were trends for higher bone loss in the placebo group in the genotypes pp or xx compared to PP or XX genotypes, but the changes were not significant. However, the changes in the bone markers were significantly (p < 0.05) higher in genotype group pp compared to PP (serum osteocalcin, 4.9 +/- 7.0% versus -13.4 +/- 6.7%; urine NTx:Cr ratio, 32.3+/-10.3% versus -2.5 +/- 10.3%) or xx compared to XX (serum osteocalcin, 7.5 +/- 6.4% versus -15.6+/-7.3%; urine NTx:Cr ratio, 39.4 +/- 9.2% versus -8.84+/-10.7%). At the end of 3 years, the mean urine NTx:Cr ratio was 78.7 +/- 9.0 versus 44.6 +/- 4.9 in pp versus PP (p < 0.05) and 75.5 +/- 10.7 versus 48.7 +/- 5.4 in xx versus XX (p < 0.05) genotypes. The response in total body BMD to ET/HT treatment was significantly higher in women with the PP genotype compared to pp genotype (2.48 +/- 0.55% versus 0.66 +/- 0.46%). Similar trends were seen at other skeletal sites for both XX and PP compared to pp and xx genotypes. CONCLUSION: Women with ERalpha, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy. SN - 0378-5122 UR - https://www.unboundmedicine.com/medline/citation/16139450/Estrogen_receptor_alpha_gene_polymorphisms_are_associated_with_changes_in_bone_remodeling_markers_and_treatment_response_to_estrogen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5122(05)00194-5 DB - PRIME DP - Unbound Medicine ER -