Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen

P. B. Rapuri, John Christopher G. Gallagher, J. A. Knezetic, V. Haynatzka

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objectives: Association studies between estrogen receptor α (ERα) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERα 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 ERα 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 ERα 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 ERα 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 ERα, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalMaturitas
Volume53
Issue number4
DOIs
StatePublished - Mar 20 2006
Externally publishedYes

Fingerprint

Estrogen Receptor alpha
Bone Remodeling
Polymorphism
Bone
Estrogens
Genes
Genotype
Estrogen Receptors
Bone Density
Minerals
Hormones
Bone and Bones
Therapeutics
Osteocalcin
Urine
Longitudinal Studies
Biomarkers
Placebos
Femur Neck
Serum

All Science Journal Classification (ASJC) codes

  • Aging
  • Obstetrics and Gynecology

Cite this

Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. / Rapuri, P. B.; Gallagher, John Christopher G.; Knezetic, J. A.; Haynatzka, V.

In: Maturitas, Vol. 53, No. 4, 20.03.2006, p. 371-379.

Research output: Contribution to journalArticle

@article{d41ff9c10ecb41b6b4c93e5c8a1b55fb,
title = "Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen",
abstract = "Objectives: Association studies between estrogen receptor α (ERα) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERα 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 ERα 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 ERα 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 ERα 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 ERα, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.",
author = "Rapuri, {P. B.} and Gallagher, {John Christopher G.} and Knezetic, {J. A.} and V. Haynatzka",
year = "2006",
month = "3",
day = "20",
doi = "10.1016/j.maturitas.2005.07.007",
language = "English",
volume = "53",
pages = "371--379",
journal = "Maturitas",
issn = "0378-5122",
publisher = "Elsevier Ireland Ltd",
number = "4",

}

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, John Christopher G.

AU - Knezetic, J. A.

AU - Haynatzka, V.

PY - 2006/3/20

Y1 - 2006/3/20

N2 - Objectives: Association studies between estrogen receptor α (ERα) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERα 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 ERα 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 ERα 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 ERα 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 ERα, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.

AB - Objectives: Association studies between estrogen receptor α (ERα) gene polymorphisms and bone mineral density (BMD) have yielded inconsistent results. In the present study we evaluated the influence of XbaI and PvuII ERα 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 ERα 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 ERα 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 ERα 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 ERα, PP and XX genotypes have lower bone remodeling, lower rates of bone loss and benefit more from hormone therapy.

UR - http://www.scopus.com/inward/record.url?scp=33644624542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644624542&partnerID=8YFLogxK

U2 - 10.1016/j.maturitas.2005.07.007

DO - 10.1016/j.maturitas.2005.07.007

M3 - Article

VL - 53

SP - 371

EP - 379

JO - Maturitas

JF - Maturitas

SN - 0378-5122

IS - 4

ER -