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 language | English |
|---|---|
| Pages (from-to) | 371-379 |
| Number of pages | 9 |
| Journal | Maturitas |
| Volume | 53 |
| Issue number | 4 |
| DOIs | |
| State | Published - Mar 20 2006 |
| Externally published | Yes |
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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 journal › Article
}
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.
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U2 - 10.1016/j.maturitas.2005.07.007
DO - 10.1016/j.maturitas.2005.07.007
M3 - Article
C2 - 16139450
AN - SCOPUS:33644624542
VL - 53
SP - 371
EP - 379
JO - Maturitas
JF - Maturitas
SN - 0378-5122
IS - 4
ER -