Skip to main content
Erschienen in: BMC Endocrine Disorders 1/2018

Open Access 01.12.2018 | Research article

Associations between ERα/β gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis

verfasst von: Heping Zhu, Jiannong Jiang, Qiang Wang, Jun Zong, Liang Zhang, Tieliang Ma, Youjia Xu, Leiyan Zhang

Erschienen in: BMC Endocrine Disorders | Ausgabe 1/2018

Abstract

Background

Many studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERβ gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.

Methods

PubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association.

Results

Overall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERβ RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations.

Conclusion

Each ERα and ERβ gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.
Abkürzungen
BMD
Bone mineral density
CI
Confidence interval
ER
Estrogen receptor
Lactase
LCT
OR
Odds ratios
PMOP
Postmenopausal Osteoporosis
PTH
Parathyroid Hormone
TGF-β
Transforming growth factor-β
WMD
Weight mean difference

Background

Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder characterized by low bone mineral density (BMD) and increased fracture risks [13]. It is estimated that osteoporosis affects approximately 10 million American adults, with another 34 million being at high risk due to low bone mass [4].
The pathophysiology of PMOP is considered as a disorder or negative imbalance of bone metabolism and remodeling, with bone resorption outpacing bone formation [3], suggesting that vitamin D and parathyroid hormone (PTH) and other factors related to bone resorption and formation may play a key role in the underlying mechanism and pathophysiology of PMOP [58]. Furthermore, genetic factors including genes and gene polymorphisms may also play an important role in the development of PMOP [9].
Estrogen is another important hormone that plays an important role in the pathogenesis of PMOP, knowing that reduced ovarian production of estrogen after menopause is a cause for the initial phase of rapid bone loss and osteoporosis in women [3]. Estrogen is known as an important regulator of bone metabolism, and estrogen deficiency is believed to be the cause of BMD loss, increased mechanical loading-induced bone remodeling, and the development of PMOP [10]. Knowing that the action of estrogen is predominantly mediated by estrogen receptor (ER), including ERα and ERβ by binding to different ligands to mediate various biological effects [3, 10], more attention has been paid to the relationship between ERs and PMOP risk and BMD in postmenopausal women [1138]. However, the results of studies currently available about this issue are controversial.
Previous meta-analyses have been performed to assess the pooled effects of ER gene polymorphisms on BMD and fracture risk [3941]. WANG et al. [39] showed that the ERα XbaI (rs9340799) polymorphism was associated with BMD at diverse skeletal sites, and ERα PvuII (rs2234693) PP genotype played a role in protecting the lumbar spine but on the other hand might be a risk factor for the femoral neck fracture. However, to the best of our knowledge, no meta-analysis has been performed to explore the relationships between ER gene [ERα XbaI (rs9340799), ERα PvuII (rs2234693) and ERα G2014A (rs2228480)] and ERβ gene [ERβ AluI (rs4986938) and ERβ RsaI (rs1256049)] polymorphisms and PMOP susceptibility and BMD of the lumbar spine and femoral neck in postmenopausal women. To address these issues, we performed a meta-analysis of all currently available studies relating ER gene [ERα XbaI (rs9340799), ERα PvuII (rs2234693) and ERα G2014A (rs2228480)] and ERβ gene [ERβ AluI (rs4986938) and ERβ RsaI (rs1256049)] polymorphisms with PMOP risk and BMD.

Methods

Data sources and searches

We searched PubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library to identify case-control studies that investigated the associations between ERα gene polymorphisms [ERα XbaI (rs9340799), ERα PvuII (rs2234693) and ERα G2014A (rs2228480)] ERβ gene polymorphisms [ERβ AluI (rs4986938) and ERβ RsaI (rs1256049)] and osteoporosis susceptibility and BMD in postmenopausal women by using the following search terms (‘PMOP’ OR ‘Postmenopausal osteoporosis’ OR ‘Postmenopausal’) AND (‘Estrogen Receptor’ OR ‘ER’) AND (‘polymorphism’ OR ‘single nucleotide polymorphism’ OR ‘SNP’ OR ‘variation’). To analyze the pooled effects of ER gene polymorphisms on BMD, the following search terms were used: (‘PMOP’ OR ‘Postmenopausal osteoporosis’ OR ‘Postmenopausal’) AND (‘Estrogen Receptor’ OR ‘ER’) AND (‘polymorphism’ OR ‘single nucleotide polymorphism’ OR ‘SNP’ OR ‘variation’) AND (‘BMD’ OR ‘bone mineral density’). Then, one-by-one screening was performed by two authors according to the inclusion and exclusion criteria. No language restrictions were applied. Secondary searches of eligible studies were conducted by searching the reference lists of the selected studies, reviews or comments.

Inclusion and exclusion criteria

The inclusion criteria of our meta-analysis are as follows: (1) case-control studies; (2) studies on BMD and fracture risks in postmenopausal women with PMOP due to estrogen deficiency using postmenopausal women without PMOP or healthy volunteers as control; (3) studies reporting alleles and genotypes of at least one of the ER gene polymorphisms in women with or without PMOP: ERα XbaI (rs9340799), ERα PvuII (rs2234693), ERα G2014A (rs2228480), ERβ AluI (rs4986938) and ERβ RsaI (rs1256049); (3) studies reporting the sample size, mean and standard deviation (SD) of BMD (g/cm2) or BMD Z value in PMOP women with at least one of the ER genotypes; and (4) studies with sufficient data. The exclusion criteria were: (1) reviews or case reports without controls, and (2) studies with no availability of current data; and (3) duplicated reports.

Data extraction

Data from the eligible studies were extracted according to the inclusion and exclusion criteria by two authors, and a consensus was reached by discussion. In the study of associations between ER gene polymorphisms and PMOP risk, the following data were collected: author list, year of publication, ethnicity, sample size, alleles, genotype of each gene polymorphism and Hardy-Weinberg equilibrium (HWE). The following data were collected for analysis of differences in BMD in PMOP women with various ER genotypes: author list, year of publication, ethnicity, the number of cases and mean and SD of BMD (g/cm2) and BMD Z value.

Data synthesis and statistical analysis

We calculated odds ratios (OR) and 95% confidence interval (CI) to evaluate the association between ER gene polymorphisms and PMOP risk (osteoporosis occurred in postmenopausal women due to estrogen deficiency as represented by low BMD and increased fracture risks). The strength of association between ER gene polymorphisms and PMOP susceptibility was evaluated by OR and 95% CI under the allele contrast model, heterozygote model, homozygote model, dominant model and recessive model. HWE was calculated in the control population to evaluate the quality of the data by using chisquare test. Regarding the associations between BMD and ER gene polymorphisms, we compared BMD (g/cm2) and BMD Z value in PMOP women under the heterozygote and homozygote model respectively using the weight mean difference (WMD) and 95% CI. Heterogeneity of the included studies was examined by a chi-squared-based Q statistical test and quantified by I2 metric value. If I2 value was > 50% or P < 0.10, ORs and WMD were pooled by the random effect model; otherwise, the fixed effect model was used. Power analysis was performed using the Power and Precision V4 software (Biostat Inc., Englewood, USA). Sensitivity analysis was performed to assess the impact of each study on the combined effect of the present meta-analysis. Besides, subgroup analysis was also performed according to the ethnicity of the study populations. Stata 12.0 software (StataCorp, College Station, TX, USA) was used and a P < 0.05 was considered as statistically significant.

Results

Study selection and characteristics

A total of 28 studies [1138] were finally recruited in our meta-analysis. The study selection and inclusion process is shown in Fig. 1. Fourteen studies [1124] reported the association between ERα XbaI and PMOP risk, and the number of the included studies that reported the alleles and genotypes of ERα PvuII, ERα G2014A, ERβ AluI and ERβ RsaI was 16 [1125, 32], 4 [2629], 4 [17, 3032] and 2 [30, 31], respectively. Ivanova et al. [20], Albagha et al. [33], Aerssens et al. [24], Kurt et al. [34], Ge et al. [36] and Pérez et al. [19] reported both the lumbar spine and femoral neck BMD (g/cm2). Jeedigunta et al. [15] and Kurabayashi et al. [35] were also recruited in the assessment of the lumbar spine BMD (g/cm2) in ERα XbaI genotypes. Ivanova et al. [20], Albagha et al. [33] and An et al. [38] reported both the lumbar spine and femoral neck Z values. Shang et al. [11] also studied the lumbar spine Z value in PMOP with ERα XbaI genotypes. Ten studies [15, 19, 20, 23, 24, 3337] and 8 studies [19, 20, 23, 24, 33, 34, 36, 37] were recruited in the pooled analysis of differences in lumbar spine and femoral neck BMD (g/cm2) in PMOP women carrying ERα PvuII, respectively. With regard to differences in lumbar spine and femoral neck Z value in PMOP women with ERα PvuII, 4 studies [11, 20, 33, 38] and 3 studies [20, 33, 38] were included in our meta-analysis, respectively. In addition, all these studies complied with HWE. The characteristics of the included studies are shown in Tables 1, 2 and 3.
Table 1
General characteristics of studies assciated with postmenopausal osteoporosis risk
Author
Year
Ethnicity
Sample Size
ERα XbaI
 
HWE
Case
Control
Case
Control
X
x
XX
Xx
xx
X
x
XX
Xx
xx
Shang et al.
2016
Asian
198
276
338
58
146
46
6
109
443
10
89
177
0.77
Wang et al.
2015
Asian
72
72
125
19
55
15
2
132
12
62
8
2
0.21
Li et al.
2014
Asian
440
791
254
626
31
192
217
404
1178
48
308
435
0.50
Erdogan et al.
2011
Caucasian
50
30
41
59
7
27
16
28
32
6
16
8
0.70
Jeedigunta et al.
2010
Asian
247
254
253
241
60
133
54
306
202
81
144
29
0.32
Tanriover et al.
2010
Caucasian
50
50
48
52
5
38
7
54
46
12
30
8
0.14
Harsløf et al.
2010
Caucasian
228
225
134
322
19
96
113
164
286
30
104
91
0.97
Musumeci et al.
2009
Caucasian
100
200
130
70
35
60
5
155
245
13
129
58
0.26
Pérez et al.
2008
Caucasian
64
68
48
80
9
30
25
46
90
5
36
27
0.13
Ivanova et al.
2007
Caucasian
220
180
256
184
73
110
37
163
197
25
113
42
0.58
Huang et al.
2006
Asian
66
116
19
113
2
15
49
46
186
4
38
74
0.74
Nam et al.
2005
Asian
6
168
0
12
0
0
6
63
273
6
51
111
0.96
Qin et al.
2004
Asian
244
273
120
368
11
98
135
137
409
13
111
149
0.18
Aerssens et al.
2000
Caucasian
135
239
92
178
14
64
57
175
303
32
111
96
0.99
Author
Year
Ethnicity
Sample Size
ERα PvuII
HWE
Case
Control
Case
Control
P
p
PP
Pp
pp
P
p
PP
Pp
pp
Shang et al.
2016
Asian
198
276
156
240
28
100
70
386
166
138
110
28
0.38
Wang et al.
2015
Asian
60
60
30
90
3
24
33
32
88
3
26
31
0.40
Li et al.
2014
Asian
440
791
368
512
65
238
137
498
1084
69
360
362
0.12
Sonoda et al.
2012
Asian
114
171
118
110
24
70
20
137
205
31
75
65
0.26
Erdogan et al.
2011
Caucasian
50
30
42
58
8
26
16
38
22
10
18
2
0.11
Jeedigunta et al.
2010
Asian
247
254
181
313
50
81
116
232
276
60
112
82
0.08
Tanriover et al.
2010
Caucasian
50
50
39
61
7
25
18
48
52
14
20
16
0.79
Harsløf et al.
2010
Caucasian
228
224
198
258
46
106
76
233
215
63
107
54
0.52
Musumeci et al.
2009
Caucasian
100
200
120
80
30
60
10
186
214
31
124
45
0.53
Pérez et al.
2008
Caucasian
64
68
56
72
11
34
19
58
78
12
34
22
0.86
Ivanova et al.
2007
Caucasian
220
180
226
214
58
110
52
148
212
21
106
53
0.37
Morón et al.
2006
Caucasian
87
175
79
95
17
45
25
171
179
45
81
49
0.33
Huang et al.
2006
Asian
66
116
79
53
23
33
10
68
164
11
46
59
0.64
Nam et al.
2005
Asian
6
168
2
10
1
0
5
130
206
25
80
63
0.96
Qin et al.
2004
Asian
244
273
193
295
40
113
91
223
323
43
137
93
0.52
Aerssens et al.
2000
Caucasian
135
239
120
150
27
66
42
219
259
47
125
67
0.41
Author
Year
Ethnicity
Sample Size
ERα G2014A
HWE
Case
Control
Case
Control
A
G
AA
GA
GG
A
G
AA
GA
GG
Wajanavisit et al.
2015
Asian
99
113
94
104
33
28
38
179
47
72
35
6
0.53
Gómez et al.
2007
Caucasian
70
500
30
110
2
26
42
303
697
40
223
237
0.21
Ongphiphadhanakul et al.
2003
Asian
33
325
23
43
5
13
15
129
521
13
103
209
0.94
Ongphiphadhanakul et al.
2001
Asian
106
122
56
156
8
40
58
37
207
2
33
87
0.57
Author
Year
Ethnicity
Sample Size
ERβ AluI
HWE
Case
Control
Case
Control
A
G
AA
GA
GG
A
G
AA
GA
GG
Shoukry et al.
2015
Caucasian
200
180
223
177
75
73
52
125
235
30
65
85
0.46
Huang et al.
2015
Asian
413
890
678
148
285
108
20
1384
396
541
302
47
0.57
Harsløf et al.
2010
Caucasian
228
224
154
302
26
102
100
186
262
35
116
73
0.32
Morón et al.
2006
Caucasian
88
177
76
100
11
54
23
146
208
34
78
65
0.23
Author
Year
Ethnicity
Sample Size
ERβ RsaI
HWE
Case
Control
Case
Control
A
G
AA
GA
GG
A
G
AA
GA
GG
Shoukry et al.
2015
Caucasian
200
180
52
348
2
48
150
37
323
1
35
144
0.47
Huang et al.
2015
Asian
413
777
329
497
63
203
147
759
795
169
421
187
0.28
Table 2
Characteristics of included studies of lumbar spine BMD, femoral neck BMD, lumbar spine Z value and femoral neck Z value in ERα XbaI genotypes
ERα XbaI
Lumbar Spine BMD (g/cm2)
ERα XbaI
Femoral Neck BMD (g/cm2)
XX
Xx
xx
XX
Xx
xx
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Ivanova et al.
2007
Caucasian
73
0.75 ± 0.17
110
0.81 ± 0.06
37
0.87 ± 0.07
Ivanova et al.
2007
Caucasian
73
0.69 ± 0.08
110
0.69 ± 0.04
37
0.65 ± 0.03
Albagha et al.
2001
Caucasian
27
0.88 ± 0.03
89
0.88 ± 0.02
90
0.85 ± 0.02
Albagha et al.
2001
Caucasian
27
0.77 ± 0.03
89
0.73 ± 0.01
90
0.72 ± 0.02
Aerssens et al.
2000
Caucasian
14
0.94 ± 0.21
64
0.93 ± 0.22
57
0.88 ± 0.16
Aerssens et al.
2000
Caucasian
14
0.73 ± 0.03
64
0.68 ± 0.09
57
0.70 ± 0.20
Jeedigunta et al.
2010
Asian
60
0.89 ± 0.15
133
0.86 ± 0.13
54
0.64 ± 0.16
Kurt et al.
2012
Caucasian
41
0.79 ± 0.09
94
0.8 ± 0.08
40
0.83 ± 0.10
Kurt et al.
2012
Caucasian
41
0.95 ± 0.12
94
0.92 ± 0.12
40
0.93 ± 0.10
Ge et al.
2006
Asian
37
0.70 ± 0.10
134
0.68 ± 0.07
26
0.67 ± 0.07
Kurabayashi et al.
1999
Asian
1
1.18 ± 0.00
20
0.92 ± 0.04
61
0.92 ± 0.02
Pérez et al.
2008
Caucasian
7
0.59 ± 0.02
36
0.58 ± 0.01
20
0.56 ± 0.02
Ge et al.
2006
Asian
37
0.73 ± 0.08
134
0.74 ± 0.09
26
0.75 ± 0.13
         
Pérez et al.
2008
Caucasian
7
0.70 ± 0.02
31
0.67 ± 0.02
24
0.66 ± 0.02
         
ERα XbaI
Lumbar Spine Z value
ERα XbaI
Femoral Neck Z value
XX
Xx
xx
XX
Xx
xx
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Shang et al.
2016
Asian
146
−1.98 ± 0.91
146
−1.65 ± 0.02
6
−0.35 ± 2.19
Ivanova et al.
2007
Caucasian
73
−2.00 ± 0.00
110
−2.00 ± 0.00
37
−1.90 ± 0.00
Ivanova et al.
2007
Caucasian
73
−2.10 ± 0.00
110
−0.6 ± 0.00
37
−0.1 ± 0.00
Albagha et al.
2001
Caucasian
27
−2.00 ± 0.23
89
−0.42 ± 0.10
90
−0.52 ± 0.12
Albagha et al.
2001
Caucasian
27
−0.34 ± 0.20
89
−0.29 ± 0.11
90
−0.47 ± 0.11
An et al.
2000
Asian
10
0.42 ± 0.57
84
0.11 ± 0.66
152
−0.32 ± 0.76
An et al.
2000
Asian
10
0.48 ± 0.49
84
0.12 ± 0.85
152
−0.26 ± 0.58
         
Table 3
Characteristics of included studies of lumbar spine BMD, femoral neck BMD, lumbar spine Z value and femoral neck Z value in ERα PvuII genotypes
ERα PvuII
Lumbar Spine BMD (g/cm2)
ERα PvuII
Femoral Neck BMD (g/cm2)
PP
Pp
pp
PP
Pp
pp
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Ivanova et al.
2007
Caucasian
58
0.70 ± 0.09
110
0.71 ± 0.10
52
0.77 ± 0.06
Ivanova et al.
2007
Caucasian
58
0.52 ± 0.02
110
0.68 ± 0.01
52
0.76 ± 0.05
Albagha et al.
2001
Caucasian
37
0.87 ± 0.03
102
0.86 ± 0.02
67
0.88 ± 0.02
Albagha et al.
2001
Caucasian
37
0.75 ± 0.02
102
0.71 ± 0.01
67
0.75 ± 0.02
Aerssens et al.
2000
Caucasian
27
0.93 ± 0.18
66
0.91 ± 0.22
42
0.89 ± 0.17
Aerssens et al.
2000
Caucasian
27
0.69 ± 0.06
66
0.70 ± 0.09
42
0.69 ± 0.11
Jeedigunta et al.
2010
Asian
50
0.92 ± 0.18
81
0.89 ± 0.11
116
0.81 ± 0.14
Kurt et al.
2012
Caucasian
44
0.77 ± 0.08
104
0.81 ± 0.09
46
0.82 ± 0.09
Kurt et al.
2012
Caucasian
44
0.93 ± 0.13
104
0.93 ± 0.11
46
0.93 ± 0.09
Ge et al.
2006
Asian
38
0.68 ± 0.09
93
0.67 ± 0.07
67
0.69 ± 0.08
Kurabayashi et al.
1999
Asian
19
0.99 ± 0.04
27
0.89 ± 0.03
36
0.91 ± 0.02
Ge et al.
2006
Asian
38
0.68 ± 0.09
92
0.67 ± 0.08
67
0.69 ± 0.08
Ge et al.
2006
Asian
38
0.73 ± 0.10
93
0.74 ± 0.09
67
0.75 ± 0.10
Qin et al.
2004
Asian
40
0.57 ± 0.01
113
0.60 ± 0.01
91
0.59 ± 0.01
Ge et al.
2006
Asian
38
0.73 ± 0.10
92
0.74 ± 0.09
67
0.75 ± 0.10
Pérez et al.
2008
Caucasian
9
0.59 ± 0.01
37
0.57 ± 0.01
16
0.57 ± 0.02
Qin et al.
2004
Asian
40
0.70 ± 0.01
113
0.70 ± 0.01
91
0.72 ± 0.01
         
Pérez et al.
2008
Caucasian
11
0.73 ± 0.03
34
0.66 ± 0.02
17
0.65 ± 0.02
         
ERα PvuII
Lumbar Spine Z value
ERα PvuII
Femoral Neck Z value
PP
Pp
pp
PP
Pp
pp
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Author
Year
Ethnicity
N
Mean ± SD
N
Mean ± SD
N
Mean ± SD
Shang et al.
2016
Asian
28
−1.54 ± 0.35
100
−1.67 ± 0.91
70
−2.79 ± 1.46
Ivanova et al.
2007
Caucasian
58
−2.00 ± 0.00
110
−1.90 ± 0.00
52
−0.70 ± 0.00
Ivanova et al.
2007
Caucasian
58
−2.40 ± 0.00
110
−2.10 ± 0.00
52
−1.50 ± 0.00
Albagha et al.
2001
Caucasian
37
−0.29 ± 0.17
102
−0.59 ± 0.09
67
−0.28 ± 0.15
Albagha et al.
2001
Caucasian
37
−0.35 ± 0.16
102
−0.44 ± 0.10
67
−0.28 ± 0.14
An et al.
2000
Asian
53
−0.48 ± 0.90
128
−0.19 ± 0.80
128
0.31 ± 0.49
An et al.
2000
Asian
53
−0.53 ± 0.16
128
−0.21 ± 0.99
65
0.22 ± 0.46
         

Power analysis

Before initiation of the meta-analysis, a power analysis was conducted by using the Power and Precision V4 software to verify whether the included studies could offer adequate power (> 80%). The result showed that the statistical power in our study was sufficient to detect the associations between ER gene polymorphisms and PMOP risk.

Associations between ER gene polymorphisms and PMOP risk

Overall, we did not find any significant association between ERα XbaI and ERα PvuII polymorphisms and risk of PMOP in either overall, Caucasian or Asian populations (all P > 0.05) (Table 4). ERα G2014A polymorphism played a protcetive role in developing PMOP in Caucasian populations, while no significant association was observed in overall and Asian populations (both P > 0.05). All the data are shown in Table 4 and Fig. 2.
Table 4
Results of genetic models for ERα XbaI, ERα PvuII, ERα G2014A, ERβ AluI and ERβ RsaI polymorphisms and osteoporosis susceptibility in postmenopausal women
Comparison
N
Test of association
Model
Test of heterogeneity
Begg’s test
Egger’s test
OR
95% CI
P value
P value
I2 (%)
P value
P value
ERα XbaI
Overall
14
        
 X vs. x
 
1.21
0.73–2.00
0.455
R
< 0.001
96.4
0.584
0.955
 XX vs. xx
 
1.84
0.71–4.75
0.206
R
< 0.001
93.7
0.443
0.465
 Xx vs. xx
 
1.19
0.83–1.70
0.357
R
< 0.001
80.1
0.511
0.610
 Xx/XX vs. xx
 
1.34
0.82–2.18
0.240
R
< 0.001
90.4
0.661
0.545
 XX vs. Xx/xx
 
1.50
0.70–3.24
0.296
R
< 0.001
93.4
0.443
0.875
Caucasian
7
        
 X vs. x
 
1.15
0.76–1.74
0.510
R
< 0.001
88.0
  
 XX vs. xx
 
1.56
0.56–4.39
0.399
R
< 0.001
88.9
  
 Xx vs. xx
 
1.13
0.76–1.67
0.540
R
0.021
59.8
  
 Xx/XX vs. xx
 
1.24
0.76–2.01
0.387
R
< 0.001
76.2
  
 XX vs. Xx/xx
 
1.30
0.56–3.03
0.536
R
< 0.001
88.2
  
Asian
7
        
 X vs. x
 
1.23
0.47–3.25
0.668
R
< 0.001
98.0
  
 XX vs. xx
 
2.18
0.37–12.73
0.388
R
< 0.001
98.1
  
 Xx vs. xx
 
1.22
0.63–2.36
0.553
R
< 0.001
88.0
  
 Xx/XX vs. xx
 
1.39
0.56–3.46
0.481
R
< 0.001
94.6
  
 XX vs. Xx/xx
 
1.77
0.44–7.14
0.424
R
< 0.001
96.0
  
ERα PvuII
Overall
16
        
 P vs. p
 
0.96
0.71–1.29
0.769
R
< 0.001
92.3
0.753
0.616
 PP vs. pp
 
0.99
0.55–1.78
0.961
R
< 0.001
90.8
1.000
0.886
 Pp vs. pp
 
1.01
0.72–1.41
0.956
R
< 0.001
82.3
0.753
0.501
 PP/Pp vs. pp
 
0.97
0.65–1.43
0.868
R
< 0.001
88.7
0.893
0.539
 PP vs. Pp/pp
 
0.99
0.65–1.53
0.977
R
< 0.001
87.3
0.893
0.976
Caucasian
8
        
 P vs. p
 
0.95
0.71–1.26
0.716
R
< 0.001
79.2
  
 PP vs. pp
 
0.93
0.49–1.79
0.831
R
< 0.001
81.4
  
 Pp vs. pp
 
0.98
0.73–1.31
0.877
R
0.112
40.0
  
 PP/Pp vs. pp
 
0.97
0.67–1.39
0.861
R
0.008
63.5
  
 PP vs. Pp/pp
 
0.97
0.59–1.58
0.895
R
< 0.001
78.2
  
Asian
8
        
 P vs. p
 
0.97
0.57–1.66
0.919
R
< 0.001
95.6
  
 PP vs. pp
 
1.08
0.40–2.96
0.877
R
< 0.001
94.4
  
 Pp vs. pp
 
1.04
0.58–1.88
0.889
R
< 0.001
90.2
  
 PP/Pp vs. pp
 
0.98
0.50–1.95
0.962
R
< 0.001
93.8
  
 PP vs. Pp/pp
 
1.05
0.50–2.20
0.891
R
< 0.001
91.8
  
 ERα G2014A
Overall
4
        
 A vs. G
 
0.89
0.32–2.51
0.825
R
< 0.001
95.1
0.308
0.237
 AA vs. GG
 
0.88
0.08–9.19
0.912
R
< 0.001
92.9
0.734
0.419
 GA vs. GG
 
0.76
0.28–2.03
0.581
R
< 0.001
88.1
0.734
0.530
 GA/AA vs. GG
 
0.73
0.22–2.41
0.601
R
< 0.001
92.8
0.734
0.530
 AA vs. GA/GG
 
1.13
0.23–5.72
0.878
R
< 0.001
88.6
0.734
0.299
Caucasian
1
        
 A vs. G
 
0.63
0.41–0.96
0.032
R
  
 AA vs. GG
 
0.28
0.07–1.21
0.089
R
  
 GA vs. GG
 
0.66
0.39–1.11
0.116
R
  
 GA/AA vs. GG
 
0.60
0.36–1.00
0.050
R
  
 AA vs. GA/GG
 
0.34
0.08–1.43
0.141
R
  
Asian
3
        
 A vs. G
 
1.00
0.23–4.46
0.996
R
< 0.001
96.6
  
 AA vs. GG
 
1.28
0.05–30.10
0.878
R
< 0.001
95.2
  
 GA vs. GG
 
0.77
0.17–3.45
0.736
R
< 0.001
91.3
  
 GA/AA vs. GG
 
0.76
0.12–4.62
0.765
R
< 0.001
94.8
  
 AA vs. GA/GG
 
1.69
0.20–14.27
0.630
R
< 0.001
92.2
  
ERβ AluI
Overall
4
        
 A vs. G
 
1.25
0.78–2.00
0.362
R
< 0.001
91.5
1.000
0.997
 AA vs. GG
 
1.27
0.52–3.13
0.597
R
< 0.001
88.4
0.734
0.647
 GA vs. GG
 
1.16
0.65–2.07
0.606
R
0.001
81.0
0.734
0.408
 GA/AA vs. GG
 
1.29
0.66–2.53
0.459
R
< 0.001
87.8
0.734
0.612
 AA vs. GA/GG
 
1.21
0.65–2.24
0.553
R
< 0.001
85.7
0.497
0.646
Caucasian
3
        
 A vs. G
 
1.23
0.58–2.57
0.590
R
< 0.001
94.3
  
 AA vs. GG
 
1.28
0.34–4.84
0.717
R
< 0.001
92.2
  
 GA vs. GG
 
1.30
0.60–2.78
0.504
R
0.001
86.5
  
 GA/AA vs. GG
 
1.36
0.55–3.39
0.507
R
< 0.001
91.8
  
 AA vs. GA/GG
 
1.10
0.37–3.22
0.863
R
< 0.001
90.3
  
Asian
1
        
 A vs. G
 
1.31
1.06–1.62
0.012
R
  
 AA vs. GG
 
1.24
0.72–2.13
0.441
R
  
 GA vs. GG
 
0.84
0.48–1.48
0.548
R
  
 GA/AA vs. GG
 
1.10
0.64–1.87
0.739
R
  
 AA vs. GA/GG
 
1.44
1.12–1.84
0.004
R
  
ERβ RsaI
Overall
2
        
 A vs. G
 
0.92
0.50–1.70
0.785
R
0.010
85.0
  
 AA vs. GG
 
0.49
0.34–0.70
< 0.001
F
0.261
20.9
  
 GA vs. GG
 
0.87
0.41–1.84
0.722
R
< 0.001
85.9
  
 GA/AA vs. GG
 
0.85
0.37–1.95
0.704
R
< 0.001
88.9
  
 AA vs. GA/GG
 
0.66
0.48–0.90
0.009
F
0.408
0
  
Caucasian
1
        
 A vs. G
 
1.30
0.83–2.04
0.245
R
  
 AA vs. GG
 
1.92
0.17–21.41
0.596
F
  
 GA vs. GG
 
1.32
0.80–2.15
0.273
R
  
 GA/AA vs. GG
 
1.33
0.82–2.17
0.246
R
  
 AA vs. GA/GG
 
1.81
0.16–20.11
0.630
F
  
Asian
1
        
 A vs. G
 
0.69
0.58–0.82
< 0.001
R
  
 AA vs. GG
 
0.47
0.33–0.68
< 0.001
F
  
 GA vs. GG
 
0.61
0.47–0.81
< 0.001
R
  
 GA/AA vs. GG
 
0.57
0.44–0.74
< 0.001
R
  
 AA vs. GA/GG
 
0.65
0.47–0.89
0.007
F
  
R Random effect model
F Fixed effect model
With regard to ERβ polymorphism, ERβ AluI was significantly associated with the risk of developing PMOP in Asian postmenopausal women under the recessive model; however, we did not observe any significant association between ERβ AluI and PMOP risk in overall and Caucasian populations (both P > 0.05) (Table 4 and Fig. 3). Furthermore, we also found that there was a remarkable association between ERβ RsaI polymorphism and decreased PMOP risk in overall and Asian populations (Table 4).

Associations between ER gene polymorphisms and BMD in PMOP women

ERα XbaI and lumbar spine bone mineral density (BMD g/cm2 and BMD Z value)

In our meta-analysis, no significant difference in lumbar spine BMD (g/cm2) was observed between PMOP women with ERα XbaI XX, ERα XbaI Xx and ERα XbaI xx genotype in either overall, Caucasian or Asian populations (all P > 0.05) (Table 5). The lumbar spine BMD Z value in Caucasian PMOP women carrying ERα XbaI XX genotype was greater than that in those carrying xx genotype, while no significant difference was observed in overall and Asian populations (both P > 0.05). ERα XbaI Xx genotype was found to be significantly associated with high lumbar spine BMD Z value in either overall or Caucasian populations but not in Asian populations.
Table 5
Meta-analysis of differences of Lumbar Spine BMD, Femoral Neck BMD, Lumbar Spine Z value and Femoral Neck Z value between each genotype of ERα XbaI and ERα PvuII polymorphism
ERα XbaI
XX vs. xx
Xx vs. xx
Test of differences
Model
Test of heterogeneity
Test of differences
Model
Test of heterogeneity
N
WMD (95% CI)
P value
P value
I2 (%)
N
WMD (95% CI)
P value
P value
I2 (%)
Lumbar Spine BMD (g/cm2)
 Overall
8
0.03 (−0.02, 0.08)
0.198
R
< 0.001
94.2
8
0.02 (− 0.00, 0.05)
0.086
R
< 0.001
94.1
 Caucasian
5
0.00 (−0.04, 0.04)
0.917
R
< 0.001
90.2
5
0.00 (−0.02, 0.02)
0.862
R
< 0.001
91.1
 Asian
3
0.11 (−0.16, 0.38)
0.414
R
< 0.001
97.8
3
0.07 (−0.07, 0.20)
0.326
R
< 0.001
97.3
Lumbar Spine Z value
 Overall
3
0.22 (−0.40, 0.83)
0.495
R
< 0.001
88.5
3
0.24 (0.00, 0.47)
0.046
R
0.041
68.6
 Caucasian
1
0.13 (0.05, 0.21)
0.001
R
1
0.18 (0.15, 0.21)
< 0.001
R
 Asian
2
−0.28 (−2.58, 2.02)
0.811
R
0.009
85.2
2
−0.23 (− 1.81, 1.36)
0.780
R
0.062
71.3
Femoral Neck BMD (g/cm2)
 Overall
6
0.03 (0.01, 0.05)
0.003
R
0.001
75.5
6
0.01 (−0.00, 0.03)
0.057
R
< 0.001
84.7
 Caucasian
5
0.03 (0.01, 0.05)
0.009
R
< 0.001
80.4
5
0.01 (−0.00, 0.03)
0.094
R
< 0.001
87.7
 Asian
1
0.03 (−0.01, 0.08)
0.110
R
1
0.01 (−0.02, 0.04)
0.350
R
Femoral Neck Z value
 Overall
2
−0.38 (−2.56, 1.80)
0.733
R
< 0.001
99.2
2
0.25 (−0.07, 0.58)
0.130
R
0.001
91.6
 Caucasian
1
−1.48 (−1.57, −1.39)
< 0.001
R
1
0.10 (0.07, 0.13)
< 0.001
R
 Asian
1
0.74 (0.37, 1.11)
< 0.001
R
1
0.43 (0.24, 0.62)
< 0.001
R
ERα PvuII
PP vs. pp
Pp vs. pp
Test of differences
Model
Test of heterogeneity
Test of differences
Model
Test of heterogeneity
N
WMD (95% CI)
P value
P value
I2 (%)
N
WMD (95% CI)
P value
P value
I2 (%)
Lumbar Spine BMD (g/cm2)
 Overall
10
0.02 (− 0.01, 0.04)
0.216
R
< 0.001
95.5
10
−0.01 (− 0.02, − 0.00)
0.036
R
< 0.001
84.0
 Caucasian
5
0.01 (−0.04, 0.06)
0.793
R
< 0.001
95.5
5
−0.02 (− 0.03, 0.00)
0.106
R
< 0.001
84.9
 Asian
5
0.03 (−0.02, 0.08)
0.288
R
< 0.001
96.2
5
−0.00 (− 0.02, 0.02)
0.912
R
< 0.001
86.4
Lumbar Spine Z value
 Overall
3
0.11 (−0.55, 0.78)
0.742
R
< 0.001
98.7
3
0.13 (−0.40, 0.67)
0.623
R
< 0.001
95.9
 Caucasian
1
−0.07 (− 0.13, − 0.01)
0.031
R
1
− 0.16 (− 0.20, − 0.12)
< 0.001
R
 Asian
2
0.24 (−1.72, 2.20)
0.809
R
< 0.001
99.0
2
0.34 (−1.18, 1.85)
0.665
R
< 0.001
97.9
Femoral Neck BMD (g/cm2)
 Overall
8
−0.04 (− 0.09, 0.01)
0.135
R
< 0.001
99.3
8
−0.02 (− 0.04, 0.01)
0.132
R
< 0.001
98.2
 Caucasian
5
−0.06 (− 0.16, 0.05)
0.295
R
< 0.001
99.6
5
−0.03 (− 0.05, 0.00)
0.054
R
< 0.001
95.2
 Asian
3
−0.01 (− 0.02, − 0.01)
< 0.001
R
1.000
0.00
3
−0.00 (− 0.03, 0.02)
0.768
R
0.009
78.7
Femoral Neck Z value
 Overall
2
−0.39 (−1.15, 0.37)
0.315
R
< 0.001
97.0
2
−0.39 (− 0.57, − 0.20)
< 0.001
R
0.024
80.3
 Caucasian
1
−0.01 (− 0.08, 0.05)
0.718
R
1
−0.31 (− 0.35, − 0.27)
< 0.001
R
 Asian
1
−0.79 (−1.05, − 0.53)
< 0.001
R
1
− 0.50 (− 0.66, − 0.34)
< 0.001
R
R Random effect model
F Fixed effect model

ERα XbaI and femoral neck bone mineral density (BMD g/cm2 and BMD Z value)

Our pooled analyses indicated that the ERα XbaI XX genotype was significantly associated with increased femoral neck BMD in overall and Caucasian populations. In contrast, ERα XbaI XX genotype did not play a key role in femoral neck BMD in Asian populations (Table 5 and Fig. 4). Interestingly, compared with PMOP women with xx genotype, XX genotype was significantly associated with decreased femoral neck Z value in Caucasians, and increased femoral neck Z value in Asians (Table 5). However, no significant association was observed between XX genotype and the femoral neck Z value in overall populations. In addition, Caucasians and Asians carrying the ERα XbaI Xx genotype were at risk of a high femoral neck Z value, while no significant association was found in overall populations. We did not observe remarkable relationships between ERα XbaI Xx genotype and femoral neck BMD in either overall, Caucasian or Asian populations (all P > 0.05). All data are shown in Table 5.

ERα PvuII and lumbar spine bone mineral density (BMD g/cm2 and BMD Z value)

With regard to ERα PvuII, the difference in the lumbar spine Z value between the PP and pp. genotypes was − 0.07 (95% CI = − 0.03 to − 0.01, P = 0.031) in Caucasian PMOP women; however, no significant difference was observed in overall and Asian populations. For the Pp versus pp. genotype, the difference in lumbar spine BMD was − 0.01 (95% CI = − 0.02 to − 0.00, P = 0.036) in overall populations, and the difference in the lumbar spine Z value was − 0.16 (95% CI = − 0.20 to − 0.12, P < 0.001) in Caucasian populations; however, we did not find any significant difference in lumbar spine BMD in either Caucasians or Asians, and in the lumbar spine Z value in overall and Asian populations (Table 5 and Fig. 5). In addition, no significant difference in lumbar spine BMD was observed between PP and pp. genotypes (P > 0.05) (Table 5).

ERα PvuII and femoral neck bone mineral density (BMD g/cm2 and BMD Z value)

We further found that the ERα PvuII PP genotype was associated with decreased femoral neck BMD and Z value compared with the pp. genotype in Asians, while no significant difference in femoral neck BMD and Z value was observed in either overall and Caucasian populations (both P > 0.05) (Table 5). Furthrmore, PMOP women carrying the Pp genotype were at risk of a low femoral neck Z value, which was found in overall, Caucasian and Asian populations. Our study showed that there was no significant difference in femoral neck BMD between PMOP women with the Pp genotype and those with the pp. genotype (P > 0.05). All the data are shown in Table 5.

Sensitivity analysis and publication bias

We performed a leave-one-out analysis to estimate the sensitivity of our study and found that omission of any single study did not affect the overall statistical significance, indicating that the results of our meta-analysis are stable. Therefore, we could conclude that our meta-analysis data are relatively stable and credible. To estimate the publication bias of our meta-analysis, the Begg’s and Egger’s test was performed (Table 4), indicating that there was minimal evidence of publication bias. The shape of funnel plot was symmetrical, which also showed no publication bias in our study (Fig. 6).

Discussion

Associations between ERα gene polymorphisms and PMOP risk

ERα XbaI and ERα PvuII are the two restriction fragment length polymorphisms of ERα gene located in Intron 1 [14]. Many studies [1125, 32] have been performed to explore the relationships between ERα XbaI, ERα PvuII and PMOP risk; however, these studies have yielded inconsistent data [1125, 32]. Overall, we did not observe any significant association between ERα XbaI and ERα PvuII polymorphisms and PMOP risk in either overall, Caucasian or Asian populations. In our opinion, the inadequate sample size, different ethnicities, various genotyping techniques, the presence of admixture in the population, gene-environment interactions, differences in age and measurement errors of different investigators might be important factors contributing to these controversial results. ERα XbaI and ERα PvuII have proven to play key roles in attainment and maintenance of peek bone mass during young adulthood, and it might be difficult to document their effects in a population of postmenopausal women [24]. In addition, PvuII and XbaI polymorphisms are located in a non-functional area of the ER gene [20], which might also contribute to our polled results. With regard to ERα G2014A, it is located on the exon region of chromosome 6p25.1, and may contribute via the epigenetic level for the efficiency of translation or receptor protein expression [26]. Our results showed that a significant association between ERα G2014A and PMOP risk was observed only in Caucasian populations but not in overall and Asian populations.

Associations between ERβ gene polymorphisms and PMOP risk

ERβ has been found to be more abundant than ERα in trabecular bone, and more potent than ERα in mediating estrogen-induced repression of TNF-α expression, which is considered an important contributor to PMOP [30]. ERβ AluI is one of the widely-studied ERβ gene polymorphisms, knowing that it could alter mRNA stability and protein levels, leading to reduced synthesis of ERβ [30]. In our study, ERβ AluI was found to be significantly associated with increased risk of PMOP in Asian populations, while no significant relationship was observed in overall and Caucasian populations. Thus, different genetic backgrounds, environmental effects and/or their internal interactions could explain the diverse results in various ethnicities. ERβ RsaI is another important polymorphism of ERβ. Our subgroup analysis revealed a significant association between ERβ RsaI and PMOP risk in overall populations, which is consistent with the studies of Shoukry et al. [30], and Huang et al. [31].

Associations between ERα XbaI and lumbar spine and femoral neck BMD

Our pooled results showed that there was no significant difference in lumbar spine BMD between PMOP women carrying XX, Xx and xx genotype in either overall, Caucasian or Asian populations. However, WANG et al. [39] reported that the XbaI polymorphism was significantly associated with BMD of the lumbar spine, and XX had a protective effect in comparison with carriers of the x alleles, which is consistent with the report of Ioannidis et al. [41]. Both WANG and Ioannidis included all types of osteoporotic patients, not only postmenopausal women, which might be the most important reason for the difference between our results and theirs. As mentioned above, ERα XbaI might not play a key role in attainment and maintenance of peek bone mass in postmenopausal women [24], and therefore it could be easily understood why no significant association was observed between ERα XbaI and lumbar spine BMD. With regard to femoral neck BMD, our study indicated that the femoral neck BMD in PMOP women with XX genotype was significantly higher than that in women with xx genotype in overall and Caucasian populations, which highlights the theory that ERα gene is involved in the pathogenesis of PMOP. No significant difference of femoral neck BMD was observed between PMOP women with Xx and xx genotype in each subgroup. Although no significant association was observed between lumbar spine BMD and ERα XbaI, we found that the lumbar spine Z value in both PMOP women carrying XX and those carrying Xx genotype was significantly higher than that in Caucasians carrying xx genotype. We also observed that XX genotype was associated with a low femoral neck Z value in Caucasians and high femoral neck Z value in Asians. In addition, Caucasians and Asians carrying Xx genotype were at risk of a high femoral neck Z value. However, why ERα XbaI plays a contradictory role in BMD and Z value at the lumar spine and femoral neck, and the mechanisms by which it is associated with BMD and Z value remains unclear and needs further investigation.

Associations between ERα PvuII and lumbar spine and femoral neck BMD

Although the molecular mechanism underlying the effect of ERα PvuII on bone mass is poorly understood, it is believed that ERα PvuII might play a key role in BMD as it is in linkage disequilibrium with the TA polymorphism in the ER promoter that is associated with altered gene transcription [20]. Our pooled analysis indicated that PMOP women with the Pp genotype had lower lumbar spine BMD than those with the pp. genotype. We also found that there was no significant difference in lumbar spine BMD between women with the PP genotype and those with the pp. genotype, which is consistent with the meta-analysis of Wang et al. [40]. Furthermore, we observed that the PP genotype was associated with decreased femoral neck BMD in Asians, while Pp might not play a key role in femoral neck BMD in all subgroups. Interestingly, WANG et al. [39] reported that PP play a role in protecting the lumbar spine but on the other hand it might be a risk factor for the femoral neck fracture. Wang CL [40] and WANG KJ [39] conducted their meta-analyses on osteoporotic women during menopause while our study included osteoporotic women post menopause, which might be the most important reason for the difference between our study and theirs. In addition, both PP and Pp genotypes were significantly associated with low lumbar spine Z value in Caucasians, but not in overall and Asian populations, probably because of the different genetic backgrounds in various ethnicities and interactions between genetic and non-genetic factors. PMOP women with the PP and Pp genotypes had lower femoral neck Z value than those with the pp. genotype in overall, Caucasian and Asian populations.

Limitations

Although we performed a comprehensive analysis of the association between ERα, ERβ gene polymorphisms and PMOP risk and BMD in postmenopausal women, there are some limitations that should be addressed. First, high heterogeneity was observed in some of our pooled results, which might have negative impact on our conclusions. Second, PMOP is a disease whose etiology might be involved in several confounding factors, and other confounding factors such as age, years since menopause and estrogen therapy might interact with each other and play a key role in the etiology and progression of PMOP. However, no data available could be used in all recruited studies to detect the interactions between these confounding factors in PMOP patients. We should take all these confounding factors into consideration in our study rather than studying them separately, which is also a limitation of our meta-analysis. Third, we failed to perform a pooled analysis to detect whether ERα G2014A, ERβ AluI and ERβ RsaI were correlated with BMD in postmenopausal women as no sufficient data could be collected and analyzed. Therefore, larger-scale and better-designed studies are necessary to determine the association between ERα/β gene polymorphisms and PMOP risk and BMD in postmenopausal women.

Conclusion

ERα/β gene polymorphisms were significantly associated with PMOP risk and BMD in postmenopausal women, but each ERα/β gene polymorphism may have a distinct effect on PMOP risk and BMD in Asian and Caucasian populations.

Acknowledgements

Not applicable

Funding

No

Availability of data and materials

In publicly available repositories
Not applicable
Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Literatur
1.
Zurück zum Zitat Gokosmanoglu F, Varim C, Atmaca A, Atmaca MH, Colak R. The effects of zoledronic acid treatment on depression and quality of life in women with postmenopausal osteoporosis: a clinical trial study. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2016;21:112.CrossRef Gokosmanoglu F, Varim C, Atmaca A, Atmaca MH, Colak R. The effects of zoledronic acid treatment on depression and quality of life in women with postmenopausal osteoporosis: a clinical trial study. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2016;21:112.CrossRef
2.
Zurück zum Zitat Bandeira L, Bilezikian JP. Novel therapies for postmenopausal osteoporosis. Endocrinol Metab Clin N Am. 2017;46(1):207–19.CrossRef Bandeira L, Bilezikian JP. Novel therapies for postmenopausal osteoporosis. Endocrinol Metab Clin N Am. 2017;46(1):207–19.CrossRef
3.
Zurück zum Zitat Eastell R, O'Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT, Cummings SR. Postmenopausal osteoporosis. Nature reviews Disease primers. 2016;2:16069.CrossRefPubMed Eastell R, O'Neill TW, Hofbauer LC, Langdahl B, Reid IR, Gold DT, Cummings SR. Postmenopausal osteoporosis. Nature reviews Disease primers. 2016;2:16069.CrossRefPubMed
4.
Zurück zum Zitat Wensel TM, Iranikhah MM, Wilborn TW. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. Pharmacotherapy. 2011;31(5):510–23.CrossRefPubMed Wensel TM, Iranikhah MM, Wilborn TW. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. Pharmacotherapy. 2011;31(5):510–23.CrossRefPubMed
5.
Zurück zum Zitat Paschalis EP, Gamsjaeger S, Hassler N, Fahrleitner-Pammer A, Dobnig H, Stepan JJ, Pavo I, Eriksen EF, Klaushofer K. Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. Bone. 2017;95:41–6.CrossRefPubMed Paschalis EP, Gamsjaeger S, Hassler N, Fahrleitner-Pammer A, Dobnig H, Stepan JJ, Pavo I, Eriksen EF, Klaushofer K. Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. Bone. 2017;95:41–6.CrossRefPubMed
6.
Zurück zum Zitat Ebina K, Kashii M, Hirao M, Hashimoto J, Noguchi T, Koizumi K, Kitaguchi K, Matsuoka H, Iwahashi T, Tsukamoto Y, et al. Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis. J Bone Miner Metab. 2016; Ebina K, Kashii M, Hirao M, Hashimoto J, Noguchi T, Koizumi K, Kitaguchi K, Matsuoka H, Iwahashi T, Tsukamoto Y, et al. Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis. J Bone Miner Metab. 2016;
7.
Zurück zum Zitat Safer U, Safer VB, Demir SO, Yanikoglu I. Effects of bisphosphonates and calcium plus vitamin-D supplements on cognitive function in postmenopausal osteoporosis section sign. Endocrine, metabolic & immune disorders drug targets. 2016;16(1):56–60.CrossRef Safer U, Safer VB, Demir SO, Yanikoglu I. Effects of bisphosphonates and calcium plus vitamin-D supplements on cognitive function in postmenopausal osteoporosis section sign. Endocrine, metabolic & immune disorders drug targets. 2016;16(1):56–60.CrossRef
8.
Zurück zum Zitat Gennari L, Rotatori S, Bianciardi S, Nuti R, Merlotti D. Treatment needs and current options for postmenopausal osteoporosis. Expert Opin Pharmacother. 2016;17(8):1141–52.CrossRefPubMed Gennari L, Rotatori S, Bianciardi S, Nuti R, Merlotti D. Treatment needs and current options for postmenopausal osteoporosis. Expert Opin Pharmacother. 2016;17(8):1141–52.CrossRefPubMed
9.
Zurück zum Zitat Xie W, Ji L, Zhao T, Gao P. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray. Medical science monitor : international medical journal of experimental and clinical research. 2015;21:1333–44.CrossRef Xie W, Ji L, Zhao T, Gao P. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray. Medical science monitor : international medical journal of experimental and clinical research. 2015;21:1333–44.CrossRef
10.
Zurück zum Zitat Macari S, Ajay Sharma L, Wyatt A, Knowles P, Szawka RE, Garlet GP, Grattan DR, Dias GJ, Silva TA. Osteoprotective effects of estrogen in the maxillary bone depend on ERalpha. J Dent Res. 2016;95(6):689–96.CrossRefPubMed Macari S, Ajay Sharma L, Wyatt A, Knowles P, Szawka RE, Garlet GP, Grattan DR, Dias GJ, Silva TA. Osteoprotective effects of estrogen in the maxillary bone depend on ERalpha. J Dent Res. 2016;95(6):689–96.CrossRefPubMed
11.
Zurück zum Zitat Shang DP, Lian HY, Fu DP, Wu J, Hou SS, Lu JM. Relationship between estrogen receptor 1 gene polymorphisms and postmenopausal osteoporosis of the spine in Chinese women. Genetics and molecular research : GMR. 2016;15(2) Shang DP, Lian HY, Fu DP, Wu J, Hou SS, Lu JM. Relationship between estrogen receptor 1 gene polymorphisms and postmenopausal osteoporosis of the spine in Chinese women. Genetics and molecular research : GMR. 2016;15(2)
12.
Zurück zum Zitat Wang ZR. Age diference of estrogen receptor gene polymorphisms in the elderly women with hip osteoporosis. Chin. J.of Tissue Engmeenng Res. 2015;19(7):991–5. Wang ZR. Age diference of estrogen receptor gene polymorphisms in the elderly women with hip osteoporosis. Chin. J.of Tissue Engmeenng Res. 2015;19(7):991–5.
13.
Zurück zum Zitat Hai L, Jishen X, Bingpu C, Hailing H, Jinhua W, Jianhai C, xiaoyan F. Estrogen receptor- alpha gene PvuII, XbaI polymorphism, camellia oil and post-menopausal osteoporosis relevance in Guangxi Zhuang. Chinese. J Anat. 2014;37(5):581–4. Hai L, Jishen X, Bingpu C, Hailing H, Jinhua W, Jianhai C, xiaoyan F. Estrogen receptor- alpha gene PvuII, XbaI polymorphism, camellia oil and post-menopausal osteoporosis relevance in Guangxi Zhuang. Chinese. J Anat. 2014;37(5):581–4.
14.
Zurück zum Zitat Erdogan MO, Yildiz H, Artan S, Solak M, Tascioglu F, Dundar U, Eser B, Colak E. Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;22(4):1219–25.CrossRef Erdogan MO, Yildiz H, Artan S, Solak M, Tascioglu F, Dundar U, Eser B, Colak E. Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;22(4):1219–25.CrossRef
15.
Zurück zum Zitat Jeedigunta Y, Bhoomi Reddy PR, Kolla VK, Munshi A, Ananthapur V, Narasimulu G, Akka J. Association of estrogen receptor alpha gene polymorphisms with BMD and their affect on estradiol levels in pre- and postmenopausal women in south Indian population from Andhra Pradesh. Clin. Chim. Acta ; Int. J. of clin. Chem. 2010;411(7–8):597–600.CrossRef Jeedigunta Y, Bhoomi Reddy PR, Kolla VK, Munshi A, Ananthapur V, Narasimulu G, Akka J. Association of estrogen receptor alpha gene polymorphisms with BMD and their affect on estradiol levels in pre- and postmenopausal women in south Indian population from Andhra Pradesh. Clin. Chim. Acta ; Int. J. of clin. Chem. 2010;411(7–8):597–600.CrossRef
16.
Zurück zum Zitat Durusu Tanriover M, Bora Tatar G, Uluturk TD, Dayangac Erden D, Tanriover A, Kilicarslan A, Oz SG, Erdem Yurter H, Sozen T, Sain Guven G. Evaluation of the effects of vitamin D receptor and estrogen receptor 1 gene polymorphisms on bone mineral density in postmenopausal women. Clin Rheumatol. 2010;29(11):1285–93.CrossRefPubMed Durusu Tanriover M, Bora Tatar G, Uluturk TD, Dayangac Erden D, Tanriover A, Kilicarslan A, Oz SG, Erdem Yurter H, Sozen T, Sain Guven G. Evaluation of the effects of vitamin D receptor and estrogen receptor 1 gene polymorphisms on bone mineral density in postmenopausal women. Clin Rheumatol. 2010;29(11):1285–93.CrossRefPubMed
17.
Zurück zum Zitat Harslof T, Husted LB, Carstens M, Stenkjaer L, Langdahl BL. Genotypes and haplotypes of the estrogen receptor genes, but not the retinoblastoma-interacting zinc finger protein 1 gene, are associated with osteoporosis. Calcif Tissue Int. 2010;87(1):25–35.CrossRefPubMed Harslof T, Husted LB, Carstens M, Stenkjaer L, Langdahl BL. Genotypes and haplotypes of the estrogen receptor genes, but not the retinoblastoma-interacting zinc finger protein 1 gene, are associated with osteoporosis. Calcif Tissue Int. 2010;87(1):25–35.CrossRefPubMed
18.
Zurück zum Zitat Musumeci M, Vadala G, Tringali G, Insirello E, Roccazzello AM, Simpore J, Musumeci S. Genetic and environmental factors in human osteoporosis from sub-Saharan to Mediterranean areas. J Bone Miner Metab. 2009;27(4):424–34.CrossRefPubMed Musumeci M, Vadala G, Tringali G, Insirello E, Roccazzello AM, Simpore J, Musumeci S. Genetic and environmental factors in human osteoporosis from sub-Saharan to Mediterranean areas. J Bone Miner Metab. 2009;27(4):424–34.CrossRefPubMed
19.
Zurück zum Zitat Perez A, Ulla M, Garcia B, Lavezzo M, Elias E, Binci M, Rivoira M, Centeno V, Alisio A, Tolosa de Talamoni N. Genotypes and clinical aspects associated with bone mineral density in argentine postmenopausal women. J Bone Miner Metab. 2008;26(4):358–65.CrossRefPubMed Perez A, Ulla M, Garcia B, Lavezzo M, Elias E, Binci M, Rivoira M, Centeno V, Alisio A, Tolosa de Talamoni N. Genotypes and clinical aspects associated with bone mineral density in argentine postmenopausal women. J Bone Miner Metab. 2008;26(4):358–65.CrossRefPubMed
20.
Zurück zum Zitat Ivanova JT, Doukova PB, Boyanov MA, Popivanov PR. PvuII and XbaI polymorphisms of the estrogen receptor gene and bone mineral density in a Bulgarian population sample. Hormones (Athens, Greece). 2007;6(1):36–43. Ivanova JT, Doukova PB, Boyanov MA, Popivanov PR. PvuII and XbaI polymorphisms of the estrogen receptor gene and bone mineral density in a Bulgarian population sample. Hormones (Athens, Greece). 2007;6(1):36–43.
21.
Zurück zum Zitat Wang W, Fu SJ, Wang XS, Zhang YP, Wang SW, Zhong B. The relationship between ER gene polymorphisms and postmenopause osteoporosis of spine in southern Chinese women. Jurnal of Clinical Orthopsedics. 2006;9(6):562–5. Wang W, Fu SJ, Wang XS, Zhang YP, Wang SW, Zhong B. The relationship between ER gene polymorphisms and postmenopause osteoporosis of spine in southern Chinese women. Jurnal of Clinical Orthopsedics. 2006;9(6):562–5.
22.
Zurück zum Zitat Nam HS, Shin MH, Kweon SS, Park KS, Sohn SJ, Rhee JA, Choi JS, Son MH. Association of estrogen receptor-alpha gene polymorphisms with bone mineral density in postmenopausal Korean women. J Bone Miner Metab. 2005;23(1):84–9.CrossRefPubMed Nam HS, Shin MH, Kweon SS, Park KS, Sohn SJ, Rhee JA, Choi JS, Son MH. Association of estrogen receptor-alpha gene polymorphisms with bone mineral density in postmenopausal Korean women. J Bone Miner Metab. 2005;23(1):84–9.CrossRefPubMed
23.
Zurück zum Zitat Qin YJ, Zhang ZL, Huang QR, He JW, Zhou Q, Hu YQ, Li M, Liu YJ. Association of ER alpha gene PvuII and XbaI polymorphisms and related factors with osteoporosis in postmenopausal women: a case-control study. Chin J Geriatr. 2004;23(6):380–3. Qin YJ, Zhang ZL, Huang QR, He JW, Zhou Q, Hu YQ, Li M, Liu YJ. Association of ER alpha gene PvuII and XbaI polymorphisms and related factors with osteoporosis in postmenopausal women: a case-control study. Chin J Geriatr. 2004;23(6):380–3.
24.
Zurück zum Zitat Aerssens J, Dequeker J, Peeters J, Breemans S, Broos P, Boonen S. Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2000;11(7):583–91.CrossRef Aerssens J, Dequeker J, Peeters J, Breemans S, Broos P, Boonen S. Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2000;11(7):583–91.CrossRef
25.
Zurück zum Zitat Sonoda T, Takada J, Iba K, Asakura S, Yamashita T, Mori M. Interaction between ESRα polymorphisms and environmental factors in osteoporosis. J Orthop Res. 2012;30(10):1529–34.CrossRefPubMed Sonoda T, Takada J, Iba K, Asakura S, Yamashita T, Mori M. Interaction between ESRα polymorphisms and environmental factors in osteoporosis. J Orthop Res. 2012;30(10):1529–34.CrossRefPubMed
26.
Zurück zum Zitat Wajanavisit W, Suppachokmongkorn S, Woratanarat P, Ongphiphadhanakul B, Tawonsawatruk T. The association of bone mineral density and G2014A polymorphism in the estrogen receptor alpha gene in osteoporotic hip fracture in Thai population. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2015;98(Suppl 8):S82–7.PubMed Wajanavisit W, Suppachokmongkorn S, Woratanarat P, Ongphiphadhanakul B, Tawonsawatruk T. The association of bone mineral density and G2014A polymorphism in the estrogen receptor alpha gene in osteoporotic hip fracture in Thai population. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2015;98(Suppl 8):S82–7.PubMed
27.
Zurück zum Zitat Gomez R, Magana JJ, Cisneros B, Perez-Salazar E, Faugeron S, Veliz D, Castro C, Rubio J, Casas L, Valdes-Flores M. Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population. Clin Genet. 2007;72(6):574–81.CrossRefPubMed Gomez R, Magana JJ, Cisneros B, Perez-Salazar E, Faugeron S, Veliz D, Castro C, Rubio J, Casas L, Valdes-Flores M. Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population. Clin Genet. 2007;72(6):574–81.CrossRefPubMed
28.
Zurück zum Zitat Ongphiphadhanakul B, Chanprasertyothin S, Payattikul P, Saetung S, Rajatanavin R. The implication of assessing a polymorphism in estrogen receptor alpha gene in the risk assessment of osteoporosis using a screening tool for osteoporosis in Asians. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2003;14(10):863–7.CrossRef Ongphiphadhanakul B, Chanprasertyothin S, Payattikul P, Saetung S, Rajatanavin R. The implication of assessing a polymorphism in estrogen receptor alpha gene in the risk assessment of osteoporosis using a screening tool for osteoporosis in Asians. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2003;14(10):863–7.CrossRef
29.
Zurück zum Zitat Ongphiphadhanakul B, Chanprasertyothin S, Payattikul P, Saetung S, Piaseu N, Chailurkit L, Rajatanavin R. Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2001;12(12):1015–9.CrossRef Ongphiphadhanakul B, Chanprasertyothin S, Payattikul P, Saetung S, Piaseu N, Chailurkit L, Rajatanavin R. Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2001;12(12):1015–9.CrossRef
30.
Zurück zum Zitat Shoukry A, Shalaby SM, Etewa RL, Ahmed HS, Abdelrahman HM. Association of estrogen receptor beta and estrogen-related receptor alpha gene polymorphisms with bone mineral density in postmenopausal women. Mol Cell Biochem. 2015;405(1–2):23–31.CrossRefPubMed Shoukry A, Shalaby SM, Etewa RL, Ahmed HS, Abdelrahman HM. Association of estrogen receptor beta and estrogen-related receptor alpha gene polymorphisms with bone mineral density in postmenopausal women. Mol Cell Biochem. 2015;405(1–2):23–31.CrossRefPubMed
31.
Zurück zum Zitat Huang HL, Tan HH, Chen BP, Li H, Xie JS, Zhao QZ. Correlation of polymorphism of estrogen receptor-β and camellia oil with post-menopausal osteoporosis in Zhuang women of Guangxi. Chinese Journal of Anatomy. 2015;03:323–325,343. Huang HL, Tan HH, Chen BP, Li H, Xie JS, Zhao QZ. Correlation of polymorphism of estrogen receptor-β and camellia oil with post-menopausal osteoporosis in Zhuang women of Guangxi. Chinese Journal of Anatomy. 2015;03:323–325,343.
32.
Zurück zum Zitat Moron FJ, Mendoza N, Vazquez F, Molero E, Quereda F, Salinas A, Fontes J, Martinez-Astorquiza T, Sanchez-Borrego R, Ruiz A. Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone. 2006;39(1):213–21.CrossRefPubMed Moron FJ, Mendoza N, Vazquez F, Molero E, Quereda F, Salinas A, Fontes J, Martinez-Astorquiza T, Sanchez-Borrego R, Ruiz A. Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone. 2006;39(1):213–21.CrossRefPubMed
33.
Zurück zum Zitat Albagha OM, FE MG, Reid DM, Ralston SH. Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2001;16(1):128–34.CrossRef Albagha OM, FE MG, Reid DM, Ralston SH. Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2001;16(1):128–34.CrossRef
34.
Zurück zum Zitat Kurt O, Yilmaz-Aydogan H, Uyar M, Isbir T, Seyhan MF, Can A. Evaluation of ERalpha and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women. Mol Biol Rep. 2012;39(6):6723–30.CrossRefPubMed Kurt O, Yilmaz-Aydogan H, Uyar M, Isbir T, Seyhan MF, Can A. Evaluation of ERalpha and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women. Mol Biol Rep. 2012;39(6):6723–30.CrossRefPubMed
35.
Zurück zum Zitat Kurabayashi T, Tomita M, Matsushita H, Yahata T, Honda A, Takakuwa K, Tanaka K. Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstet Gynecol. 1999;180(5):1115–20.CrossRefPubMed Kurabayashi T, Tomita M, Matsushita H, Yahata T, Honda A, Takakuwa K, Tanaka K. Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstet Gynecol. 1999;180(5):1115–20.CrossRefPubMed
36.
Zurück zum Zitat Ge JR, Zhu XX, Chen K. Effect of estrogen receptor gene Px haplotype on bone mineral density in female postmenopausal osteoporosis. Chin J Geriatr. 2006;25(6):416–9. Ge JR, Zhu XX, Chen K. Effect of estrogen receptor gene Px haplotype on bone mineral density in female postmenopausal osteoporosis. Chin J Geriatr. 2006;25(6):416–9.
37.
Zurück zum Zitat Ge JR, Wang HM, Zhu XX, Chen K. Effect of PvuIIpolymorphisms of estrogen receptor gene on filtering risk factors in postmenopansal osteoporosis. Chin J Osteoporos. 2006;12(1):38–40. Ge JR, Wang HM, Zhu XX, Chen K. Effect of PvuIIpolymorphisms of estrogen receptor gene on filtering risk factors in postmenopansal osteoporosis. Chin J Osteoporos. 2006;12(1):38–40.
38.
Zurück zum Zitat An SJ, Li E, Tong XX, Liu K, Zhao JS. Study on relationship between estrogen receptor gene polymorphism and syndrome differentiation typing of female postmenopausal osteoporosis in traditional Chinese medicine. Chinese Journal of Integrated Traditional and Western Medicine. 2000;20(12):907–10.PubMed An SJ, Li E, Tong XX, Liu K, Zhao JS. Study on relationship between estrogen receptor gene polymorphism and syndrome differentiation typing of female postmenopausal osteoporosis in traditional Chinese medicine. Chinese Journal of Integrated Traditional and Western Medicine. 2000;20(12):907–10.PubMed
39.
Zurück zum Zitat Wang KJ, Shi DQ, Sun LS, Jiang X, Lu YY, Dai J, Chen DY, Xu ZH, Jiang Q. Association of estrogen receptor alpha gene polymorphisms with bone mineral density: a meta-analysis. Chin Med J. 2012;125(14):2589–97.PubMed Wang KJ, Shi DQ, Sun LS, Jiang X, Lu YY, Dai J, Chen DY, Xu ZH, Jiang Q. Association of estrogen receptor alpha gene polymorphisms with bone mineral density: a meta-analysis. Chin Med J. 2012;125(14):2589–97.PubMed
40.
Zurück zum Zitat Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM. Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2007;18(3):295–305.CrossRef Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM. Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2007;18(3):295–305.CrossRef
41.
Zurück zum Zitat Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Gennari L, Albagha O, Ralston SH, Tsatsoulis A. Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: a meta-analysis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002;17(11):2048–60.CrossRef Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Gennari L, Albagha O, Ralston SH, Tsatsoulis A. Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: a meta-analysis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002;17(11):2048–60.CrossRef
Metadaten
Titel
Associations between ERα/β gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis
verfasst von
Heping Zhu
Jiannong Jiang
Qiang Wang
Jun Zong
Liang Zhang
Tieliang Ma
Youjia Xu
Leiyan Zhang
Publikationsdatum
01.12.2018
Verlag
BioMed Central
Erschienen in
BMC Endocrine Disorders / Ausgabe 1/2018
Elektronische ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0230-x

Weitere Artikel der Ausgabe 1/2018

BMC Endocrine Disorders 1/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.