Peter et al., APOE and Bone: a Meta-analysis

Figure S1: Quorum Flow chart of Literature Review

Supplemental Material: Search Strategy for APOE and BMD or Fractures

Population: All

Exposure: APOE

Comparator: APOE non-variant = un-exposed group

Outcome: BMD and fracture

Design: Association study

EXPOSURE/COMPARATOR
(APOE OR APOE$ OR Apolipoprotein E OR Apolipoprotein E2 OR Apolipoprotein E3 OR Apolipoprotein E4 OR Apolipoproteins E[MH] OR epsilon2 OR epsilon3 OR epsilon4 OR "e2"[Text Word] OR "e3"[Text Word] OR "e4"[Text Word] OR Apolipoprotein E genotype)
OUTCOME:
(fracture$ OR fracture$ OR Fractures, Bone[MH] OR

BMD OR bone mineral density OR BMC OR Bone mineral content OR bone density[MH] OR

DXA OR dual-energy X-ray absorptiometry OR X-ray absorptiometry OR “Absorptiometry, Photon"[MH] OR Osteo$ OR "Osteoporosis"[Mesh] OR "Osteoporosis, Postmenopausal"[Mesh])

Crossing

(APOE OR APOE$ OR Apolipoprotein E OR Apolipoprotein E2 OR Apolipoprotein E3 OR Apolipoprotein E4 OR Apolipoproteins E[MH] OR epsilon2 OR epsilon3 OR epsilon4 OR "e2"[Text Word] OR "e3"[Text Word] OR "e4"[Text Word] OR Apolipoprotein E genotype) AND (fracture$ OR fracture$ OR Fractures, Bone[MH] OR BMD OR bone mineral density OR BMC OR Bone mineral content OR bone density[MH] OR DXA OR dual-energy X ray absorptiometry OR X-ray absorptiometry OR “Absorptiometry, Photon"[MH] OR Osteo$ OR "Osteoporosis"[Mesh] OR "Osteoporosis, Postmenopausal"[Mesh])

 581 articles on April 3, 2008

 713 articles on May 27, 2008

Check if meta-analysis exists on APOE and BMD

(APOE OR APOE$ OR Apolipoprotein E OR Apolipoprotein E2 OR Apolipoprotein E3 OR Apolipoprotein E4 OR Apolipoproteins E[MH] OR epsilon2 OR epsilon3 OR epsilon4 OR "e2"[Text Word] OR "e3"[Text Word] OR "e4"[Text Word] OR Apolipoprotein E genotype OR genotype[MH]) AND (fracture$ OR fracture$ OR Fractures, Bone[MH] OR BMD OR bone mineral density OR BMC OR Bone mineral content OR bone density[MH] OR DXA OR dual-energy X ray absorptiometry OR X-ray absorptiometry OR “Absorptiometry, Photon"[MH] OR Osteo$ OR "Osteoporosis"[Mesh] OR "Osteoporosis, Postmenopausal"[Mesh]) ANDmeta-analysis

 14 articles on April 25, 2008

 But none of them looked at APOE and BMD

Download to EndNote

 713 articles were downloaded to the EndNote

Download to Word documents

 Articles were downloaded to word documents for abstract screening

 Exposure and outcomes were colored

 Exposure Blue

APOE, Apolipoprotein E, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Apolipoproteins E, epsilon2, epsilon3, epsilon4, e2, e3, e4, Apolipoprotein E genotype

 Outcomes: Red

BMD, Bone mineral density, BMC, Bone mineral content, bone density, Osteo, Osteoporosis, fracture, DXA, dual-energy X ray absorptiometry, X-ray absorptiometry

Retrieve Manuscript

 51 articles were retrieved

Peter et al., APOE and Bone: a Meta-analysis

Supplemental Table S1: Sensitivity Analysis for BMD phenotypes

Site / Sex / Studies included / Strata (Subjects) / Random effects / Fixed effects
Weighted mean difference / P-value / Heterogeneity, I2 P-value (%) / Weighted mean difference / P-value
FN / Both / All available / 15 (13986) / -0.002 (-0.007, 0.003) / 0.47 / 0.41 (4) / -0.002 (-0.007, 0.003) / 0.48
FN / Both / Caucasian / 15 (13986) / -0.002 (-0.007, 0.003) / 0.47 / 0.41 (4) / -0.002 (-0.007, 0.003) / 0.48
FN / Both / Excluding 1st / 14 (12468) / -0.003 (-0.009, 0.002) / 0.23 / 0.54 (0) / -0.003 (-0.009, 0.002) / 0.23
FN / Both / Excluding FOS & VitK / 11 (12105) / -0.002 (-0.009, 0.004) / 0.47 / 0.24 (21) / -0.002 (-0.007, 0.004) / 0.52
FN / Both / Excluding HWE deviating studies / 13 (12076) / -0.003 (-0.008, 0.003) / 0.32 / 0.50 (0) / -0.003 (-0.008, 0.003) / 0.32
FN / Both / Excluding most extreme study [1] / 14 (13724) / -0.001 (-0.006, 0.004) / 0.75 / 0.66 (0) / -0.001 (-0.006, 0.004) / 0.75
FN / F / All available / 11 (10658) / -0.003 (-0.009, 0.004) / 0.40 / 0.20 (26) / -0.002 (-0.007, 0.003) / 0.45
FN / F / Excluding FOS & VitK / 9 (9619) / -0.003 (-0.010, 0.005) / 0.50 / 0.14 (35) / -0.002 (-0.007, 0.004) / 0.56
FN / F / Excluding FOS & VitK, and 1st study / 8 (8101) / -0.004 (-0.012, 0.003) / 0.25 / 0.21 (28) / -0.003 (-0.009, 0.002) / 0.26
FN / M / All available / 4 (3328) / 0.001 (-0.018, 0.020) / 0.92 / 0.82 (0) / 0.001 (-0.018, 0.020) / 0.92
FN / M / Excluding FOS & VitK / 2 (2486) / -0.006 (-0.034, 0.023) / 0.70 / 0.57 (0) / -0.006 (-0.034, 0.023) / 0.70
FN / M / Excluding FOS & VitK, and 1st study / 1 (2220) / -0.010 (-0.041, 0.022) / 0.55 / NA / -0.010 (-0.041, 0.022) / 0.55
LS / Both / All available / 18 (10999) / -0.014 (-0.025, -0.003)* / 0.01 / <0.01 (51) / -0.009 (-0.016, -0.003)* / 0.007
LS / Both / Asian / 2 (394) / -0.082 (-0.129, -0.036)* / 0.0006 / 0.18 (44) / -0.080 (-0.114, -0.045)* / 5.1E-06
LS / Both / Caucasian / 15 (10493) / -0.006 (-0.012, 0.001) / 0.10 / 0.51 (0) / -0.006 (-0.012, 0.001) / 0.10
LS / Both / Excluding 1st / 17 (10715) / -0.011 (-0.022, -0.000)* / 0.04 / 0.02 (45) / -0.008 (-0.015, -0.001)* / 0.02
LS / Both / Excluding FOS & VitK / 14 (9109) / -0.014 (-0.027, -0.001)* / 0.04 / <0.01 (61) / -0.008 (-0.015, -0.001)* / 0.02
LS / Both / Excluding HWE deviating studies / 17 (10607) / -0.015 (-0.027, -0.003)* / 0.017 / <0.01 (54) / -0.009 (-0.016, -0.002)* / 0.009
LS / Both / Excluding most extreme study [2] / 17 (10889) / -0.009 (-0.018, -0.000)* / 0.04 / 0.13 (29) / -0.008 (-0.014, -0.001)* / 0.02
LS / Both / Mixed / 1 (112) / -0.057 (-0.114, -0.000)* / 0.049 / NA / -0.057 (-0.114, -0.000)* / 0.049
LS / F / All available / 14 (8862) / -0.019 (-0.032, -0.005)* / 0.006 / <0.01 (55) / -0.013 (-0.020, -0.005)* / 0.0008
LS / F / Excluding FOS & VitK / 12 (7816) / -0.019 (-0.034, -0.004)* / 0.01 / <0.01 (61) / -0.012 (-0.020, -0.004)* / 0.002
LS / F / Excluding FOS & VitK, and 1st study / 11 (7532) / -0.015 (-0.029, -0.000)* / 0.04 / 0.01 (56) / -0.010 (-0.018, -0.002)* / 0.01
LS / M / All available / 4 (2137) / 0.004 (-0.010, 0.018) / 0.58 / 0.58 (0) / 0.004 (-0.010, 0.018) / 0.58
LS / M / Excluding FOS & VitK / 2 (1293) / 0.008 (-0.008, 0.023) / 0.35 / 0.88 (0) / 0.008 (-0.008, 0.023) / 0.35
LS / M / Excluding FOS & VitK, and 1st study / 1 (697) / 0.007 (-0.010, 0.024) / 0.43 / NA / 0.007 (-0.010, 0.024) / 0.43
Total Body / Both / All available / 6 (2642) / -0.006 (-0.019, 0.008) / 0.41 / 0.16 (36) / -0.004 (-0.014, 0.006) / 0.48
Total Body / Both / Asian / 1 (284) / -0.038 (-0.066, -0.010)* / 0.007 / NA / -0.038 (-0.066, -0.010)* / 0.007
Total Body / Both / Caucasian / 5 (2358) / 0.002 (-0.009, 0.012) / 0.78 / 0.90 (0) / 0.002 (-0.009, 0.012) / 0.78
Total Body / Both / Excluding 1st / 5 (2358) / 0.002 (-0.009, 0.012) / 0.78 / 0.90 (0) / 0.002 (-0.009, 0.012) / 0.78
Total Body / Both / Excluding FOS & VitK / 2 (753) / -0.015 (-0.057, 0.027) / 0.48 / <0.01 (85) / -0.006 (-0.020, 0.008) / 0.42
Total Body / Both / Excluding HWE deviating studies / 6 (2642) / -0.006 (-0.019, 0.008) / 0.41 / 0.16 (36) / -0.004 (-0.014, 0.006) / 0.48
Total Body / Both / Excluding most extreme study [3] / 5 (2358) / 0.002 (-0.009, 0.012) / 0.78 / 0.90 (0) / 0.002 (-0.009, 0.012) / 0.78
Total Body / F / All available / 4 (1798) / -0.005 (-0.024, 0.013) / 0.57 / 0.06 (60) / -0.003 (-0.014, 0.009) / 0.64
Total Body / F / Excluding FOS & VitK / 2 (753) / -0.015 (-0.057, 0.027) / 0.48 / <0.01 (85) / -0.006 (-0.020, 0.008) / 0.42
Total Body / F / Excluding FOS & VitK, and 1st study / 1 (469) / 0.005 (-0.011, 0.021) / 0.55 / NA / 0.005 (-0.011, 0.021) / 0.55
Total Body / M / All available / 2 (844) / -0.009 (-0.033, 0.016) / 0.49 / 0.64 (0) / -0.009 (-0.033, 0.016) / 0.49
Total Hip / Both / All available / 8 (4622) / -0.001 (-0.012, 0.010) / 0.81 / 0.15 (35) / -0.002 (-0.010, 0.007) / 0.71
Total Hip / Both / Caucasian / 8 (4622) / -0.001 (-0.012, 0.010) / 0.81 / 0.15 (35) / -0.002 (-0.010, 0.007) / 0.71
Total Hip / Both / Excluding 1st / 7 (3104) / -0.006 (-0.016, 0.004) / 0.26 / 0.36 (10) / -0.006 (-0.016, 0.003) / 0.20
Total Hip / Both / Excluding FOS & VitK / 8 (4622) / -0.001 (-0.012, 0.010) / 0.81 / 0.15 (35) / -0.002 (-0.010, 0.007) / 0.71
Total Hip / Both / Excluding HWE deviating studies / 6 (2712) / -0.004 (-0.016, 0.009) / 0.55 / 0.28 (20) / -0.005 (-0.015, 0.006) / 0.37
Total Hip / Both / Excluding most extreme study [1] / 7 (4360) / 0.000 (-0.011, 0.011) / 0.97 / 0.17 (34) / -0.001 (-0.009, 0.008) / 0.91
Total Hip / F / All available / 7 (4026) / -0.001 (-0.014, 0.012) / 0.83 / 0.10 (44) / -0.002 (-0.011, 0.007) / 0.70
Total Hip / F / Excluding FOS & VitK / 7 (4026) / -0.001 (-0.014, 0.012) / 0.83 / 0.10 (44) / -0.002 (-0.011, 0.007) / 0.70
Total Hip / F / Excluding FOS & VitK, and 1st study / 6 (2508) / -0.006 (-0.019, 0.006) / 0.32 / 0.27 (22) / -0.007 (-0.018, 0.003) / 0.17
Total Hip / M / All available / 1 (596) / -0.001 (-0.026, 0.025) / 0.97 / NA / -0.001 (-0.026, 0.025) / 0.97
Total Hip / M / Excluding FOS & VitK / 1 (596) / -0.001 (-0.026, 0.025) / 0.97 / NA / -0.001 (-0.026, 0.025) / 0.97
Trochanter / Both / All available / 9 (3902) / -0.018 (-0.027, -0.008)* / 0.0002 / 0.67 (0) / -0.018 (-0.027, -0.008)* / 0.0002
Trochanter / Both / Asian / 1 (110) / -0.050 (-0.101, 0.001) / 0.05 / NA / -0.050 (-0.101, 0.001) / 0.05
Trochanter / Both / Caucasian / 8 (3792) / -0.017 (-0.026, -0.007)* / 0.0007 / 0.75 (0) / -0.017 (-0.026, -0.007)* / 0.0007
Trochanter / Both / Excluding 1st / 8 (3636) / -0.018 (-0.028, -0.009)* / 0.0002 / 0.62 (0) / -0.018 (-0.028, -0.009)* / 0.0002
Trochanter / Both / Excluding FOS & VitK / 5 (2021) / -0.022 (-0.034, -0.010)* / 0.0004 / 0.67 (0) / -0.022 (-0.034, -0.010)* / 0.0004
Trochanter / Both / Excluding HWE deviating studies / 9 (3902) / -0.018 (-0.027, -0.008)* / 0.0002 / 0.67 (0) / -0.018 (-0.027, -0.008)* / 0.0002
Trochanter / Both / Excluding most extreme study [2] / 8 (3792) / -0.017 (-0.026, -0.007)* / 0.0007 / 0.75 (0) / -0.017 (-0.026, -0.007)* / 0.0007
Trochanter / F / All available / 6 (2794) / -0.019 (-0.029, -0.008)* / 0.0004 / 0.41 (1) / -0.019 (-0.029, -0.008)* / 0.0004
Trochanter / F / Excluding FOS & VitK / 4 (1755) / -0.023 (-0.035, -0.010)* / 0.0003 / 0.63 (0) / -0.023 (-0.035, -0.010)* / 0.0003
Trochanter / F / Excluding FOS & VitK, and 1st study / 3 (1312) / -0.023 (-0.036, -0.011)* / 0.0003 / 0.45 (0) / -0.023 (-0.036, -0.011)* / 0.0003
Trochanter / M / All available / 3 (1108) / -0.013 (-0.035, 0.010) / 0.27 / 0.76 (0) / -0.013 (-0.035, 0.010) / 0.27
Trochanter / M / Excluding FOS & VitK / 1 (266) / 0.007 (-0.063, 0.077) / 0.84 / NA / 0.007 (-0.063, 0.077) / 0.84

FN, femoral neck; LS, lumbar spine; Both, sex-pooled analysis; F, female; M, male; FOS, Framingham Offspring Study, VitK, Vitamin K Clinical Trial

Supplemental Table S2: Meta-Regression Results for BMD Phenotypes

Site / Weighted Difference / P-Value
Mean / LOW / HIGH
FN / -0.004 / -0.011 / 0.003 / 0.306
LS / -0.012 / -0.025 / 0.000 / 0.055
Total hip / -0.002 / -0.013 / 0.010 / 0.763
Trochanter / -0.013 / -0.023 / -0.003 / 0.011

FN, femoral neck; LS, lumbar spine.

Supplemental Table S3: Sensitivity Analysis for Fractures

Site / Sex / Incident / Studies excluded / Studies (Subjects) / OR (95% CI)
Random effects / Heterogeneity, I2
P-value (%) / OR (95% CI)
Fixed effects
All / Both / Both / 6 (3759) / 0.92 (0.71, 1.18) / 0.69 (0) / 0.92 (0.71, 1.18)
All / Both / Incident / 3 (2738) / 1.04 (0.76, 1.42) / 0.89 (0) / 1.04 (0.76, 1.42)
All / Both / Prevalent / 4 (2352) / 0.80 (0.63, 1.02) / 0.70 (0) / 0.80 (0.63, 1.02)
All / F / Both / 4 (2477) / 0.97 (0.72, 1.30) / 0.60 (0) / 0.97 (0.72, 1.30)
All / F / Incident / 2 (2052) / 1.06 (0.75, 1.51) / 0.71 (0) / 1.06 (0.75, 1.51)
All / F / Prevalent / 3 (1756) / 0.83 (0.64, 1.07) / 0.62 (0) / 0.83 (0.64, 1.07)
All / M / Both / 2 (1282) / 0.78 (0.47, 1.28) / 0.44 (0) / 0.78 (0.47, 1.28)
All / M / Incident / 1 (686) / 0.94 (0.46, 1.92) / NA / 0.94 (0.46, 1.92)
All / M / Prevalent / 1 (596) / 0.64 (0.31, 1.30) / NA / 0.64 (0.31, 1.30)
Hip / Both / Both / 7 (10189) / 1.12 (0.77, 1.65) / 0.14 (40) / 1.15 (0.89, 1.48)
Hip / Both / Both / 1st / 7 (10189) / 1.12 (0.77, 1.65) / 0.14 (40) / 1.15 (0.89, 1.48)
Hip / Both / Incident / 1st / 5 (7263) / 1.05 (0.78, 1.40) / 0.74 (0) / 1.05 (0.78, 1.40)
Hip / Both / Incident / 6 (9013) / 1.22 (0.88, 1.69) / 0.26 (24) / 1.19 (0.92, 1.55)
Hip / Both / Prevalent / 1 (1176) / 0.31 (0.07, 1.38) / NA / 0.31 (0.07, 1.38)
Hip / F / Both / 4 (6943) / 1.02 (0.56, 1.87) / 0.05 (62) / 1.12 (0.84, 1.50)
Hip / F / Incident / 3 (5767) / 1.21 (0.69, 2.13) / 0.08 (60) / 1.18 (0.88, 1.59)
Hip / F / Prevalent / 1 (1176) / 0.31 (0.07, 1.38) / NA / 0.31 (0.07, 1.38)
Hip / M / Both / 2 (3246) / 1.25 (0.73, 2.15) / 0.63 (0) / 1.25 (0.73, 2.15)
Hip / M / Incident / 2 (3246) / 1.25 (0.73, 2.15) / 0.63 (0) / 1.25 (0.73, 2.15)
Non-vertebral / Both / Both / 2 (5866) / 1.08 (0.87, 1.36) / 0.23 (31) / 1.07 (0.90, 1.27)
Non-vertebral / Both / Incident / 2 (5866) / 1.08 (0.87, 1.36) / 0.23 (31) / 1.07 (0.90, 1.27)
Non-vertebral / F / Both / 1 (3306) / 1.00 (0.81, 1.22) / NA / 1.00 (0.81, 1.22)
Non-vertebral / F / Incident / 1 (3306) / 1.00 (0.81, 1.22) / NA / 1.00 (0.81, 1.22)
Non-vertebral / M / Both / 1 (2560) / 1.27 (0.91, 1.78) / NA / 1.27 (0.91, 1.78)
Non-vertebral / M / Incident / 1 (2560) / 1.27 (0.91, 1.78) / NA / 1.27 (0.91, 1.78)
Other / Both / Both / 1 (1625) / 0.83 (0.56, 1.23) / NA / 0.83 (0.56, 1.23)
Other / Both / Both / 1st / 1 (1625) / 0.83 (0.56, 1.23) / NA / 0.83 (0.56, 1.23)
Other / Both / Incident / 1 (1625) / 0.83 (0.56, 1.23) / NA / 0.83 (0.56, 1.23)
Other / F / Both / 1 (1625) / 0.83 (0.56, 1.23) / NA / 0.83 (0.56, 1.23)
Other / F / Incident / 1 (1625) / 0.83 (0.56, 1.23) / NA / 0.83 (0.56, 1.23)
Vertebral / Both / Both / 6 (6886) / 1.03 (0.75, 1.43) / 0.04 (57) / 1.09 (0.90, 1.33)
Vertebral / Both / Both / 1st / 6 (6886) / 1.03 (0.75, 1.43) / 0.04 (57) / 1.09 (0.90, 1.33)
Vertebral / Both / Incident / 1st / 2 (2900) / 0.81 (0.55, 1.20) / 0.46 (0) / 0.81 (0.55, 1.20)
Vertebral / Both / Incident / 3 (4304) / 0.93 (0.65, 1.34) / 0.32 (13) / 0.93 (0.67, 1.30)
Vertebral / Both / Prevalent / 5 (2582) / 1.03 (0.74, 1.42) / 0.04 (60) / 1.08 (0.88, 1.31)
Vertebral / F / Both / 4 (4819) / 1.24 (0.95, 1.61) / 0.25 (26) / 1.23 (0.99, 1.53)
Vertebral / F / Incident / 2 (2923) / 1.03 (0.69, 1.52) / 0.29 (9) / 1.02 (0.70, 1.48)
Vertebral / F / Prevalent / 3 (1896) / 1.25 (0.92, 1.69) / 0.20 (38) / 1.24 (0.99, 1.56)
Vertebral / M / Both / 2 (2067) / 0.58 (0.35, 0.96)* / 0.73 (0) / 0.58 (0.35, 0.96)*
Vertebral / M / Incident / 1 (1381) / 0.64 (0.30, 1.35) / NA / 0.64 (0.30, 1.35)
Vertebral / M / Prevalent / 2 (686) / 0.71 (0.48, 1.07) / 0.30 (6) / 0.72 (0.49, 1.06)
Wrist / Both / Both / 3 (7298) / 1.14 (0.80, 1.63) / 0.29 (19) / 1.11 (0.82, 1.49)
Wrist / Both / Both / 1st / 3 (7298) / 1.14 (0.80, 1.63) / 0.29 (19) / 1.11 (0.82, 1.49)
Wrist / Both / Incident / 1st / 2 (5657) / 0.98 (0.70, 1.37) / 0.89 (0) / 0.98 (0.70, 1.37)
Wrist / Both / Incident / 3 (7298) / 1.14 (0.80, 1.63) / 0.29 (19) / 1.11 (0.82, 1.49)
Wrist / F / Both / 2 (4938) / 1.22 (0.70, 2.14) / 0.12 (59) / 1.12 (0.82, 1.53)
Wrist / F / Incident / 2 (4938) / 1.22 (0.70, 2.14) / 0.12 (59) / 1.12 (0.82, 1.53)
Wrist / M / Both / 1 (2360) / 1.04 (0.42, 2.56) / NA / 1.04 (0.42, 2.56)
Wrist / M / Incident / 1 (2360) / 1.04 (0.42, 2.56) / NA / 1.04 (0.42, 2.56)

*, significant at P<0.05; NA, not applicable. Both, sex-pooled analysis; F, female; M, male;

References

1.Pluijm, S.M., Dik, M.G., Jonker, C., Deeg, D.J., van Kamp, G.J., Lips, P. (2002) Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people. Osteoporos Int13, 701-9.

2.Lee, S.I., Lee, S.Y., Yoo, W.H. (2005) Association of apolipoprotein E polymorphism with bone mineral density in postmenopausal women with rheumatoid arthritis. Rheumatology (Oxford)44, 1067-8.

3.Shiraki, M., Shiraki, Y., Aoki, C., Hosoi, T., Inoue, S., Kaneki, M., Ouchi, Y. (1997) Association of bone mineral density with apolipoprotein E phenotype. J Bone Miner Res12, 1438-45.