Table 2.
Associations with fractures and total hip bone mineral densitya
| Gene/polymorphism | Hip fracture HR (95% CI) | Nonvertebral, nonhip fracture HR (95% CI) | Vertebral fracture OR (95% CI) | Total hip BMD (g/cm2) Mean (95% CI) | |
|---|---|---|---|---|---|
| Total no. | 6575 | 6068 | 2475 | 6515 | |
| No. of fractures | 849 | 2496 | 658 | ||
| ALOX15_G48924T | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| GT | 1.03 (0.9–1.19) | 1.02 (0.93–1.11) | 1.01 (0.83–1.24) | 0.76 (0.76–0.77) | |
| TT | 1.33 (1.00–1.77) | 1.02 (0.84–1.23) | 0.78 (0.49–1.25) | 0.75 (0.74–0.77) | |
| ALOX15_G49010C | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| GC | 1.06 (0.92–1.23) | 1.00 (0.92–1.09) | 0.91 (0.75–1.12) | 0.76 (0.76–0.77) | |
| CC | 1.25 (0.93–1.68) | 0.98 (0.81–1.19) | 0.72 (0.44–1.17) | 0.75 (0.74–0.77) | |
| ALOX15_C51425T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| CT | 1.06 (0.92–1.22) | 0.94 (0.86–1.02) | 0.92 (0.75–1.13) | 0.76 (0.76–0.76) | |
| TT | 0.92 (0.70–1.19) | 1.00 (0.86–1.16) | 0.98 (0.69–1.39) | 0.76 (0.75–0.77) | |
| ALOX15_A57901G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| AG | 1.10 (0.93–1.29) | 1.01 (0.91–1.11) | 0.93 (0.73–1.17) | 0.76 (0.76–0.77) | |
| GG | 0.62 (0.29–1.31) | 0.93 (0.65–1.34) | 0.62 (0.23–1.66) | 0.76 (0.74–0.79) | |
| BMP2_C117863T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| CT | 0.84 (0.71–0.98) | 0.98 (0.89–1.08) | 1.05 (0.83–1.33) | 0.76 (0.75–0.76) | |
| TT | 0.78 (0.65–0.94) | 0.96 (0.86–1.08) | 0.91 (0.69–1.20) | 0.76 (0.75–0.77) | |
| BMP2_A125611G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.75 (0.74–0.76) |
| AG | 0.78 (0.60–1.00) | 0.93 (0.80–1.08) | 1.33 (0.90–1.97) | 0.76 (0.76–0.77) | |
| GG | 0.98 (0.77–1.26) | 0.96 (0.83–1.12) | 1.51 (1.03–2.23) | 0.76 (0.75–0.76) | |
| BMP2_G149529A | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| GA | 1.05 (0.84–1.31) | 1.01 (0.88–1.15) | 0.87 (0.63–1.19) | 0.76 (0.75–0.76) | |
| AA | 0.93 (0.74–1.17) | 0.99 (0.86–1.13) | 0.89 (0.65–1.23) | 0.76 (0.75–0.76) | |
| BMP2_C167584T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| CT | 0.94 (0.77–1.15) | 1.06 (0.94–1.19) | 1.03 (0.77–1.37) | 0.75 (0.75–0.76) | |
| TT | 0.63 (0.20–1.96) | 1.15 (0.68–1.95) | 2.13 (0.75–6.02) | 0.77 (0.73–0.82) | |
| CALCR_C1654T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| CT | 1.05 (0.78–1.42) | 1.01 (0.85–1.21) | 1.11 (0.73–1.68) | 0.76 (0.75–0.76) | |
| TT | 1.00 (0.75–1.33) | 1.00 (0.84–1.19) | 0.93 (0.62–1.40) | 0.76 (0.76–0.76) | |
| CASR_C3403G | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| CG | 0.85 (0.65–1.10) | 0.97 (0.83–1.12) | 1.12 (0.79–1.60) | 0.76 (0.75–0.77) | |
| GG | 0.31 (0.04–2.19) | 1.53 (0.87–2.70) | 1.38 (0.32–5.91) | 0.75 (0.7–0.8) | |
| COL1A1_G296T | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| GT | 0.91 (0.77–1.07) | 0.98 (0.89–1.07) | 1.07 (0.85–1.33) | 0.76 (0.75–0.76) | |
| TT | 0.98 (0.63–1.53) | 0.90 (0.67–1.21) | 1.56 (0.82–2.97) | 0.76 (0.74–0.78) | |
| COL1A1_G2046T | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| GT | 1.07 (0.93–1.24) | 1.05 (0.96–1.14) | 1.09 (0.89–1.34) | 0.76 (0.75–0.76) | |
| TT | 1.03 (0.71–1.51) | 1.15 (0.93–1.42) | 0.94 (0.56–1.58) | 0.76 (0.74–0.77) | |
| COMT_G1947A | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| GA | 1.26 (1.05–1.51) | 1.00 (0.9–1.11) | 1.18 (0.92–1.52) | 0.76 (0.75–0.76) | |
| AA | 1.17 (0.96–1.44) | 0.98 (0.87–1.10) | 1.09 (0.83–1.44) | 0.76 (0.75–0.77) | |
| CYP1A1_A6570G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| AG | 0.91 (0.68–1.22) | 1.02 (0.87–1.21) | 0.97 (0.65–1.44) | 0.75 (0.74–0.77) | |
| GG | 1.40 (0.58–3.38) | 0.76 (0.36–1.59) | 1.42 (0.26–7.92) | 0.79 (0.75–0.84) | |
| ESR1_T938C | TT | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| TC | 1.00 (0.85–1.17) | 1.01 (0.92–1.11) | 1.18 (0.94–1.48) | 0.76 (0.76–0.76) | |
| CC | 0.96 (0.79–1.17) | 0.93 (0.83–1.05) | 1.11 (0.84–1.46) | 0.76 (0.75–0.77) | |
| ESR1_A984G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| AG | 1.14 (0.99–1.32) | 0.93 (0.86–1.02) | 1.21 (0.99–1.48) | 0.76 (0.75–0.76) | |
| GG | 1.01 (0.80–1.26) | 0.91 (0.79–1.04) | 1.10 (0.80–1.51) | 0.76 (0.75–0.77) | |
| ESR1_C1335G | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| CG | 0.93 (0.81–1.08) | 1.00 (0.91–1.09) | 1.16 (0.95–1.42) | 0.76 (0.75–0.76) | |
| GG | 1.23 (0.91–1.64) | 1.06 (0.88–1.28) | 1.64 (1.07–2.50) | 0.77 (0.76–0.79) | |
| FRZB1_A–757G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| AG | 0.89 (0.66–1.20) | 0.92 (0.77–1.11) | 0.74 (0.5–1.09) | 0.76 (0.76–0.77) | |
| GG | 0.94 (0.71–1.26) | 1.01 (0.84–1.20) | 0.70 (0.48–1.03) | 0.76 (0.75–0.76) | |
| FRZB1_G19524A | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| GA | 0.96 (0.83–1.11) | 0.95 (0.87–1.03) | 1.13 (0.92–1.38) | 0.76 (0.76–0.77) | |
| AA | 1.01 (0.76–1.35) | 0.97 (0.82–1.16) | 1.44 (0.99–2.09) | 0.76 (0.75–0.77) | |
| FRZB1_C26794G | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| CG | 0.95 (0.78–1.15) | 0.96 (0.86–1.07) | 0.79 (0.60–1.04) | 0.76 (0.75–0.77) | |
| GG | 1.05 (0.44–2.54) | 0.98 (0.56–1.73) | 1.78 (0.48–6.52) | 0.74 (0.7–0.78) | |
| GSTP_A2627G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| AG | 0.92 (0.80–1.07) | 0.96 (0.88–1.04) | 0.96 (0.78–1.17) | 0.76 (0.76–0.76) | |
| GG | 0.89 (0.71–1.12) | 1.04 (0.91–1.19) | 1.05 (0.77–1.43) | 0.76 (0.75–0.77) | |
| LRP5_G1980A | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.76) |
| GA | 1.05 (0.86–1.28) | 1.07 (0.95–1.21) | 1.17 (0.87–1.56) | 0.76 (0.75–0.76) | |
| AA | 0.69 (0.22–2.14) | 0.98 (0.54–1.78) | 2.04 (0.53–7.96) | 0.76 (0.71–0.8) | |
| MMP1_135792 (–/G) | 1G/1G | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| 1G/2G | 0.94 (0.80–1.10) | 0.99 (0.9–1.09) | 1.02 (0.82–1.28) | 0.76 (0.76–0.77) | |
| 2G/2G | 1.03 (0.85–1.25) | 1.03 (0.92–1.15) | 1.25 (0.96–1.64) | 0.76 (0.75–0.76) | |
| MMP2_C595T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| CT | 0.98 (0.85–1.14) | 1.00 (0.92–1.09) | 0.79 (0.65–0.96) | 0.76 (0.76–0.77) | |
| TT | 1.20 (0.92–1.56) | 0.89 (0.74–1.07) | 0.44 (0.27–0.72) | 0.76 (0.75–0.78) | |
| MMP2_A1829G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.77) |
| AG | 0.92 (0.77–1.10) | 1.02 (0.92–1.14) | 1.21 (0.94–1.57) | 0.76 (0.75–0.76) | |
| GG | 0.93 (0.77–1.13) | 1.04 (0.93–1.17) | 1.24 (0.94–1.64) | 0.76 (0.75–0.76) | |
| MMP13_A326G | AA | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.77) |
| AG | 1.01 (0.87–1.17) | 1.05 (0.96–1.14) | 1.16 (0.95–1.41) | 0.76 (0.75–0.76) | |
| GG | 1.21 (0.97–1.50) | 1.07 (0.93–1.22) | 0.87 (0.62–1.22) | 0.75 (0.74–0.76) | |
| MTHFR_C677T | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.76–0.77) |
| CT | 0.96 (0.83–1.11) | 1.00 (0.92–1.09) | 0.97 (0.80–1.19) | 0.76 (0.75–0.76) | |
| TT | 1.09 (0.88–1.36) | 1.07 (0.94–1.22) | 0.94 (0.68–1.29) | 0.75 (0.75–0.76) | |
| PPARc_C34G | CC | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| CG | 0.80 (0.67–0.95) | 1.06 (0.97–1.17) | 0.82 (0.66–1.04) | 0.76 (0.76–0.77) | |
| GG | 1.21 (0.75–1.97) | 1.29 (0.97–1.73) | 0.92 (0.44–1.92) | 0.76 (0.73–0.78) | |
| PRL_T228C | TT | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.75 (0.74–0.77) |
| TC | 0.85 (0.63–1.15) | 0.81 (0.68–0.97) | 0.74 (0.48–1.15) | 0.76 (0.76–0.77) | |
| CC | 0.87 (0.65–1.16) | 0.80 (0.67–0.95) | 0.78 (0.51–1.19) | 0.76 (0.75–0.76) | |
| PRL_G1627T | GG | 1.00 (Ref.) | 1.00 (Ref.) | 1.00 (Ref.) | 0.76 (0.75–0.76) |
| GT | 0.89 (0.77–1.03) | 1.03 (0.94–1.13) | 0.84 (0.68–1.03) | 0.76 (0.76–0.76) | |
| TT | 0.99 (0.81–1.21) | 1.10 (0.97–1.24) | 1.10 (0.83–1.46) | 0.76 (0.75–0.76) |
BMD, bone mineral density; HR, hazard ratio; 95% CI, 98% confidence interval
a
All analyses adjusted for age, clinic site, and self-reported ethnicity (northern, central, and southern European) Bold values are statistically significant results