Background
Methods
Study cohorts
Dietary assessment
Examinations in the clinical sub-cohorts
Proteomics profiling and measurement of clinical biomarkers
Bone mineral density and body composition in sub-cohort 1
Exposure and covariates
Hip fractures
Statistical analysis
Cox regression models to investigate meat intake and risk for hip fracture
Linear regression models in the clinical sub-cohorts
Meat intake and protein and clinical biomarkers
Meat intake, bone mineral density, and body composition
Results
Background characteristics
Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 | |
---|---|---|---|---|---|
Mean intake of meat (frequency per day (SD)) | 0.45 (0.18) | 0.85 (0.12) | 1.14 (0.14) | 1.49 (0.17) | 2.47 (1.13) |
Gram per day (SD) | 44 (21) | 76 (24) | 95 (28) | 111 (34) | 165 (117) |
Number of participants | 16, 125 | 16, 389 | 17, 743 | 16, 325 | 17, 021 |
Sex | |||||
Female | 7357 (45.6) | 7059 (43.1) | 8310 (46.8) | 7786 (47.7) | 7664 (45.0) |
Male | 8768 (54.4) | 9330 (56.9) | 9433 (53.2) | 8539 (52.3) | 9357 (55.0) |
Age, mean years (SD) | 63.6 (9.7) | 61.4 (9.6) | 60.5 (9.4) | 60.9 (9.4) | 61.5 (9.5) |
Educational attainment | |||||
≤ 9 years | 6631 (41.3) | 6151 (37.6) | 6497 (36.7) | 6122 (37.6) | 6329 (37.3) |
10–12 years | 6693 (41.7) | 7262 (44.4) | 8021 (45.3) | 7285 (44.7) | 7804 (45.9) |
> 12 years | 2740 (17.1) | 2942 (18.0) | 3198 (18.1) | 2887 (17.7) | 2852 (16.8) |
Height, mean cm (SD) | 171 (8.8) | 172 (8.8) | 171 (8.8) | 171 (8.8) | 172 (9.0) |
BMI, mean kg/m2 (SD) | 25.3 (3.8) | 25.3 (3.6) | 25.5 (3.7) | 25.5 (3.7) | 25.7 (4.0) |
Any calcium supplement* | |||||
No | 12,998 (80.6) | 13,294 (81.1) | 14,387 (81.1) | 13,066 (80.0) | 13,659 (80.2) |
Yes | 3127 (19.4) | 3095 (18.9) | 3356 (18.9) | 3259 (20.0) | 3362 (19.8) |
Calcium supplement | |||||
No | 15,355 (95.2) | 15,758 (96.1) | 17,070 (96.2) | 15,674 (96.0) | 16,309 (95.8) |
Yes | 770 (4.8) | 631 (3.9) | 673 (3.8) | 651 (4.0) | 712 (4.2) |
Any vitamin D supplement* | |||||
No | 13, 009 (80.7) | 13, 306 (81.2) | 14, 350 (80.9) | 13, 048 (79.9) | 13, 646 (80.2) |
Yes | 3116 (19.3) | 3083 (18.8) | 3393 (19.1) | 3277 (20.1) | 3375 (19.8) |
Cortisone | |||||
No | 14, 518 (90.0) | 14, 848 (90.6) | 16, 012 (90.2) | 14, 674 (89.9) | 15, 187 (89.2) |
Yes | 1607 (10.0) | 1541 (9.4) | 1731 (9.8) | 1651 (10.1) | 1834 (10.8) |
Exercise | |||||
< 1 h/week | 2793 (19.9) | 3044 (20.8) | 3392 (21.3) | 3084 (20.9) | 3367 (22.0) |
1 h/week | 2761 (19.7) | 3122 (21.3) | 3527 (22.1) | 3284 (22.2) | 3073 (20.1) |
2–3 h/week | 4536 (32.4) | 4724 (32.2) | 5234 (32.8) | 4800 (32.5) | 4860 (31.7) |
4–5 h/week | 1834 (13.1) | 1841 (12.6) | 1904 (11.9) | 1749 (11.8) | 1893 (12.4) |
> 5 h/week | 2095 (14.9) | 1926 (13.1) | 1903 (11.9) | 1845 (12.5) | 2128 (13.9) |
Walking | |||||
Never/seldom | 1857 (12.9) | 1813 (12.1) | 1980 (12.1) | 1825 (12.2) | 2045 (13.0) |
< 20 min/day | 2962 (20.6) | 3277 (21.9) | 3685 (22.6) | 3328 (22.2) | 3392 (21.6) |
20–40 min/day | 4345 (30.2) | 4779 (32.0) | 5300 (32.5) | 4775 (31.8) | 4857 (31.0) |
40–60 min/day | 2446 (17.0) | 2512 (16.8) | 2708 (16.6) | 2610 (17.4) | 2533 (16.1) |
1–1.5 h/day | 1519 (10.6) | 1427 (9.5) | 1460 (9.0) | 1335 (8.9) | 1542 (9.8) |
> 1.5 h/day | 1268 (8.8) | 1142 (7.6) | 1172 (7.2) | 1122 (7.5) | 1324 (8.4) |
Smoking status | |||||
Current | 3924 (24.9) | 3763 (23.3) | 4157 (23.7) | 3941 (24.5) | 4056 (24.2) |
Former | 4807 (30.5) | 5257 (32.6) | 5640 (32.2) | 5043 (31.3) | 5316 (31.7) |
Never | 7029 (44.6) | 7115 (44.1) | 7713 (44.0) | 7129 (44.2) | 7409 (44.2) |
Charlson’s comorbidity index | |||||
0 | 12, 926 (80.2) | 13, 810 (84.3) | 14, 940 (84.2) | 13, 633 (83.5) | 13, 880 (81.5) |
1 | 1934 (12.0) | 1552 (9.5) | 1662 (9.4) | 1643 (10.1) | 1900 (11.2) |
≥ 2 | 1265 (7.8) | 1027 (6.3) | 1141 (6.4) | 1049 (6.4) | 1241 (7.3) |
Living alone | |||||
No | 10, 895 (72.4) | 12, 248 (79.5) | 13, 599 (82.0) | 12, 554 (82.3) | 13, 029 (81.7) |
Yes | 4158 (27.6) | 3160 (20.5) | 2991 (18.0) | 2707 (17.7) | 2912 (18.3) |
Mean daily intakes of residual-adjusted nutrients (SD) | |||||
Vitamin D (µg) | 5.5 (3.3) | 5.6 (2.6) | 5.6 (2.3) | 5.7 (2.4) | 6.0 (2.6) |
Retinol (g) | 0.86 (0.5) | 0.97 (0.6) | 1.0 (0.6) | 1.1 (0.7) | 1.4 (1.3) |
Phosphorous (mg) | 1826 (484) | 1805 (449) | 1752 (435) | 1726 (428) | 1714 (417) |
Protein (g) | 85.9 (21.6) | 88.3 (20.6) | 87.6 (20.3) | 87.5 (20.3) | 90 (21.2) |
Alcohol (g) | 6.0 (8.7) | 7.2 (8.4) | 7.6 (8.7) | 7.9 (9.0) | 8.7(11) |
Saturated fat (g) | 30 (16) | 33 (16) | 35(16) | 37 (17) | 43 (20) |
Calcium (mg) | 1404 (526) | 1335 (455) | 1263 (427) | 1216 (408) | 1145 (388) |
Energy (kcal) | 1878 (759) | 2124 (772) | 2212 (786) | 2317 (810) | 2656 (1050) |
Mean daily consumption of food groups (frequency per day) and SD | |||||
Meat | 0.45 (0.18) | 0.85 (0.12) | 1.14 (0.14) | 1.49 (0.17) | 2.47 (1.13) |
Chicken | 0.07 (0.05) | 0.08 (0.06) | 0.09 (0.07) | 0.10 (.08) | 0.14 (0.2) |
Cheese | 2.8 (2.3) | 2.9 (2.3) | 2.9 (2.2) | 2.9 (2.2) | 2.9 (2.2) |
Fermented milk | 0.8 (1.0) | 0.8 (1.0) | 0.8 (0.97) | 0.8 (1.0) | 0.8 (1.02) |
Milk | 1.2 (1.4) | 1.3 (1.4) | 1.3 (1.4) | 1.3 (1.4) | 1.4(1.4) |
Fish and shellfish | 0.4 (0.4) | 0.5 (0.4) | 0.5 (0.4) | 0.5 (0.4) | 0.7 (0.7) |
Fruits and vegetables | 3.9 (2.9) | 4.1 (2.4) | 4.3 (2.3) | 4.6 (2.5) | 5.2 (3.1) |
Time to hip fracture
Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 | Per serving | |
---|---|---|---|---|---|---|
Mean intake of meat (frequency per day (SD)) | 0.45 (0.18) | 0.85 (0.12) | 1.14 (0.14) | 1.49 (0.17) | 2.47 (1.13) | |
Overall | ||||||
Number of persons with hip fracture | 1228 | 1002 | 967 | 957 | 1122 | |
Person-years of follow-up | 255,420 | 265,547 | 282,598 | 266,193 | 268,237 | |
Crude rate/1000 person-years (95% CI) | 4.8 (4.5; 5.1) | 3.8 (3.5; 4.0) | 3.4 (3.2; 3.6) | 3.6 (3.4; 3.8) | 4.1 (3.9; 4.4) | |
Age-adjusted HR (95% CI) | 1.05 (0.97, 1.14) P = 0.23 | 1.00 (ref) | 1.00 (0.91, 1.08) | 1.01 (0.92, 1.10) | 1.08 (0.98, 1.18) | 1.02 (1.00; 1.05) P = 0.08 |
P = 0.25 | P = 0.81 | P = 0.09 | ||||
Multivariable-adjusted HR (95% CI)* | 1.00 (0.92, 1.08) P = 0.99 | 1.00 (ref) | 1.02 (0.94, 1.11) P = 0.64 | 1.05 (0.97, 1.15) P = 0.25 | 1.11 (1.01, 1.21) P = 0.03 | 1.03 (1.00; 1.06) P = 0.02 |
Women | ||||||
Number of persons with hip fracture | 719 | 593 | 587 | 601 | 687 | |
Person-years of follow-up | 116,789 | 117,588 | 132,518 | 125,873 | 121,958 | |
Crude rate/1000 person-years (95% CI) | 6.2 (5.7; 6.6) | 5.0 (4.7; 5.5) | 4.4 (4.1; 4.8) | 4.8 (4.4; 5.2) | 5.6 (5.2; 6.1) | |
Age-adjusted HR (95% CI) | 1.04 (0.94, 1.16) P = 0.41 | 1.00 (ref) | 1.00 (0.90, 1.12) | 1.04 (0.93, 1.16) | 1.10 (0.99, 1.23) | 1.03(1.00, 1.06) P = 0.09 |
P = 0.90 | P = 0.48 | P = 0.07 | ||||
Multivariable-adjusted HR (95% CI)* | 1.00 (0.90, 1.11) P = 0.97 | 1.00 (ref) | 1.03 (0.92, 1.15) P = 0.64 | 1.08 (0.97, 1.21) P = 0.18 | 1.13 (1.01, 1.26) P = 0.03 | 1.04 (1.00, 1.08) P = 0.03 |
Men | ||||||
Number of persons with hip fracture | 509 | 409 | 380 | 356 | 435 | |
Person-years of follow-up | 138,631 | 147,959 | 150,080 | 140,32 | 146,279 | |
Crude rate/1000 person-years (95% CI) | 3.6 (3.4; 4.0) | 2.8 (2.5; 3.0) | 2.5 (2.3; 2.8) | 2.5 (2.3; 2.8)) | 2.9 (2.7; 3.3) | |
Age-adjusted HR (95% CI) | 1.06 (0.93, 1.20) P = 0.38 | 1.00 (ref) | 0.98 (0.85, 1.12) | 0.96 (0.84, 1.10) | 1.04 (0.91, 1.19) | 1.02 (0.98, 1.06) P = 0.37 |
P = 0.71 | P = 0.59 | P = 0.57 | ||||
Multivariable-adjusted HR (95% CI)* | 0.99 (0.87, 1.13) P = 0.88 | 1.00 (ref) | 1.00 (0.88, 1.15) P = 0.94 | 1.00 (0.87, 1.15) P = 0.98 | 1.04 (0.90, 1.20) P = 0.56 | 1.02 (0.98, 1.06) P = 0.37 |
Meat intake, circulating proteins, and clinical biomarkers
Sub-cohort 1 Women, n = 4656 | Sub-cohort 2 Men and women, n = 6862 | Sub-cohort 2 Men, n = 4475 | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Crude | Adjusted | Crude | Adjusted | Crude | Adjusted | ||||||||||||||||||
β-coeff | p | β-coeff | p | β-coeff | p | β-coeff | p | β-coeff | p | β-coeff | p | ||||||||||||
BMP-6 | Bone morphogenetic protein 6 | − 0.01 | 0.27 | − 0.06 | 0.49 | 0.04 | 0.009 | 0.018 | 0.22 | 0.04 | 0.05 | 0.013 | 0.49 | ||||||||||
IL-6 | Interleukin-6 | 0.025 | 0.007 | 0.032 | 0.001 | 0.06 | < 0.001 | 0.06 | < 0.001 | 0.05 | 0.01 | 0.05 | 0.03 | ||||||||||
FGF-21 | Fibroblast growth factor 21 | 0.024 | 0.009 | 0.035 | < 0.001 | 0.06 | < 0.001 | 0.08 | < 0.001 | 0.06 | < 0.001 | 0.08 | < 0.001 | ||||||||||
DCN | Decorin | − 0.009 | 0.33 | − 0.008 | 0.40 | 0.04 | 0.003 | 0.02 | 0.18 | 0.05 | 0.002 | 0.03 | 0.06 | ||||||||||
hOSCAR | Osteoclast-associated immunoglobulin-like receptor | − 0.006 | 0.54 | − 0.015 | 0.13 | 0.03 | 0.04 | 0.014 | 0.37 | 0.05 | 0.009 | 0.03 | 0.11 | ||||||||||
LEP | Leptin | 0.044 | < 0.001 | 0.053 | < 0.001 | 0.06 | < 0.001 | 0.10 | 0.04 | 0.09 | < 0.001 | 0.12 | < 0.001 | ||||||||||
OPG | Osteoprotegerin | − 0.009 | 0.03 | − 0.017 | 0.08 | 0.03 | 0.02 | 0.007 | 0.56 | 0.03 | 0.02 | 0.007 | 0.04 | ||||||||||
GDF-15 | Growth/differentiation factor 15 | 0.006 | 0.59 | 0.002 | 0.83 | 0.09 | < 0.001 | 0.09 | < 0.001 | 0.078 | < 0.001 | 0.082 | < 0.001 | ||||||||||
OPN | Osteopontin | − 0.002 | 0.83 | − 0.01 | 0.26 | 0.04 | 0.001 | 0.03 | 0.05 | 0.04 | 0.008 | 0.02 | 0.23 | ||||||||||
IGFBP-1 | Insulin-like growth factor-binding protein 1 | − 0.045 | < 0.001 | − 0.052 | 0.001 | − 0.02 | 0.08 | − 0.04 | 0.002 | − 0.03 | 0.04 | -0.07 | < 0.001 | ||||||||||
IGFBP-2 | Insulin-like growth factor-binding protein 2 | − 0.046 | < 0.001 | − 0.054 | 0.002 | − 0.03 | 0.01 | − 0.04 | 0.002 | − 0.03 | 0.01 | -0.04 | 0.002 | ||||||||||
SOST | Sclerostin | − 0.004 | 0.63 | − 0.004 | 0.62 | 0.04 | 0.005 | 0.02 | 0.1 | 0.03 | 0.05 | 0.02 | 0.22 | ||||||||||
Total 25 (OH) vitamin-D | − 0.007 | 0.14 | − 0.003 | 0.5 | |||||||||||||||||||
Ferritin | 0.09 | < 0.001 | 0.1 | < 0.001 | |||||||||||||||||||
Transferrin | − 0.08 | 0.21 | − 0.09 | 0.15 | |||||||||||||||||||
CRP | C-Reactive Protein | 0.039 | < 0.001 | 0.045 | < 0.001 | 0.06 | < 0.001 | 0.06 | < 0.001 | 0.05 | < 0.001 | 0.05 | < 0.001 | ||||||||||
PTH | Parathyroid hormone | 0.07 | 0.010 | 0.06 | 0.02 | ||||||||||||||||||
Plasma calcium | 0.33 | 0.09 | 0.4 | 0.04 | 0.34 | 0.009 | 0.43 | 0.001 | 0.37 | 0.03 | 0.04 | 0.01 | |||||||||||
Osteocalcin | − 0.002 | 0.06 | − 0.002 | 0.03 | |||||||||||||||||||
ALAT | Alanine aminotransferase | 0.038 | 0.05 | 0.044 | 0.02 |