Introduction
Materials and Methods
Study Population
Dietary Intake and Serum 25(OHD) Level
Loop Diuretics
Assessment of Co-variables
Outcome Assessment
Statistical Analyses
Results
Population Characteristics
Total population (n = 6990) | LD ever-users (n = 543) | LD never-users (n = 6447) | p value LD ever- versus never-users | |
---|---|---|---|---|
Age (years)b | 65.0 [57.0–99.0] | 77.0 [52.0–99.0] | 64.0 [51.0–97.0] | < 0.001* |
Sex (%women) | 3985 (57.0) | 309 (56.9) | 3675 (57.0) | 0.92 |
BMI (kg/cm2)a | 27.6 (4.1) | 28.9 (4.7) | 27.5 (4.7) | 0.002* |
Cohort (%) | < 0.001* | |||
RS-I | 2799 (40.0) | 437 (80.5) | 2360 (36.6) | |
RS-II | 980 (14.0) | 62 (11.4) | 918 (14.2) | |
RS-III | 3211 (46.0) | 44 (8.1) | 3167 (49.1) | |
Loop diuretics use (%ever use) | 543 (7.8) | 543 (100) | 0 | NA |
Duration (days)a | NA | 194 [40–893] | 0 | |
25(OH)D (nmol/l)b | 54.4 [36.5–76.0] | 42.3 [28.8–62.3] | 55.4 [37.2–76.7] | < 0.001* |
Cutoff (%) | < 0.001* | |||
< 50 nmol/L | 2580 (44.2) | 247 (45.5) | 2333 (36.2) | 0.41 |
> 50 nmol/L | 3257 (55.8) | 156 (28.7) | 3101 (48.1) | |
Season measurement (%) | ||||
Spring | 1928 (27.6) | 147 (27.0) | 1854 (28.8) | |
Summer | 1143 (16.4) | 82 (15.1) | 1107 (17.2) | |
Autumn | 2219 (31.7) | 177 (32.5) | 2126 (33.0) | |
Winter | 1432 (20.5) | 138 (25.4) | 1360 (21.0) | |
Dietary calcium intake (mg/day)a | 1126.5 (388.9) | 1189.2 (394.1) | 1120.8 (394.1) | 0.81 |
Tertiles (%) | ||||
< 950.0 mg/day | 1691 (24.2) | 103 (19.0) | 1588 (24.6) | |
950–1200 mg/day | 1504 (21.5) | 120 (22.1) | 1384 (21.5) | |
> 1200 mg/day | 1795 (25.7) | 186 (34.3) | 2609 (25.0) | |
Lumbar spine TBSa | 1.24 (0.13) | 1.17 (0.12) | 1.25 (0.12) | 0.32 |
Femoral neck bone mass density (g/cm2)a | 0.91 (0.15) | 0.86 (0.15) | 0.91 (0.15) | 0.98 |
Lumbar spine bone mass density (g/cm2)a | 1.14 (0.21) | 1.15 (0.22) | 1.14 (0.20) | 0.40 |
Smoking (%) | ||||
Never smoker | 2080 (29.8) | 157 (28.9) | 1921 (29.8) | 0.003* |
Current smoker | 1358 (19.4) | 58 (10.6) | 1302 (20.2) | |
Former, non-smoker | 3506 (50.2) | 319 (58.8) | 3185 (49.4) | |
Pack-yearsa | 9.4 (18.6) | 20.3 (28.0) | 8.5 (28.0) | < 0.001* |
Education category (%) | ||||
Low education | 3575 (51.6) | 319 (58.7) | 3256 (50.9) | < 0.001* |
Higher education | 3353 (48.4) | 219 (40.3) | 3134 (49.1) | |
Alcohol intake (g/day)b | 7.3 [0.8–20.0] | 3.1 [0.1–15.7] | 7.9 [0.9–20.0] | 0.11 |
PA (MET h/week)b | 70.5 [39.4–103.9] | 70.8 [47.6–100.1] | 70.4 [38.5–104.4] | 0.84 |
Energy intake (kcal/day)a | 2176.6 (710.2) | 1956.9 (533.8) | 2195.2 (533.8) | < 0.001* |
Comorbidities (%yes) | 1112 (15.9) | 150 (27.6) | 963 (14.9) | < 0.001* |
CHD | 315 (4.5) | 69 (12.7) | 246 (3.8) | |
Stroke | 129 (1.8) | 13 (2.4) | 116 (1.8) | |
DM | 790 (11.3) | 98 (18.0) | 691 (10.7) |
Model 1 | Model 2 | Model 3 | |
---|---|---|---|
β (95%CI) | β (95%CI) | β (95%CI) | |
LS-TBS (6476)a | |||
LD never-use (5972) | Reference | Reference | Reference |
LD past-use (n = 310) | − 0.031 [− 0.044; − 0.017]* | − 0.019 [− 0.033; − 0.006]* | − 0.025 [− 0.038; − 0.012]* |
LD current-use (n = 194) | − 0.018 [− 0.034; − 0.001]* | − 0.011 [− 0.028; 0.006] | − 0.015 [− 0.032; 0.002] |
Duration of LD-use categoriesb | |||
Never-users (n = 5972) | Reference | Reference | Reference |
Current-users 1–120 days (n = 37) | − 0.008 [− 0.027; 0.011] | − 0.0005 [− 0.043; 0.042] | − 0.003 [− 0.044; 0.039] |
Current-users 121–365 days (n = 27) | − 0.026 [− 0.048; 0.003] | − 0.026 [− 0.070; 0.018] | − 0.041 [− 0.084; 0.002] |
Current-users > 365 days (n = 310) | − 0.019 [− 0.039; 0.001] | − 0.010 [− 0.031; 0.010] | − 0.013 [− 0.032; 0.007] |
LS-BMD (n = 6677) | |||
LD never-use (6146) | Reference | Reference | Reference |
LD past-use (n = 321) | 0.048 [0.026; 0.071]* | 0.029 [0.006; 0.052]* | 0.038 [0.016; 0.060]* |
LD current-use (n = 210) | 0.037 [0.010; 0.065]* | 0.021 [− 0.008; 0.050] | 0.025 [− 0.003; 0.052] |
Duration of LD-use categoriesb | |||
Never-users (n = 6146) | Reference | Reference | Reference |
Current-users 1–120 days (n = 41) | 0.020 [− 0.040; 0.081] | 0.012 [− 0.059; 0.083] | 0.014 [− 0.054; 0.082] |
Current-users 121–365 days (n = 32) | 0.072 [0.004; 0.140]* | 0.068 [− 0.003; 0.139] | 0.075 [0.007; 0.143]* |
Current-users > 365 days (n = 137) | 0.034 [0.0004; 0.068]* | 0.012 [− 0.022; 0.047] | 0.016 [− 0.017; 0.049] |
FN-BMD (n = 6908) | |||
LD never-use (6376) | Reference | Reference | Reference |
LD past-use (n = 319) | 0.016 [0.001; 0.031]* | 0.006 [− 0.009; 0.021] | 0.010 [− 0.005; 0.025] |
LD current-use (n = 213) | 0.006 [− 0.012; 0.024] | − 0.006 [− 0.025; 0.013] | − 0.006 [− 0.024; 0.013] |
Duration of LD-use categoriesb | |||
Never-users (n = 6376) | Reference | Reference | Reference |
Current-users 1–120 days (n = 44) | 0.020 [− 0.019; 0.058] | 0.024 [− 0.021; 0.069] | 0.021 [− 0.025; 0.067] |
Current-users 121–365 days (n = 32) | 0.035 [− 0.011; 0.080] | 0.019 [− 0.028; 0.066] | 0.023 [− 0.023; 0.069] |
Current-users > 365 days (n = 137) | − 0.005 [− 0.027; 0.018] | − 0.019 [− 0.042; 0.003] | − 0.018 [− 0.040; 0.004] |
Loop Diuretics and LS-TBS
Loop Diuretics and LS-BMD
Loop Diuretics and FN-BMD
Serum 25(OH)D Level and Dietary Calcium Intake in the Association of the Use of Loop Diuretics and FN-BMD, LS-BMD and LS-TBS
25(OH)D ≤20 nmol/l (n = 302) | 25(OH)D 20–50 nmol/l (n = 2240) | 25(OH)D ≥50 nmol/l (n = 3225) | p value interaction term | |
---|---|---|---|---|
β (95%CI) | β (95%CI) | β (95%CI) | ||
LS-TBS (6476)a | ||||
LD never-use | Reference | Reference | Reference | 0.04** |
LD past-use (n = 310) | − 0.012 [− 0.036; 0.013] | − 0.031 [− 0.096; 0.034] | − 0.036 [− 0.060; − 0.013]* | |
LD current-use (n = 194) | 0.001 [− 0.036; 0.039] | − 0.029 [− 0.099; 0.041] | − 0.014 [− 0.046; 0.017] |
25(OH)D ≤20 nmol/l (n = 287) | 25(OH)D 20–50 nmol/l (n = 2146) | 25(OH)D ≥50 nmol/l (n = 3108) | p value interaction term | |
---|---|---|---|---|
β (95%CI) | β (95%CI) | β (95%CI) | ||
LS-BMD (n = 6677) | ||||
LD never-use | Reference | Reference | Reference | 0.30 |
LD past-use (n = 321) | 0.079 [− 0.054; 0.148] | 0.003 [− 0.034; 0.041] | 0.038 [− 0.003; 0.080] | |
LD current-use (n = 210) | − 0.052 [− 0.157; 0.053] | 0.044 [0.002; 0.087]* | 0.039 [− 0.016; 0.095] |
25(OH)D ≤20 nmol/l (n = 267) | 25(OH)D 20–50 nmol/l (n = 2054) | 25(OH)D ≥50 nmol/l (n = 3056) | p value interaction term | |
---|---|---|---|---|
β (95%CI) | β (95%CI) | β (95%CI) | ||
FN-BMD (n = 6908) | ||||
LD never-use | Reference | Reference | Reference | 0.13 |
LD past-use (n = 319) | 0.027 [− 0.037; 0.092] | − 0.006 [− 0.031; 0.019] | 0.008 [− 0.020; 0.036] | |
LD current-use (n = 213) | − 0.022 [− 0.089; 0.045] | − 0.004 [− 0.031; 0.023] | 0.015 [− 0.021; 0.051] |
Dietary calcium intake ≤ 950 mg/day (n = 1822) | Dietary calcium intake 950–1,200 mg/day (n = 1600) | Dietary calcium intake ≥ 1200 mg/day (n = 1875) | p value interaction term | |
---|---|---|---|---|
β (95%CI) | β (95%CI) | β (95%CI) | ||
LS-TBS (6476)a | ||||
LD never-use | Reference | Reference | Reference | 0.58 |
LD past-use (n = 310) (yes/no) | − 0.018 [− 0.047; 0.010] | − 0.022 [− 0.050; 0.005] | − 0.015 [− 0.037; 0.007] | |
LD current-use (n = 194) (yes/no) | − 0.009 [− 0.044; 0.025] | 0.007 [− 0.028; 0.043] | − 0.015 [− 0.043; 0.013] | |
Dietary calcium intake ≤ 950 mg/day (n = 1732) | Dietary calcium intake 950–1200 mg/day (n = 1548) | Dietary calcium intake ≥ 1200 mg/day (n = 1838) | p value interaction term | |
β (95%CI) | β (95%CI) | β (95%CI) | ||
LS-BMD (n = 6677) | ||||
LD never-use | Reference | Reference | Reference | 0.87 |
LD past-use (n = 321) (yes/no) | 0.017 [− 0.034; 0.068] | 0.039 [− 0.008; 0.086] | 0.026 [− 0.012; 0.063] | |
LD current-use (n = 210) (yes/no) | 0.038 [− 0.023; 0.100] | 0.045 [− 0.016; 0.106] | 0.016 [− 0.031; 0.064] | |
Dietary calcium intake ≤ 950 mg/day (n = 1695) | Dietary calcium intake 950–1200 mg/day (n = 1509) | Dietary calcium intake ≥ 1200 mg/day (n = 1771) | p value interaction term | |
β (95%CI) | β (95%CI) | β (95%CI) | ||
FN-BMD (n = 6908) | ||||
LD never-use | Reference | Reference | Reference | 0.99 |
LD past-use (n = 319) (yes/no) | 0.001 [− 0.032; 0.034] | 0.087 [− 0.023; 0.039] | 0.008 [− 0.017; 0.034] | |
LD current-use (n = 213) (yes/no) | − 0.003 [− 0.043; 0.037] | 0.024 [− 0.015; 0.064] | − 0.025 [− 0.057; 0.007] |