Introduction
Methods
Study population and design
Measures
Diabetes status
T2DM subgroups
HR-pQCT imaging
Image analysis of HR-pQCT scans
Covariates
Statistical analyses
Results
NGM (n = 279) | PDM (n = 66) | T2DM (n = 65) | p value | |
---|---|---|---|---|
Age in years | 56.8 (8.3) | 59.9 (8.0) | 62.5 (7.1) | < 0.001* |
Female sex | 152 (54.5) | 34 (51.5) | 24 (36.9) | 0.04* |
BMI, kg/m2 | 25.8 (3.6) | 28.6 (4.2) | 30.0 (5.5) | < 0.001* |
Level of education (n = 404) | ||||
- Low | 67 (24.1) | 25 (40.3) | 29 (45.3) | 0.002* |
- Medium | 86 (30.9) | 18 (29.0) | 19 (29.7) | |
- High | 125 (45.0) | 19 (30.6) | 16 (25.0) | |
Smoking status (n = 407) | ||||
- Never | 113 (40.5) | 17 (26.2) | 21 (33.3) | 0.12 |
- Former | 134 (48.0) | 42 (64.6) | 37 (58.7) | |
- Current | 32 (11.5) | 6 (9.2) | 5 (7.9) | |
Alcohol use (n = 407) | ||||
- None | 38 (13.6) | 9 (13.8) | 14 (22.2) | 0.51 |
- Low | 161 (57.7) | 37 (56.9) | 31 (49.2) | |
- High | 80 (28.7) | 19 (29.2) | 18 (28.6) | |
History of CVD (n = 400) | 31 (11.3) | 12 (18.5) | 19 (31.7) | < 0.001* |
MVPA in hours per week (n = 363) | 6.9 (4.9) | 5.3 (3.3) | 4.3 (4.2) | < 0.001* |
Fracture ≥ 50 years (n = 340) | 15 (6.0) | 6 (10.5) | 1 (3.0) | 0.32 |
Antihyperglycemic drugs | n/a | n/a | 41 (63.1) | n/a |
Insulin | n/a | n/a | 12 (18.5) | n/a |
Thiazolidinedione | n/a | n/a | 0 | n/a |
HbA1c in mmol/mol (n = 408) | 36.3 (3.9) | 38.8 (4.6) | 50.9 (8.5) | < 0.001* |
HbA1c in % (n = 408) | 5.5 (0.4) | 5.7 (0.4) | 6.8 (0.8) | < 0.001* |
Diabetes duration in years | n/a | n/a | 3.0 [0.0–8.0] | n/a |
Retinopathy (n = 382) | 0 | 0 | 5 (7.7) | n/a |
Impaired vibration sensation (n = 359) | 12 (4.8) | 2 (3.6) | 9 (16.7) | 0.004* |
Nephropathy (n = 349) | 17 (7.1) | 6 (9.8) | 8 (16.3) | 0.11 |
eGFR < 60 mL/min (402) | 5 (1.8) | 3 (4.5) | 7 (11.1) | 0.002* |
Micro-albumin in urine > 30 mg/24 h (n = 356) | 13 (5.3) | 5 (8.2) | 6 (12.0) | 0.20 |
MVD (n = 297) | 27 (13.8) | 8 (16.3) | 19 (36.5) | 0.001* |
Quality grade scan radius | ||||
- 1 | 49 (17.6) | 9 (13.6) | 13 (20.0) | 0.58 |
- 2 | 130 (46.6) | 30 (45.5) | 34 (52.3) | |
- 3 | 100 (35.8) | 27 (40.9) | 18 (27.7) |
Bone parameters according to diabetes status
Distal radius | Distal tibia | |||||||
---|---|---|---|---|---|---|---|---|
NGM (n = 279) | PDM (n = 66) | T2DM (n = 65) | p value | NGM (n = 140) | PDM (n = 25) | T2DM (n = 33) | p value | |
Cross-sectional area (mm2) | 328.0 (79.9) | 333.6 (77.8) | 340.4 (81.1) | 0.51 | 777.5 (154.6) | 798.2 (151.0) | 828.9 (171.8) | 0.23 |
Volumetric bone mineral density | ||||||||
Total vBMD (mgHA/cm3) | 301.0 (62.1) | 305.4 (58.2) | 305.1 (71.6) | 0.82 | 284.6 (51.7) | 285.8 (51.6) | 300.2 (50.3) | 0.29 |
Trabecular vBMD (mgHA/cm3) | 163.7 (39.7) | 165.3 (32.3) | 166.8 (39.6) | 0.82 | 175.9 (36.8) | 176.8 (28.5) | 185.4 (36.1) | 0.38 |
Cortical vBMD (mgHA/cm3) | 852.1 (74.0) | 850.3 (70.2) | 836.5 (84.0) | 0.32 | 834.5 (56.0) | 828.1 (67.1) | 838.2 (54.7) | 0.80 |
Microarchitecture | ||||||||
Trabecular number (1/mm) | 1.93 (0.32) | 2.00 (0.26) | 1.96 (0.34) | 0.27 | 1.94 (0.34) | 1.86 (0.28) | 2.08 (0.36) | 0.03* |
Trabecular thickness (mm) | 0.07 (0.01) | 0.07 (0.01) | 0.07 (0.01) | 0.53 | 0.08 (0.01) | 0.08 (0.01) | 0.07 (0.01) | 0.26 |
Trabecular separation (mm) | 0.47 (0.15) | 0.44 (0.07) | 0.46 (0.14) | 0.32 | 0.46 (0.10) | 0.47 (0.08) | 0.42 (0.09) | 0.10 |
Cortical thickness (mm) | 0.75 (0.21) | 0.77 (0.20) | 0.77 (0.25) | 0.60 | 1.13 (0.31) | 1.15 (0.33) | 1.24 (0.31) | 0.21 |
Cortical pore volume (mm3) | 14.6 (8.2) | 15.3 (6.2) | 17.6 (8.1) | 0.02* | 79.4 (33.1) | 83.3 (28.6) | 94.4 (37.4) | 0.07 |
Cortical porosity (%) | 2.83 (1.45) | 2.81 (0.94) | 3.29 (1.29) | 0.05* | 7.63 (2.80) | 7.92 (2.78) | 8.00 (2.69) | 0.74 |
Cortical pore diameter (mm) | 0.17 (0.02) | 0.17 (0.02) | 0.18 (0.02) | 0.01* | 0.19 (0.02) | 0.19 (0.02) | 0.19 (0.02) | 0.62 |
Bone strength | ||||||||
Stiffness (kN/mm) | 93.9 (28.0) | 95.1 (24.8) | 97.1 (25.7) | 0.69 | 234.7 (63.2) | 244.8 (56.7) | 260.6 (64.6) | 0.10 |
Failure load (N) | 4480 (1318) | 4556 (1174) | 4643 (1206) | 0.63 | 11,157 (2926) | 11,587 (2648) | 12,390 (3035) | 0.09 |
Distal radius | Distal tibia | |||||
---|---|---|---|---|---|---|
NGM (n = 246) | PMD (n = 56) | T2DM (n = 52) | NGM (n = 127) | PDM (n = 21) | T2DM (n = 28) | |
B (95% CI) | B (95% CI) | B (95% CI) | B (95% CI) | |||
Cross-sectional area (mm2) | Ref | 3.9 (− 12.1 to 19.8) | − 14.0 (− 31.9 to 3.8) | Ref | − 10.0 (− 66.3 to 46.4) | − 72.0* (− 128.2 to − 15.8) |
Volumetric bone mineral density | ||||||
Total vBMD (mgHA/cm3) | Ref | − 5.3 (− 23.2 to 12.6) | 7.3 (− 12.7 to 27.3) | Ref | − 5.5 (− 27.4 to 16.5) | 4.2 (− 17.7 to 26.0) |
Trabecular vBMD (mgHA/cm3) | Ref | − 5.5 (− 15.7 to 4.7) | − 2.7 (− 14.1 to 8.8) | Ref | − 4.4 (− 19.5 to 10.7) | − 4.3 (− 19.3 to 10.8) |
Cortical vBMD (mgHA/cm3) | Ref | − 0.9 (− 21.1 to 19.3) | 12.9 (− 9.7 to 35.5) | Ref | 1.1 (− 21.8 to 23.9) | 12.4 (− 10.3 to 35.2) |
Microarchitecture | ||||||
Trabecular number (1/mm) | Ref | 0.03 (− 0.06 to 0.12) | − 0.04 (− 0.14 to 0.06) | Ref | − 0.16* (− 0.30 to − 0.02) | − 0.02 (− 0.16 to 0.12) |
Trabecular thickness (mm) | Ref | − 0.003 (− 0.007 to 0.000) | 0.000 (− 0.004 to 0.004) | Ref | 0.004 (− 0.001 to 0.010) | − 0.001 (− 0.007 to 0.004) |
Trabecular separation (mm) | Ref | − 0.01 (− 0.05 to 0.03) | 0.01 (− 0.03 to 0.06) | Ref | 0.04 (− 0.00 to 0.08) | 0.01 (− 0.03 to 0.05) |
Cortical thickness (mm) | Ref | − 0.01 (− 0.06 to 0.05) | 0.02 (− 0.04 to 0.09) | Ref | − 0.04 (− 0.17 to 0.09) | 0.01 (− 0.12 to 0.14) |
Cortical pore volume (mm3) | Ref | − 1.32 (− 3.40 to 0.77) | 0.46 (− 1.88 to 2.79) | Ref | − 3.03 (− 17.6 to 11.6) | − 2.19 (− 16.7 to 12.3) |
Cortical porosity (%) | Ref | − 0.29 (− 0.67 to 0.09) | 0.07 (− 0.36 to 0.49) | Ref | 0.04 (− 1.19 to 1.27) | − 0.01 (− 1.23 to 1.21) |
Cortical pore diameter (mm) | Ref | − 0.005 (− 0.011 to 0.001) | 0.006 (− 0.001 to 0.013) | Ref | 0.009 (− 0.001 to 0.018) | 0.004 (− 0.006 to 0.014) |
Bone strength | ||||||
Stiffness (kN/mm) | Ref | − 1.8 (− 6.8 to 3.1) | − 2.8 (− 8.3 to 2.7) | Ref | − 2.0 (− 22.3 to 18.3) | − 15.1 (− 35.3 to 5.1) |
Failure load (N) | Ref | − 70.3 (− 298.6 to 158.0) | − 130.7 (− 386.3 to 125.0) | Ref | − 145.0 (− 1067.6 to 777.6) | − 732.6 (− 1652.6 to 187.5) |
Bone parameters of type 2 diabetes subgroups
Distal radius | HbA1c ≤ 7% (n = 44) | HbA1c > 7% (n = 21) | Diabetes duration ≤ 5 years (n = 40#) | Diabetes duration > 5 years (n = 21#) | MVD− (n = 33#) | MVD+ (n = 19#) |
Age in years, mean (SD) | 62.6 (7.3) | 62.4 (7.0) | 62.3 (7.4) | 62.8 (6.6) | 60.7 (7.7) | 65.8 (5.1)c |
Female sex, no. (%) | 16 (36.4) | 8 (38.1) | 16 (41.0) | 5 (23.8) | 18 (54.5) | 4 (21.1)c |
BMI (kg/m2), mean (SD) | 29.9 (5.2) | 30.2 (6.1) | 30.4 (5.8) | 29.6 (5.3) | 29.4 (6.1) | 30.8 (4.3) |
HbA1c in %, mean (SD) | 6.4 (0.4) | 7.7 (0.6)a | 6.6 (0.7) | 7.1 (0.7)b | 6.7 (0.6) | 7.0 (0.9) |
HbA1c in mmol/mol, mean (SD) | 46.2 (4.6) | 60.8 (6.1)a | 48.5 (7.9) | 54.4 (8.1)b | 49.5 (6.6) | 52.9 (10.1) |
Diabetes duration in years, median [IQR] | 1.5 [6.0] | 7.0 [11.0]a | 1.0 [3.0] | 11.0 [8.0]b | 2.0 [7.0] | 3.5 [14.0] |
Insulin use, no. (%) | 4 (9.1) | 8 (38.1)a | 2 (5.0) | 9 (42.9)b | 4 (12.1) | 5 (26.3) |
MVD, no. (%) | 10 (28.6) | 9 (52.9) | 10 (30.3) | 8 (50.0) | n/a | n/a |
Distal tibia | HbA1c ≤ 7% (n = 22) | HbA1c > 7% (n = 11) | Diabetes duration ≤ 5 years (n = 20#) | Diabetes duration > 5 years (n = 10#) | MVD− (n = 14#) | MVD+ (n = 12#) |
Age in years, mean (SD) | 64.4 (6.9) | 62.5 (6.8) | 63.8 (7.0) | 65.2 (6.7) | 61.4 (8.4) | 66.5 (4.0) |
Female sex, no. (%) | 3 (13.6) | 5 (45.5) | 4 (20.0) | 2 (20.0) | 6 (42.9) | 0 (0.0)c |
BMI (kg/m2), mean (SD) | 29.7 (5.7) | 27.7 (4.3) | 29.4 (4.8) | 27.0 (5.3) | 29.2 (5.9) | 29.6 (5.1) |
HbA1c in %, mean (SD) | 6.3 (0.4) | 7.8 (0.6)a | 6.5 (0.9) | 7.2 (0.7)b | 6.7 (0.6) | 6.7 (1.0) |
HbA1c in mmol/mol, mean (SD) | 45.2 (4.7) | 61.3 (7.0)a | 48.1 (9.9) | 55.5 (7.9)b | 49.6 (6.5) | 50.3 (10.5) |
Diabetes duration in years, median [IQR] | 2.0 [5.0] | 7.0 [16.0] | 1.0 [3.0] | 10.0 [13.0]b | 3.5 [6.0] | 1.5 [7.0] |
Insulin use, no. (%) | 2 (9.1) | 3 (27.3) | 1 (5.0) | 4 (40.0)b | 1 (7.1) | 1 (8.3) |
MVD, no. (%) | 8 (47.1) | 4 (44.4) | 8 (47.1) | 4 (57.1) | n/a | n/a |
Distal radius | Distal tibia | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
HbA1c ≤ 7% (n = 44) | HbA1c > 7% (n = 21) | DD ≤ 5 years (n = 40) | DD > 5 years (n = 21) | MVD− (n = 33) | MVD+ (n = 19) | HbA1c ≤ 7% (n = 22) | HbA1c > 7% (n = 11) | DD ≤ 5 years (n = 20) | DD > 5 years (n = 10) | MVD− (n = 14) | MVD+ (n = 12) | |
Cross-sectional area (mm2) | 334.9 (76.7) | 352.0 (90.6) | 324.8 (78.2) | 376.7b (83.0) | 314.3 (68.7) | 381.0c (89.4) | 845.8 (164.4) | 795.0 (189.1) | 842.0 (162.1) | 849.9 (188.5) | 788.1 (139.1) | 923.2c (140.9) |
vBMD | ||||||||||||
Total vBMD (mgHA/cm3) | 311.9 (77.2) | 290.9 (57.3) | 307.6 (66.6) | 309.4 (76.5) | 303.5 (75.6) | 292.3 (73.2) | 304.4 (50.2) | 291.9 (52.0) | 291.5 (56.8) | 314.0 (34.3) | 300.6 (58.2) | 298.8 (44.3) |
Trabecular vBMD (mgHA/cm3) | 163.7 (42.5) | 173.5 (32.7) | 165.6 (40.7) | 173.0 (38.3) | 164.2 (45.7) | 171.4 (35.9) | 187.1 (39.0) | 182.2 (30.8) | 182.4 (38.7) | 195.1 (28.9) | 189.4 (33.5) | 191.1 (35.8) |
Cortical vBMD (mgHA/cm3) | 850.6 (83.4) | 806.9a (79.1) | 847.5 (61.8) | 833.0 (86.2) | 842.5 (83.8) | 806.1 (92.0) | 846.1 (51.1) | 822.5 (60.6) | 827.3 (57.8) | 850.8 (50.3) | 825.0 (63.9) | 832.3 (40.6) |
Microarchitecture | ||||||||||||
Trabecular number (1/mm) | 1.90 (0.34) | 2.08a (0.31) | 1.92 (0.36) | 2.04 (0.31) | 1.91 (0.36) | 2.00 (0.32) | 2.02 (0.40) | 2.19 (0.26) | 2.08 (0.38) | 2.13 (0.35) | 2.09 (0.32) | 2.16 (0.38) |
Trabecular thickness (mm) | 0.07 (0.01) | 0.07 (0.01) | 0.07 (0.01) | 0.07 (0.01) | 0.07 (0.01) | 0.07 (0.01) | 0.08 (0.01) | 0.07a (0.01) | 0.07 (0.01) | 0.08 (0.01) | 0.08 (0.01) | 0.07 (0.01) |
Trabecular separation (mm) | 0.48 (0.16) | 0.42 (0.09) | 0.48 (0.16) | 0.43 (0.08) | 0.48 (0.18) | 0.44 (0.09) | 0.44 (0.10) | 0.39 (0.06) | 0.42 (0.09) | 0.41 (0.10) | 0.41 (0.07) | 0.40 (0.09) |
Cortical thickness (mm) | 0.81 (0.26) | 0.68 (0.21) | 0.77 (0.20) | 0.80 (0.30) | 0.74 (0.24) | 0.72 (0.26) | 1.28 (0.31) | 1.15 (0.31) | 1.21 (0.38) | 1.29 (0.21) | 1.20 (0.39) | 1.26 (0.27) |
Cortical pore volume (mm3) | 17.4 (8.4) | 18.2 (7.4) | 18.2 (7.8) | 17.8 (8.6) | 15.5 (6.2) | 20.4c (9.7) | 96.1 (39.3) | 91.1 (34.7) | 98.9 (39.6) | 94.2 (35.8) | 93.6 (34.4) | 108.1 (39.4) |
Cortical porosity (%) | 3.08 (1.22) | 3.71 (1.38) | 3.43 (1.31) | 3.06 (1.25) | 3.13 (1.30) | 3.69c (1.30) | 7.86 (2.77) | 8.28 (2.58) | 8.43 (2.76) | 7.73 (2.62) | 8.49 (2.78) | 8.46 (2.54) |
Cortical pore diameter (mm) | 0.18 (0.02) | 0.17 (0.02) | 0.18 (0.02) | 0.17 (0.02) | 0.18 (0.02) | 0.18 (0.02) | 0.19 (0.03) | 0.18 (0.02) | 0.18 (0.02) | 0.20 (0.04) | 0.19 (0.02) | 0.19 (0.03) |
Bone strength | ||||||||||||
Stiffness (kN/mm) | 98.7 (27.0) | 93.7 (22.7) | 94.6 (23.5) | 105.8 (26.9) | 91.0 (25.8) | 102.8 (22.5) | 271.9 (62.6) | 237.9 (65.4) | 257.8 (71.1) | 278.7 (56.5) | 250.4 (63.2) | 284.5 (52.7) |
Failure load (N) | 4701 (1269) | 4519 (1079) | 4515 (1107) | 5072 (1257) | 4353 (1219) | 4927 (1047) | 12,883 (2973) | 11,402 (3050) | 12,292 (3342) | 13,190 (2658) | 11,902 (2962) | 13,548 (2455) |
Distal radius | Distal tibia | |||||
---|---|---|---|---|---|---|
HbA1c > 7% (n = 21) | Diabetes duration > 5 years (n = 21) | MVD+ (n = 19) | HbA1c > 7% (n = 11) | Diabetes duration > 5 years (n = 10) | MVD+ (n = 12) | |
B (95% CI) | B (95% CI) | B (95% CI) | B (95% CI) | B (95% CI) | B (95% CI) | |
Cross-sectional area(mm2) | 18.2 (− 14.9 to 51.3) | 33.3 (− 2.5 to 69.1) | 39.4 (− 1.9 to 80.6) | 12.9 (− 106.4 to 132.1) | 4.6 (− 121.2 to 130.5) | 96.2 (− 36.0 to 228.5) |
vBMD | ||||||
Total vBMD (mgHA/cm3) | − 21.0 (− 58.3 to 16.9) | 5.7 (− 34.7 to 46.2) | − 19.3 (− 67.9 to 29.3) | − 1.7 (− 41.1 to 37.6) | 34.1 (− 2.0 to 70.2) | − 7.4 (− 51.2 to 36.4) |
Trabecular vBMD (mgHA/cm3) | 10.6 (− 8.5 to 29.8) | 10.0 (− 11.0 to 30.9) | − 6.0 (− 31.4 to 19.5) | − 0.1 (− 30.1–30.0) | 19.0 (− 9.1 to 47.1) | 1.9 (− 31.7 to 35.6) |
Cortical vBMD (mgHA/cm3) | − 44.4* (− 85.4 to − 3.4) | − 13.4 (− 54.1 to 27.2) | − 33.5 (− 87.1 to 20.1) | − 15.8 (− 58.3 to 26.8) | 26.2 (− 15.4 to 67.8) | 0.6 (− 48.6 to 49.8) |
Microarchitecture | ||||||
Trabecular number (1/mm) | 0.19* (0.03 to 0.34) | 0.17* (0.03 to 0.34) | 0.09 (− 0.12 to 0.29) | 0.27* (0.01 to 0.53) | 0.17 (− 0.09 to 0.42) | 0.10 (− 0.23 to 0.42) |
Trabecular thickness (mm) | − 0.001 (− 0.007 to 0.005) | − 0.002 (− 0.008 to 0.005) | − 0.005 (− 0.013 to 0.003) | − 0.010* (− 0.018 to − 0.002) | 0.002 (− 0.007 to 0.011) | − 0.002 (− 0.014 to 0.009) |
Trabecular separation (mm) | − 0.06 (− 0.12 to 0.01) | − 0.06 (− 0.13 to 0.01) | − 0.03 (− 0.12 to 0.06) | − 0.06 (− 0.13 to 0.00) | − 0.04 (− 0.11 to 0.02) | − 0.02 (− 0.09 to 0.06) |
Cortical thickness (mm) | − 0.13* (− 0.26 to − 0.00) | 0.03 (− 0.11 to 0.17) | − 0.05 (− 0.21 to 0.11) | − 0.02 (− 0.24 to 0.20) | 0.14 (− 0.07 to 0.35) | − 0.05 (− 0.31 to 0.21) |
Cortical pore volume (mm3) | 0.94 (− 3.01 to 4.90) | − 0.57 (− 4.77 to 3.63) | 2.44 (− 2.41 to 7.29) | 9.89 (− 19.8 to 39.5) | − 3.34 (− 34.3 to 27.7) | − 4.89 (− 41.7 to 31.9) |
Cortical porosity (%) | 0.65* (0.06 to 1.23) | − 0.29 (− 0.95 to 0.36) | 0.29 (− 0.45 to 1.04) | 0.41 (− 1.78 to 2.61) | − 0.91 (− 3.15 to 1.34) | − 0.48 (− 3.13 to 2.18) |
Cortical pore diameter (mm) | − 0.01 (− 0.02 to 0.00) | − 0.01 (− 0.02 to 0.00) | 0.00 (− 0.01 to 0.01) | − 0.02 (− 0.04 to 0.00) | 0.01 (− 0.01 to 0.03) | − 0.01 (− 0.03 to 0.02) |
Bone strength | ||||||
Stiffness (kN/mm) | − 4.4 (− 13.9 to 5.0) | 5.9 (− 4.4 to 16.1) | − 0.9 (− 12.0 to 10.2) | − 10.4 (− 51.2 to 30.4) | 24.5 (− 15.0 to 64.1) | 15.8 (− 27.3 to 58.9) |
Failure load (N) | − 158.6 (− 596.9 to 279.6) | 308.3 (− 166.4 to 783.0) | − 20.7 (− 533.1 to 491.7) | − 344.5 (− 2261.0 to 1571.9) | 1103.8 (− 753.4 to 2961.1) | 824.4 (− 1186.6 to 2835.4) |