Table 1.
Phenotypic parameters (top); and selected properties of bone (femur metaphysis, femur diaphysis, L6 vertebra), as determined by uCT, three-point bending and compression testing.
| Canagliflozin effects | Diabetes effects | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Parameter | STZ+CA NA1 | STZ+VE H2 | CONT+CANA3 | CONT+VEH4 | PI (+T1D) | P2 (no T1D) | P3 (+CANA) | P4 (no CANA) | |
| (n=19) | (n=18) | (n=20) | (n=20) | 1 vs 2 | 3 vs 4 | 1 vs 3 | 2 vs 4 | ||
| Starting body weight |
gm | 22.63 (1.70) |
24.24 (1.76) |
25.53 (2.04) |
26.42 (2.33) |
0.030 8 |
NS | <.0001 | 0.0035 |
| Ending body weight |
gm | 20.54 (3.54) |
20.41 (2.21) |
26.79 (2.33) |
26.70 (2.59) |
NS | NS | <.0001 | <.0001 |
| Week 3 blood glucose |
mg/dL | 358.84 (72.30) |
520.94 (84.69) |
150.25 (18.65) |
153.35 (14.50) |
<.000 1 |
NS | <.0001 | <.0001 |
| Week 10 blood glucose (sac) |
mg/dL | 338.89 (131.45) |
525.18 (53.64) |
111.75 (18.50) |
101.25 (18.77) |
<.000 1 |
NS | <.0001 | <.0001 |
| CCR‡ | μg/mg | 445.16 (194) |
589.87 (402.42) |
164.20 (88.94) |
92.03 (37.65) |
NS | 0.003 | <.0001 | <.0001 |
|
Diaphysis/Cortic al Bone |
|||||||||
| Ma. V | mm3 | 0.67 (0.04) |
0.71 (0.06) |
0.59 (0.06) |
0.59 (0.06) |
0.079 8 |
NS | 0.0002 | <.0001 |
| Imin | mm4 | 0.05 (0.01) |
0.05 (0.01) |
0.06 (0.01) |
0.06 (0.01) |
NS | NS | <.0001 | <.0001 |
| Ct.AR (BArea) | mm2 | 0.57 (0.05) |
0.58 (0.07) |
0.72 (0.05) |
0.75 (0.05) |
NS | NS | <.0001 | <.0001 |
| Tt.AR (TArea) | mm2 | 1.09 (0.06) |
1.13 (0.07) |
1.18 (0.09) |
1.22 (0.09) |
NS | NS | 0.0024 | 0.004 |
| Ct.TMD | mgHA /cm3 |
1364.11 (11.29) |
1368.88 (17.53) |
1366.03 (22.23) |
1376.81 (12.90) |
NS | NS | NS | NS |
| Ct.Th | mm | 0.16 (0.01) |
0.16 (0.01) |
0.19 (0.01) |
0.20 (0.01) |
NS | 0.072 1 |
<.0001 | <.0001 |
| Ct.Po | % | 2.66 (0.31) |
2.64 (0.37) |
2.14 (0.45) |
2.02 (0.23) |
NS | NS | <.0001 | <.0001 |
| Length | mm | 13.68 (0.35) |
13.81 (0.29) |
14.11 (0.27) |
14.13 (0.26) |
NS | NS | <.0001 | 0.0029 |
| Bending strength | MPa | 235.77 (21.04) |
231.86 (40.36) |
268.02 (21.92) |
274.30 (24.39) |
NS | NS | 0.0016 | <.0001 |
| Modulus | GPa | 12.70 (1.42) |
12.62 (2.19) |
14.40 (1.89) |
14.16 (1.71) |
NS | NS | 0.0188 | 0.0337 |
| Toughness | N/mm | 1.55 (0.31) |
1.41 (0.42) |
2.45 (0.75) |
2.39 (0.68) |
NS | NS | <.0001 | <.0001 |
| Peak Moment | N.mm | 23.56 (3.15) |
24.32 (5.73) |
32.64 (4.48) |
35.52 (3.98) |
NS | 0.085 2 |
<.0001 | <.0001 |
| Rigidity | N/mm 2 |
597.28 (109.83) |
645.51 (175.22) |
865.61 (141.01) |
909.03 (155.10) |
NS | NS | <.0001 | <.0001 |
| Slendernessa | mm/m m2 |
12.60 (0.61) |
12.24 (0.75) |
12.02 (0.82) |
11.66 (0.77) |
NS | NS | 0.0703 | 0.0703 |
| Normalized PYD | mm | 0.01 (0.01) |
0.01 (0.01) |
0.04 (0.02) |
0.03 (0.02) |
NS | NS | <.0001 | 0.0002 |
|
Metaphysis/Trab ecular Bone |
|||||||||
| VOX-BV/TV | mm3 | 0.05 (0.01) |
0.04 (0.01) |
0.07 (0.01) |
0.08 (0.01) |
NS |
0.015 7 |
<.0001 | <.0001 |
| Conn.D‡ | mm−3 | 156.05 (53.98) |
155.16 (54.51) |
119.78 (25.60) |
141.07 (29.91) |
NS | NS | 0.0256 | NS |
| SMIb | -- | 2.03 (0.19) |
2.15 (0.21) |
2.39 (0.16) |
2.35 (0.14) |
NS | NS | <.0001 | 0.0023 |
| Tb.N | mm−1 | 3.30 (0.26) |
3.30 (0.27) |
3.68 (0.32) |
3.97 (0.29) |
NS |
0.004 7 |
0.0003 | <.0001 |
| Tb.Th | mm | 0.03 (0.00) |
0.03 (0.00) |
0.04 (0.00) |
0.04 (0.00) |
NS | NS | <.0001 | <.0001 |
| Tb.Sp | mm | 0.31 (0.02) |
0.31 (0.02) |
0.28 (0.03) |
0.26 (0.02) |
NS |
0.018 4 |
0.0003 | <.0001 |
| Tb.TMD | mgHA /cm3 |
951.89 (21.87) |
962.66 (31.67) |
1012.59 (25.13) |
1046.00 (21.17) |
NS |
0.000 1 |
<.0001 | <.0001 |
| L6 Vertebra # | |||||||||
| Tb.BV/TV | mm3 | 0.15 (0.03) |
0.15 (0.03) |
0.20 (0.03) |
0.21 (0.02) |
NS | NS | 0.001 |
<0.000 1 |
| Tb.TMD | mgHA /cm3 |
704.90 (11.81) |
715.80 (44.77) |
816.70 (16.10) |
807.70 (14.76) |
NS | NS |
<0.000 1 |
<0.000 1 |
| Force | N | 10.53 (2.82) |
11.63 (5.75) |
20.84 (6.23) |
22.20 (3.73) |
NS | NS |
<0.000 1 |
<0.000 1 |
| Stress | MPa | 27.99 (8.03) |
27.87 (9.13) |
37.89 (10.84) |
38.62 (6.26) |
NS | NS | 0.094 | 0.055 |
A comparison of all parameters (mean ± SD) between the four groups is shown. Pairwise p-values are indicated, as follows: PI, STZ+CANA vs. STZ+VEH; P2, CONT+CANA vs. CONT+VEH; P3, STZ+CANA vs CONT+CANA; P4, STZ+VEH vs. CONT+VEH.
Slenderness is the ratio of the length to the total cross-sectional area of the femur mid-shaft.
Structural model index characterizes the shape of trabecular bone (1: plate-like; 3: rod-like).
Variables were log-transformed due to violation of the normality assumption.
Vertebral analyses conducted on n=10 mice per group.
Abbreviations: CCR, urine Calcium to Creatinine ratio; Alphabetically listed: BV/TV, bone volume/tissue volume; Conn.D, connectivity density; Ct.Ar, cortical area; Ct.Po, cortical porosity; Ct.Th, cortical thickness; Ct.TMD, cortical tissue mineral density; Force, peak force in compression; Imin, minimal moment of inertia; Ma.V, marrow volume; PYD, post yield deflection; SMI, structural model index; Stress, peak force per area; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness; Tb.TMD, trabecular tissue mineral density; Tt.Ar, total cross-sectional area. Significant differences (p<0.05) are highlighted in bold font; p<0.10 are also shown. NS = no significant difference.