Supplemental Tables
Supplemental Table S1: pQCT scan settings and analysis parameters.
Scan site / Scan Settings / AnalysisTibial metaphysis,
in vivo / Voxel size: 0.35 mm
Slice placement: Reference line at proximal tibia-fibula junction with 3 or 4 sequential slices distally / Contmode 2, automatic threshold
Peelmode 2, threshold 0.750 1/cm
Tibial diaphysis,
in vivo / Voxel size: 0.35 mm
Slice placement: 12% of total bone length distal to reference line set at the proximal end / Cortmode 2, threshold 0.930 1/cm
Radius diaphysis,
in vivo / Voxel size: 0.20 mm
Slice placement: 12% of total bone length proximal to the reference line set at the distal end / Cortmode 2, threshold 0.930 1/cm
Femoral diaphysis,
ex vivo / Voxel size: 0.15 mm
/ Contmode 2, threshold 0.446 1/cm
Peelmode 2, threshold 0.930 1/cm
Cortmode 2, threshold 0.930 1/cm
L3-L4 vertebra bodies, ex vivo / Voxel size: 0.20 mm
Distance between CT lines: 0.60 mm / Contmode 1, threshold 0.446 1/cm
Peelmode 2, 60% area
Cortmode 2, threshold 0.930 1/cm
L5-L6 cancellous cores, ex vivo / Voxel size: 0.10 mm
Distance between CT lines: 0.60 mm / Contmode 1, threshold 0.450 1/cm
Peelmode 1, 99% area
Cortmode 2, threshold 0.400 1/cm
Supplemental Table S2: Micro-CT scan settings and analysis parameters.
Distal Femur / T12 Vertebra / L6 Core / Humeral Cortical BeamX-ray
settings / Energy/Intensity / 70 kVp, 114 µA, 8 W / 70 kVp, 114 µA, 8 W / 55 kVp, 145 µA, 8 W / 70 kVp, 114 µA, 8 W
Calibration / 70 kVp, 0.5 mm Al, BH: 1200 mg HA/cm3 / 70 kVp, 0.5 mm Al, BH: 1200 mg HA/cm3 / 55 kVp, 0.5 mm Al, BH: 1200 mg HA/cm3 / 70 kVp, 0.5 mm Al, BH: 1200 mg HA/cm3
CT scanning parameters / FOV/Diameter / 35.2 mm / 35.2 mm / 10.2 mm / 10.2 mm
Voxel size / 34.4 µm / 34.4 µm / 34.4 µm / 5.0 µm
Volume of interest, number of slices / 200 slices starting proximal to caudal aspect of condyles / Whole specimen / Whole specimen / 1007 slices from middle part of beam
Contouring / Automatic / Automatic / Manual / Manual
Thresholding / Lower = 200
Upper = 1000 / Lower = 200
Upper = 1000 / Lower = 300
Upper = 1000 / Lower = 300
Upper = 1000
Supplemental Table S3. Serum calcium, phosphorus, PTH(1-84), 1,25-dihydroxivitamin D, and creatinine data. Data represent means ± SD, n = 14-17/group.
Time Point / Sham / Veh / ABL0.2 μg/kg/d / ABL
1 μg/kg/d / ABL
5 μg/kg/d
Serum Calcium (mg/dL)
Month -9 (pre-surgery) / 10.02 ± 0.35 / 10.01 ± 0.47 / 9.97 ± 0.52 / 9.88 ± 0.41 / 9.75 ± 0.41
Month 0 / 9.81 ± 0.38* / 10.23 ± 0.37 / 10.30 ± 0.33 / 10.26 ± 0.54 / 10.21 ± 0.54
Month 12 / 9.40 ± 0.33* / 9.84 ± 0.31 / 9.83 ± 0.39 / 9.84 ± 0.42 / 9.81 ± 0.41
Month 16 / 9.76 ± 0.22 / 10.12 ± 0.38 / 10.01 ± 0.49 / 10.14 ± 0.35 / 10.01 ± 0.51
Serum Phosphorus (mg/dL)
Month -9 (pre-surgery) / 4.02 ± 0.69 / 4.07 ± 0.56 / 4.64 ± 0.55* / 4.39 ± 0.72 / 4.10 ± 0.37
Month 0 / 4.54 ± 0.46* / 5.14 ± 0.70 / 5.39 ± 0.61 / 5.36 ± 0.73 / 5.12 ± 0.68
Month 12 / 3.75 ± 0.74 / 4.20 ± 0.55 / 4.33 ± 0.59 / 4.56 ± 0.55 / 4.15 ± 0.44
Month 16 / 4.99 ± 0.40 / 5.42 ± 0.56 / 5.40 ± 0.55 / 5.78 ± 0.66 / 5.28 ± 0.50
Serum PTH(1-84) (pg/mL)
Month -9 (pre-surgery) / 80.77 ± 46.35 / 69.62 ± 31.29 / 64.89 ± 20.80 / 80.83 ± 29.53 / 58.99 ± 24.19
Month 0 / 83.75 ± 40.94 / 72.02 ± 36.80 / 87.99 ± 32.42 / 93.27 ± 31.67 / 65.67 ± 29.94
Month 3 / 84.10 ± 49.96 / 91.55 ± 41.39 / 92.49 ± 27.70 / 91.67 ± 24.03 / 75.08 ± 27.45
Month 7.5 / 97.08 ± 39.83 / 92.47 ± 41.98 / 98.36 ± 34.51 / 93.51 ± 18.39 / 77.24 ± 26.35
Month 12 / 91.42 ± 35.35 / 101.01 ± 44.58 / 95.65 ± 40.36 / 97.68 ± 35.75 / 76.72 ± 15.12
Month 16 / 96.89 ± 50.95 / 99.88 ± 44.69 / 91.71 ± 27.02 / 91.86 ± 24.14 / 88.13 ± 20.86
Serum 1,25-dihydroxyvitamin D (pmol/L)
Month -9 (pre-surgery) / 756.0 ± 267.8 / 648.6 ± 143.3 / 601.2 ± 214.9 / 719.3 ± 273.3 / 670.9 ± 224.0
Month 0 / 669.4 ± 273.0 / 562.44 ± 257.0 / 576.1 ± 177.0 / 589.8 ± 257.4 / 587.3 ± 214.2
Month 3 / 593.2 ± 230.0 / 555.1 ± 209.0 / 579.0 ± 130.9 / 632.9 ± 165.4 / 663.7 ± 170.8
Month 7.5 / 759.0 ± 231.3 / 548.3 ± 168.2 / 692.5 ± 190.2 / 663.9 ± 246.3 / 695.5 ± 202.9
Month 12 / 539.3 ± 166.1 / 483.3 ± 124.2 / 507.6 ± 184.9 / 547.0 ± 164.6 / 562.7 ± 173.7
Month 16 / 700.7 ± 199.5 / 640.6 ± 121.3 / 697.4 ± 186.8 / 707.1 ± 158.9 / 730.5 ± 165.0
Serum Creatinine (mg/dL)
Month -9 (pre-surgery) / 0.87 ± 0.15 / 0.82 ± 0.10 / 0.88 ± 0.11 / 0.84 ± 0.10 / 0.84 ± 0.12
Month 0 / 0.88 ± 0.11 / 0.88 ± 0.08 / 0.99 ± 0.22 / 0.86 ± 0.09 / 0.93 ± 0.11
Month 12 / 0.83 ± 0.14 / 0.84 ± 0.13 / 0.87 ± 0.13 / 0.81 ± 0.11 / 0.87 ± 0.12
Month 16 / 0.93 ± 0.15 / 0.93 ± 0.14 / 0.96 ± 0.15 / 0.93 ± 0.17 / 0.98 ± 0.13
*P < 0.05 vs Veh control.ABL, abaloparatide;
Supplemental Table S4: Biochemical markers of bone turnover. Data represent means ± SD, n = 14-17/group.
Time Point / Sham / Veh / ABL0.2 μg/kg/d / ABL
1 μg/kg/d / ABL
5 μg/kg/d
Serum Procollagen 1 N-Terminal Peptide (P1NP, μg/mL)
Pre-surgery / 312.15 ± 116.0 / 264.4 ± 125.8 / 337.0 ± 180.0 / 289.1 ± 87.7 / 331.4 ± 170.4
Month 0 / 151.3 ± 59.0* / 511.2 ± 208.8 / 566.7 ± 196.0 / 537.8 ± 171.6 / 549.4 ± 201.2
Month 3 / 153.9 ± 46.2* / 420.9 ± 147.0 / 646.0 ± 237.9* / 572.4 ± 191.5 / 549.0 ± 152.0
Month 7.5 / 179.9 ± 49.4* / 406.7 ± 163.7 / 607.2 ± 190.0* / 527.6 ± 260.8 / 509.1 ± 134.6
Month 12 / 129.8 ± 39.3* / 284.6 ± 135.3 / 441.3 ± 171.3* / 365.8 ± 154.7 / 415.0 ± 170.0
Month 16 / 165.5 ± 60.8* / 385.9 ± 187.6 / 482.2 ± 204.5 / 472.2 ± 168.1 / 519.8 ± 188.1
Serum Bone-Specific Alkaline Phosphatase (BSAP, U/L)
Pre-surgery / 91.61 ± 26.12 / 90.55 ± 31.78 / 101.34 ± 30.24 / 101.96 ± 35.93 / 91.75 ± 33.22
Month 0 / 96.35 ± 25.28* / 207.67 ± 66.14 / 198.42 ± 44.14 / 203.59 ± 71.71 / 200.26 ± 58.12
Month 3 / 70.62 ± 17.54* / 148.31 ± 40.18 / 169.69 ± 38.24 / 167.74 ± 56.65 / 164.10 ± 54.36
Month 7.5 / 96.13 ± 24.09* / 184.70 ± 62.21 / 193.44 ± 48.15 / 185.40 ± 69.70 / 200.47 ± 54.36
Month 12 / 85.74 ± 23.59* / 157.84 ± 50.93 / 193.01 ± 50.76 / 181.20 ± 74.03 / 179.09 ± 54.02
Month 16 / 99.30 ± 27.29* / 175.75 ± 54.49 / 196.16 ± 57.94 / 200.50 ± 54.57 / 201.04 ± 66.45
Serum C-Telopeptides (CTX, ng/mL)
Pre-surgery / 1.48 ± 0.70 / 1.41 ± 0.43 / 1.51 ± 0.62 / 1.41 ± 0.59 / 1.53 ± 0.60
Month 0 / 1.10 ± 0.39* / 2.65 ± 0.62 / 2.83 ± 0.97 / 2.85 ± 0.91 / 2.93 ± 0.65
Month 3 / 0.98 ± 0.34* / 2.33 ± 0.68 / 2.59 ± 0.74 / 2.93 ± 1.42 / 2.30 ± 0.50
Month 7.5 / 1.05 ± 0.39* / 1.94 ± 0.70 / 2.13 ± 0.66 / 2.00 ± 0.62 / 1.71 ± 0.46
Month 12 / 0.97 ± 0.27* / 1.68 ± 0.70 / 2.04 ± 0.71 / 1.93 ± 0.57 / 1.98 ± 0.60
Month 16 / 1.29 ± 0.50* / 2.15 ± 0.87 / 2.04 ± 0.80 / 2.13 ± 0.61 / 2.23 ± 0.69
Urine N-Telopeptide (uNTX, nM/mM creatinine)
Pre-surgery / 122.77 ± 62.12 / 113.93 ± 45.09 / 137.94 ± 53.42 / 130.17 ± 41.65 / 154.09 ± 72.78
Month 0 / 83.65 ± 28.80* / 207.28 ± 75.36 / 213.39 ± 77.74 / 239.43 ± 90.83 / 205.00 ± 60.32
Month 3 / 92.09 ± 34.11* / 182.48 ± 68.14 / 226.05 ± 78.00 / 247.94 ± 96.02 / 198.27 ± 65.10
Month 7.5 / 98.71 ± 33.60* / 189.72 ± 53.73 / 213.86 ± 63.78 / 213.62 ± 72.96 / 177.35 ± 40.44
Month 12 / 82.36 ± 30.66* / 143.40 ± 45.94 / 188.45 ± 78.43 / 185.95 ± 89.23 / 223.91 ± 172.45
Month 16 / 108.65 ± 37.80* / 162.63 ± 51.83 / 213.89 ± 79.02 / 269.05 ± 231.9 / 197.79 ± 92.38
*P<0.05 vs Veh control; ABL, abaloparatide.
Supplemental Table S5: Additional trabecular histomorphometry for the L2 vertebral body after 16 months of treatment. Data represent means ± SD. Other L2 histomorphometry data are in Fig. 2.
Sham
(n = 14) / Veh
(n = 16) / ABL
0.2 μg/kg/d
(n = 15) / ABL
1μg/kg/d
(n = 16) / ABL
5 μg/kg/d
(n = 16)
BV/TV (%) / 34.8 ± 5.96 / 30.6 ± 6.41 / 30.9 ± 8.05 / 35.4 ± 6.99 / 34.8 ± 6.29
Tb.Th (µm) / 140 ± 29.1 / 134 ± 27.3 / 140 ± 33.7 / 148 ± 27.7 / 142 ± 24.5
Tb.Sp (µm) / 265 ± 53.4 / 306 ± 51.2 / 319 ± 69.1 / 275 ± 60.2 / 271 ± 57.9
Tb.N (mm-1) / 2.54 ± 0.42 / 2.30 ± 0.28 / 2.22 ± 0.33 / 2.40 ± 0.31 / 2.48 ± 0.41
O.Th (µm) / 10.5 ± 1.72 / 11.0 ± 1.90 / 9.8 ± 1.30 / 10.8 ± 20.6 / 10.6 ± 2.21
OS/BS (%) / 14.2 ± 5.54 / 20.9 ± 8.83 / 23.5 ± 6.92 / 18.8 ± 7.78 / 21.0 ± 9.18
OV/TV (%) / 1.69 ± 0.90 / 2.51 ± 1.38 / 2.72 ± 1.10 / 2.01 ± 1.14 / 2.40 ± 1.33
Ob.S/BS (%) / 4.7 ± 3.15* / 9.7 ± 4.47 / 10.2 ± 3.40 / 8.8 ± 4.85 / 10.1 ± 5.37
sLS/BS (%) / 14.6 ± 6.19 / 17.0 ± 5.73 / 16.2 ± 4.71 / 13.7 ± 4.92 / 17.8 ± 5.44
dLS/BS (%) / 6.0 ± 3.22* / 11.5 ± 5.29 / 11.4 ± 4.77 / 9.6 ± 5.24 / 11.5 ± 3.46
MS/BS (%) / 13.3 ± 5.30* / 20.0 ± 7.52 / 19.5 ± 6.60 / 16.4 ± 7.43 / 20.4 ± 5.95
MAR (µm/d) / 0.78 ± 0.09 / 0.78 ± 0.17 / 0.84 ± 0.10 / 0.79 ± 0.11 / 0.78 ± 0.07
Aj.AR (µm/d) / 0.67 ± 0.14 / 0.70 ± 0.21 / 0.68 ± 0.16 / 0.67 ± 0.13 / 0.71 ± 0.11
BFR/BS (µm3/µm2/d) / 38.2 ± 15.30 / 59.3 ± 30.06 / 59.9 ± 22.39 / 48.2 ± 26.36 / 58.4 ± 18.47
Ac.f (yr-1) / 1.51 ± 0.60 / 2.01 ± 1.18 / 1.57 ± 0.53 / 1.34 ± 0.72 / 1.49 ± 0.54
Rs.P (d) / 3.5 ± 4.58 / 2.1 ± 1.07 / 3.0 ± 1.63 / 3.1 ± 1.56 / 3.1 ± 1.83
Omt (d) / 13.6 ± 2.15 / 14.4 ± 2.55 / 11.8 ± 1.73* / 13.7 ± 2.49 / 13.5 ± 2.32
Mlt (d) / 16.0 ± 3.13 / 16.9 ± 5.73 / 14.9 ± 3.17 / 16.8 ± 5.74 / 15.4 ± 4.54
*P < 0.05 vs Veh group. ABL, abaloparatide; BV, bone volume; TV, total volume; Tb, trabecular; Th, thickness; Sp, spacing; N, number; O, osteoid; OS, osteoid surface; OV, osteoid volume; Ob, osteoblast; S, surface; sLS, single-labeled surface; dLS, double-labeled surface; MS, mineralizing surface; MA, mineral apposition rate; Aj.AR, adjusted apposition rate; BFR, bone formation rate; Ac.F, activation frequency; Rs.P, resorption period; Omt, osteoid maturation time; Mlt, mineralization lag time.
Supplemental Table S6: Trabecular histomorphometry for the femoral neck after 16 months of treatment. Data represent means ± SD.
histomorphometry DATA for the femoral neckSham
(n = 14) / Veh
(n = 16) / ABL
0.2 μg/kg/d
(n = 15) / ABL
1 μg/kg/d
(n = 16) / ABL
5 μg/kg/d
(n = 16)
BV/TV (%) / 29.8 ± 10.97 / 30.0 ± 8.86 / 32.1 ± 9.15 / 36.5 ± 9.09 / 37.2 ± 9.05
Tb.Th (µm) / 199 ± 42.7 / 224 ± 62.3 / 228 ± 45.0 / 253 ± 45.1 / 246 ± 51.0
Tb.Sp (µm) / 566 ± 338.9 / 535 ± 114.9 / 520 ± 192.5 / 472 ± 178.0 / 439 ± 159.3
Tb.N (mm-1) / 1.50 ± 0.53 / 1.34 ± 0.17 / 1.40 ± 0.30 / 1.46 ± 0.47 / 1.54 ± 0.36
Oc.S/BS (%) / 0.40 ± 0.47 / 0.55 ± 0.39 / 0.69 ± 0.61 / 0.71 ± 0.71 / 0.53 ± 0.46
ES/BS (%) / 4.1 ± 2.74 / 3.8 ± 2.73 / 4.7 ± 4.25 / 5.3 ± 3.98 / 3.4 ± 2.44
O.Th (µm) / 7.5 ± 2.48 / 7.9 ± 2.85 / 8.0 ± 1.25 / 8.4 ± 1.90 / 8.6 ± 1.89
OS/BS (%) / 6.0 ± 7.01 / 16.1 ± 15.06 / 14.7 ± 12.44 / 23.3 ± 14.34 / 16.3 ± 13.24
OV/TV (%) / 0.36 ± 0.47 / 1.09 ± 1.18 / 0.90 ± 0.78 / 1.28 ± 0.78 / 0.91 ± 0.78
Ob.S/BS (%) / 3.6 ± 4.91* / 11.9 ± 11.46 / 10.9 ± 10.13 / 17.5 ± 12.46 / 12.3 ± 10.53
sLS/BS (%) / 5.9 ± 4.94 / 10.3 ± 9.51 / 11.1 ± 7.76 / 18.7 ± 6.99* / 15.7 ± 9.17
dLS/BS (%) / 3.8 ± 4.11 / 9.3 ± 9.08 / 8.1 ± 8.11 / 15.1 ± 8.23 / 9.9 ± 7.45
MS/BS (%) / 6.7 ± 6.38 / 14.4 ± 13.52 / 13.6 ± 11.69 / 24.4 ± 10.99 / 17.7 ± 11.80
MAR (µm/d) / 0.56 ± 0.16 / 0.62 ± 0.24 / 0.67 ± 0.16 / 0.68 ± 0.11 / 0.66 ± 0.13
Aj.AR (µm/d) / 0.46 ± 0.21 / 0.51 ± 0.22 / 0.56 ± 0.20 / 0.64 ± 0.11 / 0.57 ± 0.14
BFR/BS (µm3/µm2/d) / 16.2 ± 17.63 / 40.5 ± 39.76 / 36.4 ± 35.74 / 60.5 ± 27.09 / 43.4 ± 30.38
Ac.f (yr-1) / 0.54 ± 0.78 / 1.27 ± 0.13 / 1.07 ± 1.09 / 1.77 ± 0.93 / 1.07 ± 0.88
W.Th (µm) / 21.2 ± 1.95* / 29.4 ± 4.57 / 32.1 ± 4.65 / 29.3 ± 2.75 / 32.4 ± 2.14
FP (d) / 64.8 ± 53.69 / 61.5 ± 27.01 / 63.8 ± 22.31 / 47.5 ± 10.82 / 60.8 ± 20.53
Rs.P (d) / 7.5 ± 9.97 / 11.6 ± 26.02 / 4.2 ± 3.53 / 1.3 ± 1.04 / 3.8 ± 6.67
Omt (d) / 14.1 ± 5.86 / 13.8 ± 5.82 / 12.4 ± 3.47 / 12.6 ± 2.81 / 13.2 ± 2.30
Mlt (d) / 20.3 ± 12.21 / 16.8 ± 12.08 / 15.9 ± 6.05 / 13.4 ± 3.17 / 15.8 ± 5.99
*P < 0.05 vs Veh group. ABL, abaloparatide; BV, bone volume; TV, total volume; Tb, trabecular; Th, thickness; Sp, spacing; Oc, osteoclast; S, surface; O, osteoid; OS, osteoid surface; OV, osteoid volume; sLS, single-labeled surface; dLS, double-labeled surface; MS, mineralizing surface; MA, mineral apposition rate; Aj.AR, adjusted apposition rate; BFR, bone formation rate; Ac.F, activation frequency; W.Th, wall thickness; FP, formation period; Rs.P, resorption period; Omt, osteoid maturation time; Mlt, mineralization lag time.
Supplemental Table S7: Cortical histomorphometry for the femoral mid-diaphysis after 16 months of treatment. Data represent means ± SD. Other femoral diaphysis histomorphometry data are in Fig. 2.
ADDITIONAL histomorphometry data forthe femoral diaphysis
Sham
(n = 14) / Veh
(n = 16) / ABL
0.2 μg/kg/d
(n = 15) / ABL
1 μg/kg/d
(n = 16) / ABL
5 μg/kg/d
(n = 16)
Tt.T.Ar (mm2) / 68.87 ± 8.49 / 68.28 ± 8.57 / 66.72 ± 4.83 / 67.82 ± 7.96 / 68.09 ± 7.04
Ct.Ar (mm2) / 46.75 ± 4.32 / 45.73 ± 5.08 / 45.58 ± 4.37 / 46.28 ± 3.45 / 45.93 ± 3.25
Me.Ar (mm2) / 22.11 ± 6.39 / 22.55 ± 4.91 / 21.14 ± 4.63 / 21.54 ± 5.92 / 22.16 ± 4.80
Ct.Wi (mm) / 2.04 ± 0.21 / 1.96 ± 0.16 / 1.99 ± 0.22 / 2.03 ± 0.15 / 1.99 ± 0.12
Ps.Pm (mm) / 30.18 ± 1.88 / 30.03 ± 1.87 / 29.78 ± 1.04 / 29.94 ± 1.70 / 30.09 ± 1.57
Ec.Pm (mm) / 17.32 ± 2.66 / 17.47 ± 1.96 / 16.88 ± 1.74 / 17.05 ± 2.30 / 17.32 ± 1.87
H.W.Th (µm) / 65 ± 4.7 / 68 ± 8.8 / 70 ± 6.8 / 69 ± 6.3 / 72 ± 8.4
Ps.sL.Pm/Ps.Pm (%) / 2.7 ± 5.20 / 6.9 ± 10.11 / 7.5 ± 8.46 / 12.1 ± 9.58 / 12.6 ± 11.09
Ps.dL.Pm/Ps.Pm (%) / 0.8 ± 1.59 / 1.4 ± 2.94 / 2.3 ± 3.70 / 3.3 ± 4.83 / 5.1 ± 8.35
Ps.L.Pm/Ps.Pm (%) / 2.2 ± 3.95 / 4.9 ± 7.68 / 6.0 ± 7.47 / 9.3 ± 9.05 / 11.4 ± 13.66
Ps.MAR (µm/d) / 0.36 ± 0.23 / 0.35 ± 0.21 / 0.40 ± 0.25 / 0.50 ± 0.19 / 0.47 ± 0.19
Ps.BFR/BS (µm3/µm2/yr) / 4.8 ± 8.90 / 10.8 ± 20.33 / 13.2 ± 18.97 / 20.1 ± 22.17 / 24.0 ± 32.81
Ec.sL.Pm/Ec.Pm (%) / 3.9 ± 7.52 / 13.0 ± 9.04 / 10.3 ± 9.68 / 18.6 ± 11.56 / 22.2 ± 12.97*
Ec.dL.Pm/Ec.Pm (%) / 2.2 ± 3.54 / 5.5 ± 5.48 / 5.4 ± 7.10 / 12.7 ± 16.67 / 11.3 ± 7.89
Ec.MAR (µm/d) / 0.35 ± 0.22 / 0.54 ± 0.20 / 0.53 ± 0.23 / 0.54 ± 0.14 / 0.64 ± 0.08
H.L.Pm/H.Pm (%) / 2.2 ± 2.67* / 9.7 ± 4.22 / 10.1 ± 3.85 / 9.7 ± 5.83 / 11.8 ± 7.19
H.MAR (µm/d) / 0.57 ± 0.28* / 0.94 ± 0.14 / 0.93 ± 0.11 / 0.94 ± 0.14 / 0.95 ± 0.14
H.BFR/BS (µm3/µm2/yr) / 6.2 ± 8.42* / 32.5 ± 13.55 / 34.4 ± 14.68 / 32.8 ± 18.07 / 40.8 ± 25.32
*P < 0.05 vs Veh group. ABL, abaloparatide; Tt, total; T, tissue; Ar, area; Ct, cortical; Me, medullary; Wi, width; Ps, periosteal; Ec, endocortical; Pm, perimeter; H, Haversian; W, wall; Th, thickness; sL, single-labeled; dL, double-labeled; L, labeled; MAR, mineral apposition rate; BFR, bone formation rate; BS, bone surface.
Supplemental Table S8: pQCT and micro-CT data for cortical volumetric BMD (vBMD) at various skeletal sites after 16 months of treatment. Data represent means ± SD. *P < 0.05 vs Veh group.
Cortical vBmd (mg/cm3)Sham
n = 14 / Veh
n = 16 / ABL
0.2 μg/kg/d
n = 15 / ABL
1 μg/kg/d
n = 16 / ABL
5 μg/kg/d
n = 16
Tibial diaphysis (in vivo pQCT, month 16) / 1056.5
± 18.5 / 1019.5
± 30.8 / 1026.7
± 29.1 / 1036.7
± 15.2 / 1035.6
± 27.5
Radius diaphysis
(in vivo pQCT, month 16) / 1151.5
± 23.8 / 1116.3
± 39.9 / 1123.4
± 32.6 / 1129.5
± 16.8 / 1125.3
± 26.2
Femoral diaphysis (ex vivo pQCT) / 1301.7*
± 23.6 / 1276.7
± 29.0 / 1267.3
± 26.9 / 1274.9
± 14.4 / 1271.7
± 24.0
Distal femoral metaphyseal cortex
(ex vivo micro-CT) / 1017.4*
± 17.0 / 976.2
± 28.8 / 979.7
± 21.7 / 978.0
± 15.0 / 979.1
± 27.4
T12 cortical shell
(ex vivo micro-CT) / 873.5*
± 25.0 / 829.6
± 28.0 / 832.8
± 34.8 / 829.5
± 29.5 / 821.2
± 40.5
Humeral cortical beam
(ex vivo micro-CT) / 1172.9
± 39.5 / 1128.2
± 55.9 / 1123.4
± 57.8 / 1132.2
± 42.0 / 1130.9
± 52.0
*P < 0.05 vs Veh group. pQCT, peripheral quantitative computed tomography; Micro-CT, micro-computed tomography; vBMD, volumetric bone mineral density; Veh, vehicle, ABL, abaloparatide.
Supplemental Table S9: Destructive biomechanical testing data for the femoral diaphysis 3-point bending test after 16 months of treatment. Data represent means ± SD.
Sham
n = 14 / Veh
n = 16 / ABL
0.2 μg/kg/d
n = 14-15 / ABL
1 μg/kg/d
n = 16 / ABL
5μg/kg/d
n = 16
Peak Load
(N) / 1345.7
± 174.8 / 1316.3
± 205.3 / 1295.4
± 194.1 / 1328.0
± 157.6 / 1272.8
± 146.7
Stiffness
(N/mm) / 1120
± 143.5 / 1036
± 174.7 / 1029
± 121.9 / 1072
± 129.7 / 1038
± 163.4
Energy (AUC)
(N-mm) / 3169
± 896.8 / 3335
± 714.1 / 3453
± 586.9 / 3707
± 880.1 / 3720
± 773.9
Ultimate Stress
(MPa) / 223.15
± 24.66 / 223.57
± 25.4 / 225.43
± 22.46 / 229.16
± 20.73 / 226.70
± 16.30
Modulus
(MPa) / 8964
± 1730.9 / 8494
± 1927.4 / 8644
± 1080.6 / 8776
± 1158.0 / 8898
± 953.4
Toughness
(MPa) / 10.93
± 2.67 / 11.94
± 1.99 / 12.57
± 1.81 / 13.49
± 2.76 / 13.75
± 2.62
Displacement at Yield
(mm) / 1.07
± 0.20 / 0.96
± 0.19 / 0.97
± 0.17 / 0.92
± 0.129 / 0.94
± 0.16
Post-yield displacement
(mm) / 2.23
± 0.58 / 2.47
± 0.48 / 2.56
± 0.45 / 2.74
± 0.53 / 2.94
± 0.90
Post-yield toughness
(MPa) / 9.43
± 2.62 / 10.48
± 1.93 / 11.02
± 1.91 / 12.05
± 2.72 / 12.33
± 2.80
Veh, vehicle; ABL, abaloparatide; N, newtons; AUC, area under the curve; MPa, megapascals.
Supplemental Table S10: Destructive biomechanical testing data for the femoral neck shear test after 16 months of treatment. Data represent means ± SD.
Femoral NECK SHEAR TEST DataSham
n = 14 / Veh
n = 16 / ABL
0.2 μg/kg/d
n = 15 / ABL
1 μg/kg/d
n = 16 / ABL
5 μg/kg/d
n = 16
Peak Load
(N) / 1671.5
± 296.6 / 1600.6
± 266.6 / 1520.2
± 298.5 / 1701.4
± 259.9 / 1701.1
± 294.1
Stiffness
(N/mm) / 1686
± 264.4 / 1603
± 144.9 / 1553
± 298.5 / 1621
± 219.4 / 1698
± 205.3
Energy (AUC)
(N-mm) / 2291
± 1103.3 / 2722
± 1415.3 / 1922
± 685.7 / 2539
± 829.6 / 2701
± 1316.4
Ultimate Displacement
(mm) / 2.08
± 0.57 / 2.45
± 0.83 / 1.93
± 0.40 / 2.34
± 0.72 / 2.29
± 0.68
V, vehicle; ABL, abaloparatide; N, newtons; AUC, area under the curve.
Supplemental Table S11: Destructive biomechanical testing data for the humeral cortical beam 3-point bending test. Data represent means ± SD.
humeral cortical beam 3-point bending Test DataSham
n = 14 / Veh
n = 15-16 / ABL
0.2 μg/kg/d
n = 15 / ABL
1 μg/kg/d
n = 16 / ABL
5 μg/kg/d
n = 16
Peak Load
(N) / 21.2
± 1.36 / 20.6
± 1.98 / 20.8
± 1.86 / 20.5
± 2.13 / 20.6
± 1.58
Stiffness
(N/mm) / 19.1
± 1.67 / 17.7
± 3.02 / 17.4
± 2.23 / 17.6
± 2.58 / 17.9
± 1.63
Energy (AUC)
(N-mm) / 40.29
± 14.72 / 45.13
± 13.43 / 48.96
± 10.73 / 45.99
± 11.42 / 46.45
± 12.56
Ultimate Stress
(MPa) / 254.01
± 18.14 / 246.65
± 21.99 / 252.07
± 21.18 / 245.54
± 25.11 / 250.16
± 15.64
Modulus
(MPa) / 23690
± 2084 / 21895
± 3628 / 27183
± 2791 / 21805
± 3198 / 22470
± 1794
Toughness
(MPa) / 4.69
± 1.74 / 5.24
± 1.56 / 5.75
± 1.27 / 5.36
± 1.34 / 5.46
± 1.45
Displacement at Yield
(mm) / 1.02
± 0.06 / 1.03
± 0.06 / 1.05
± 0.07 / 1.02
± 0.07 / 1.03
± 0.04
Post-yield displacement
(mm) / 1.69
± 1.12 / 1.90
± 0.85 / 2.06
± 0.76 / 1.93
± 0.66 / 1.90
± 0.61
Post-yield toughness
(MPa) / 3.40
± 1.70 / 4.04
± 1.56 / 4.49
± 1.35 / 4.15
± 1.36 / 4.20
± 1.44
Veh, vehicle; ABL, abaloparatide; AUC, area under the curve; N, newtons; MPa, megapascals.
Supplemental Table S12: Additional destructive biomechanical testing data for the L3-L4 vertebral body compression test. Data represent means ± SD of L3 and L4 values averaged together for each animal. Other L3-L4 biomechanics data are in Fig. 6.
additional L3-L4 Vertebral compression Test DataSham
n = 14 / Veh
n = 15-16 / ABL
0.2 μg/kg/d
n = 15 / ABL
1 μg/kg/d
n = 16 / ABL
5 μg/kg/d
n = 16
Energy (AUC)
(N-mm) / 2403*
± 1378.5 / 1215
± 922.6 / 1351
± 787.8 / 1917
± 1181.3 / 2165
± 1543.3
Displacement at Yield
(mm) / 0.30
± 0.06 / 0.28
± 0.05 / 0.27
± 0.04 / 0.29
± 0.05 / 0.29
± 0.06
Post-yield displacement
(mm) / 0.57
± 0.34 / 0.33
± 0.26 / 0.39
± 0.24 / 0.45
± 0.27 / 0.53
± 0.36
Post-yield toughness
(MPa) / 2.39
± 1.79 / 1.05
± 1.00 / 1.24
± 0.90 / 1.77
± 1.39 / 2.07
± 1.64
*P < 0.05 vs Veh group. Veh, vehicle; ABL, abaloparatide;AUC, area under the curve; MPa, megapascals.
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