Histopathology summary, n=10/group; mean (SE)
| Parameter/day | Isotype control | Vehicle control | Sham surgery | Tanezumab 0.1 mg/kg/week | Tanezumab 1 mg/kg/week | Tanezumab 10 mg/kg/week |
|---|---|---|---|---|---|---|
| Growth plate difference (medial-lateral), µm | ||||||
| 7 | 41.33 (5.43) | 33.33 (2.22) | 5.33 (2.95)*** | 50.67 (10.29) | 60.00 (8.94) | 70.67 (11.60) |
| 14 | 68.00 (15.83) | 50.67 (7.38) | 46.67 (5.71) | 74.67 (8.93) | 164.00 (26.15)** | 141.33 (22.59)* |
| 28 | 33.33 (4.10) | 32.00 (4.07) | 16.00 (5.55)* | 65.33 (10.60) | 185.33 (50.73)*** | 161.33 (76.24)** |
| Medial collateral ligament, µm | ||||||
| 7 | 865.33 (26.70) | 893.33 (13.91) | 870.67 (35.84) | 1068.00 (33.46)** | 1041.33 (48.42)* | 1128.00 (60.65)*** |
| 14 | 637.33 (26.28) | 633.33 (31.13) | 641.33 (28.63) | 664.00 (24.49) | 689.33 (31.74) | 688.00 (29.02) |
| 28 | 476.00 (16.03) | 466.67 (15.78) | 472.00 (20.09) | 530.67 (17.87) | 570.67 (22.82)** | 545.33 (15.71)* |
| Bone damage score† | ||||||
| 7 | 2.00 (0.15) | 2.00 (0.00) | 0.00 (0.00)*** | 2.40 (0.16) | 2.20 (0.13) | 2.20 (0.13) |
| 14 | 2.80 (0.25) | 2.60 (0.16) | 0.00 (0.00)*** | 3.10 (0.31) | 2.60 (0.16) | 2.70 (0.30) |
| 28 | 3.00 (0.26) | 3.40 (0.16) | 0.00 (0.00)*** | 4.60 (0.16)** | 4.40 (0.34)** | 4.20 (0.29)* |
| Bone sclerosis score‡ | ||||||
| 7 | 1.30 (0.15) | 1.20 (0.13) | 0.20 (0.13)*** | 2.30 (0.15)** | 2.10 (0.10)* | 2.70 (0.26)*** |
| 14 | 2.20 (0.20) | 2.50 (0.17) | 0.10 (0.10)*** | 3.50 (0.17)** | 3.70 (0.15)*** | 3.80 (0.13)*** |
| 28 | 2.80 (0.25) | 3.70 (0.26)* | 0.20 (0.13)*** | 4.60 (0.16)*** | 4.80 (0.13)*** | 4.70 (0.15)*** |
| Tibial osteophyte size, µm | ||||||
| 7 | 119.33 (26.79) | 121.33 (26.88) | 0 (0.00)*** | 167.33 (21.79) | 150.33 (29.65) | 223.67 (14.59)* |
| 14 | 309.67 (10.90) | 299.67 (16.03) | 0 (0.00)*** | 382.67 (27.93) | 476.67 (43.62)** | 417.67 (41.30) |
| 28 | 581.67 (34.20) | 601.67 (27.38) | 0 (0.00)*** | 1106.67 (49.20)*** | 1068.33 (75.30)*** | 1093.33 (50.63)*** |
*p<0.05 versus isotype control; **p<0.01 versus isotype control; ***p<0.001 versus isotype control.
†Damage to calcified cartilage and subchondral bone was scored on a 6-point numerical scale (0=no changes to 5=increased basophilia; marked to severe fragmentation of calcified cartilage, mesenchymal change in marrow involves up to three-fourths of the total area and articular cartilage has collapsed into the epiphysis to a depth of >250 µm from tidemark).
‡Medial tibial subchondral/epiphysial bone sclerosis was scored on a 6-point numerical scale (0=no changes to 5=76%–100% increase in subchondral or epiphysial trabecular bone thickness in medial versus lateral; very little marrow space remains in medial tibia).