Table 2.
Outcome Measures Used in the Included Studies a
| Outcome | Biomarkers Investigated and Associated With Outcome During at Least 1 Time Point | Biomarkers Investigated and Not Associated With Outcome |
|---|---|---|
| Patient-Reported Outcome Measures | ||
| VAS pain or NPRS | sf-IL-6, sf-CTX-II (Sullivan et al
60
) u-CTX-II (Chmielewski et al 7 ) sf-IL-6, sf-IL-1 (Gupta et al 19 ) |
sf-IL-6, sf-IL-1Ra, sf-MIP-B, sf-MCP-1, sf-RATNES, sf-VEGF, sf-bFGF, sf-MMP-3, sf-TIMP-1, sf-TIMP2 (Markus et al
44
) sf IL-1β (Sullivan et al 60 ) sf-TNF-α (Gupta et al 19 ) |
| Lysholm score | sf-IL-6 (Gupta et al 19 ) | sf-IL-6, sf-IL-1Ra, sf-MIP-B, sf-MCP-1, sf-RATNES, sf-VEGF, sf-bFGF, sf-MMP-3, sf-TIMP-1, sf-TIMP2 (Markus et al
44
) sf-IL-1, sf-TNF-α (Gupta et al 19 ) |
| KOOS/KOOS-QOL | sf-IL-1α, sf-IL-1Ra, sf-MMP-9 (Lattermann et al 36 ) | sf-IL-6, sf-IL-1Ra, sf-MIP-B, sf-MCP-1, sf-RATNES, sf-VEGF, sf-bFGF, sf-MMP-3, sf-TIMP-1, sf-TIMP2 (Markus et al
44
) sf-COMP, sf-CTX-II, u-CTX-II, sGAG, sf-IL-1β, sf-MMP-1, sf-MMP-3, sf-NTX-I, sf-TSG-6 (Lattermann et al 36 ) s-MCP-1/s-COMP biochemical profile (Lisee et al 40 ) |
| Tegner activity scale | sf-IL-6 (Gupta et al 19 ) | sf-IL-6, sf-IL-1Ra, sf-MIP-B, sf-MCP-1, sf-RATNES, sf-VEGF, sf-bFGF, sf-MMP-3, sf-TIMP-1, sf-TIMP2 (Markus et al
44
) sf-IL-1, sf-TNF-α (Gupta et al 19 ) |
| IKDC/IKDC-SKF | u-CTX-II (Chmielewski et al
7
) sf-IL-1α (Lattermann et al 36 ) |
sf-COMP, sf-CTX-II, u-CTX-II, sGAG, sf-IL-1β, sf-IL-1Ra, sf-MMP-1, sf-MMP-3, sf-MMP-9, sf-NTX-I, sf-TSG-6 (Lattermann et al 36 ) |
| Marx activity scale | — | s-MCP-1/s-COMP biochemical profile (Lisee et al 40 ) |
| Imaging-Based Outcome Measures | ||
| Osteoarthritis (modified Outerbridge assessment per Colak et al 10 on 3-T MRI) | sf-MCP-1, sf-VEGF, sf-IL-1Ra (Markus et al 44 ) | sf-IL-6, sf-MIP-B, sf-RATNES, sf-bFGF, sf-MMP-3, sf-TIMP-1, sf-TIMP2 (Markus et al 44 ) |
| Osteoarthritis (joint-space width on weightbearing radiograph per Dupuis et al 13 ) | — | u-C2C/s-CP-II ratio (Tourville et al 63 ) |
| Osteoarthritis (T1ρ and T2 quantitative assessment per Li et al37,38 on 3-T MRI) | High sf-GAG/low sf-IL-6; IL-8; IL-10; TNF-α; MMP-1; MMP-3 biochemical profile (Amano et al 3 ) | High sf-IL-6; IL-8; IL-10; TNF-α; MMP-1; MMP-3/low sf-GAG biochemical profile (Amano et al 3 ) |
| Osteoarthritis (MRI T1ρ relaxation times) | High s-MCP-1/s-COMP biochemical profile (Lisee et al 40 ) | — |
| Tunnel enlargement (measured on plain radiograph) | sf-IL-6, sf-TNF-α, sf-NO (Zysk et al 69 ) | sf-IL-1β, sf-BMP-2 (Zysk et al 69 ) |
| Other Outcome Measures | ||
| Arthrofibrosis (requiring manipulation or arthrolysis) | sf-RANTES, sf-bFGF (Avila et al 4 ) | sf-IL-6, sf-VEGF-A, sf-TIMP-1, sf-IL-1Ra, sf-MMP-3, sf-MCP-1, sf-MIP-1B (Avila et al 4 ) |
| Gait biomechanics (vertical ground-reaction force, knee flexion angle, internal knee extension moment) | sf-MMP-3, sf-IL-6 (Evans-Pickett et al 15 ) | — |
| ACL laxity (KT-1000 arthrometer) | sf-IL-6 (Gupta et al 19 ) | sf-IL-1, sf-TNF-α (Gupta et al 19 ) |
| Physical Activity Score | sf-IL-1β (Inoue et al 25 ) | sf-TNF-α, sf-IL-2, sf-IL-6, sf-IL-8, sf-IL-10, sf-IFN-γ (Inoue et al 25 ) |
| Cyclops lesion | TTT (IgM) (Kodama et al 32 ) | |
| Walking speed | s-C2C (Pietrosimone et al 54 ) | s-Aggrecan (Pietrosimone et al 54 ) |
| Gait biomechanics (peak vertical ground-reaction force, vertical ground-reaction loading rate, knee adduction moment) | s-IL-6, s-MMP-3, s-C2C/CPII (Pietrosimone et al 53 ) | — |
| Osteoarthritis (arthroscopic chondral assessment) | sf-Δdi-C6S, sf-KS, sf-C6s/C4S ratio (Sobue et al 56 ) | sf-C2C, sf-Δdi-C4S, sf-C2C/KS ratio (Sobue et al 56 ) |
a
See Appendix Table A2 for a list of biomarker abbreviations. Biomarker prefixes: s-, serum; sf-, synovial fluid; u-, urinary. ACL, anterior cruciate ligament; IKDC, International Knee Documentation Committee; KOOS, Knee injury and Osteoarthritis Outcome Score; MRI, magnetic resonance imaging; NPRS, numeric pain rating scale; QOL, Quality of Life; SKF, Subjective Knee Evaluation Form; VAS, visual analog scale.