Group rating (0–10 numerical rating scale) of the strength of evidence (SOE) in support of each biomarker as reflecting structural damage according to individual validation criteria.
| Criterion | RANKL (SOE) mean (SD) | OPG (SOE) mean (SD) | CTX-I (SOE) mean (SD) | CTX-II (SOE) mean (SD) | MMP 3 (SOE) mean (SD) |
|---|---|---|---|---|---|
| Truth | |||||
| 1. (Data from animal models) | 2.3 (1.9) | 1.4 (1.3) | 2.3 (1.9) | 2.3 (1.9) | 0.3 (0.8) |
| 2. (Localization to joints) | 8.1 (1.0) | 4.9 (3.1) | 2.5 (3.3) | 2.5 (3.3) | 7.4 (2.0) |
| 3. (Sensitivity/specificity for joints) | 1.9 (2.0) | 1.8 (2.1) | 3.1 (2.5) | 3.1 (2.5) | 2.2 (2.1) |
| 4. (Known relation to joint turnover) | 6.8 (1.9) | 6.5 (1.9) | 5.2 (2.9) | 5.2 (2.9) | 6.9 (2.0) |
| 5. (Correlation with other surrogates) | 2.7 (1.6) | 2.6 (1.4) | 3.2 (1.8) | 3.2 (1.8) | 5.3 (2.1) |
| Discrimination | |||||
| 6. (Assay reproducibility) | 7.6 (2.5) | 7.8 (2.1) | 8.4 (1.7) | 8.4 (1.7) | 7.0 (1.9) |
| 7. (Effect of sources of variability) | 4.8 (1.8) | 5.8 (1.8) | 5.8 (1.5) | 5.8 (1.5) | 5.7 (1.9) |
| 8. (Known metabolism of biomarker) | 0.1 (0.3) | 0.1 (0.3) | 0.1 (0.3) | 0.1 (0.3) | 0.1 (0.3) |
| 9. (Sensitivity/specificity in disease vs controls) | 2.9 (1.7) | 2.9 (1.7) | 4.0 (1.5) | 4.0 (1.5) | 5.9 (1.5) |
| 10. (Association with damage in prospective studies) | 3.8 (2.0) | 4.2(1.8) | 4.3 (1.7) | 4.3 (1.7) | 4.7 (1.7) |
| 11. (Association with damage in RCT) | 0.3 (0.4) | 0.3 (1.4) | 1.4 (2.2) | 1.4 (2.2) | 0.2 (0.5) |
| 12. (Association with damage in pre-radiographic disease) | 0.0 (0.0) | 0.0 (0.0) | 3.9 (2.3) | 3.9 (2.3) | 0.0 (0.0) |
| Feasibility | |||||
| 13. (Well characterized assay) | 3.7 (2.2) | 3.8 (2.0) | 4.1 (2.1) | 4.1 (2.1) | 4.1 (2.1) |
| 14. (Biomarker stability) | 4.3 (2.7) | 1.7 (1.8) | 6.3 (2.8) | 6.3 (2.8) | 1.3 (1.8) |
RANKL: receptor activator of NF-κB ligand; OPG: osteoprotegerin; CTX-I: C-telopeptide of type I collagen I; CTX-II: C-telopeptide of type II collagen; MMP-3: metalloproteinase 3; RCT: randomized controlled trial.