Table 1.
Concentrations and performance of the panel of soluble biomarkers analysed for the FNIH OA Biomarkers Consortium project
| Biomarkers (units) | Comparators Baseline mean (SD) Median (range) (n=406) |
Cases Baseline mean (SD) Median (range) (n=194) |
CV (%) |
Number of samples below LLOQ (out of n=1785) |
Biological process indicated | Manufacturer (catalogue #) |
|---|---|---|---|---|---|---|
| Serum C1, 2C (µg/mL) | 0.38 (0.14) | 0.39 (0.15) | 23.3 | 3 | Types I and II collagen degradation | IBEX (60-1002-001) |
| 0.37 (0.04–1.34) | 0.38 (0.05–1.09) | |||||
|
| ||||||
| Serum-C2C (ng/ml) | 208.9 (46.8) | 212.0 (54.9) | 11.7 | 0 | Type II collagen degradation | IBEX (60-1001-001) |
| 202.0 (100.0–395.0) | 204.0 (102.0–423.0) | |||||
|
| ||||||
| Serum Coll2-1 NO2 (nM) | 8.93 (5.45) | 8.91 (4.99) | 13.6 | 19 | Type II collagen degradation and inflammation | Artialis (ACP022) |
| 7.97 (0.00–45.17) | 8.20 (0.00–37.98) | |||||
|
| ||||||
| Serum CPII (ng/mL) | 945.7 (391.0) | 944.2 (363.2) | 12.2 | 0 | Type II collagen synthesis | IBEX (60-1003-001) |
| 889.0 (252.0–4063.0) | 894.0 (204.0–3006.0) | |||||
|
| ||||||
| Serum CS846 (ng/mL) | 76.8 (52.8) | 79.2 (60.2) | 16.8 | 1354 | Cartilage aggrecan synthesis/turnover | IBEX (60-1004) |
| 66.0 (1.0–383.0) | 65.0 (0.0–412.0) | |||||
|
| ||||||
| Serum CTX1 (ng/mL) | 0.39 (0.22) | 0.42 (0.21) | 4.9 | 123 | Bone resorption | IDS (AC-02F1) |
| 0.34 (0.08–1.79) | 0.39 (0.07–1.23) | |||||
|
| ||||||
| Serum COMP (ng/mL) | 783.4 (302.5) | 761.1 (280.1) | 5.2 | 5 | Cartilage degradation | BioVendor (RD194080200) |
| 739.0 (156.0–2007.0) | 705.0 (168.0–1903.0) | |||||
|
| ||||||
| Serum HA (ng/mL) | 45.2 (40.2) | 49.5 (36.5) | 7.4 | 1170 | Osteophyte burden, synovitis | Corgenix (029-001) |
| 34.0 (3.0–297.0) | 38.0 (4.0–193.0) | |||||
|
| ||||||
| Serum MMP3 (ng/mL) | 16.9 (11.2) | 17.5 (11.3) | 9.6 | 27 | Total (active and inactive) metalloprotease involved with joint tissue degradation | Invitrogen (Life Technologies) (KAC1541) |
| 14.6 (0.0–99.9) | 14.4 (1.0–76.3) | |||||
|
| ||||||
| Serum NTXI (nm BCE) | 14.8 (4.8) | 15.5 (4.9) | 7.01 | 8 | Bone resorption | ALERE -Osteomark (Inverness Medical) (9021) |
| 14.0 (3.0–43.0) | 15.0 (4.0–28.0) | |||||
|
| ||||||
| Serum PIIANP (ng/mL) | 2677.2 (752.5) | 2581.1 (783.7) | 12.3 | 0 | Type II collagen synthesis | Merck Group/Millipore (EZPIIANP-53K) |
| 2626.5 (160.0–5656.0) | 2524.0 (781.0–5219.0) | |||||
|
| ||||||
| Urine Col2-1 NO2 (nM/mmol Cr) | 0.024 (0.015) | 0.025 (0.014) | 9.3 | 659 | Type II collagen degradation and inflammation | Artialis (ACP021) |
| 0.020 (0.003–0.108) | 0.021 (0.002–0.120) | |||||
|
| ||||||
| Urine C1, 2C (ng/mmol Cr) | 0.011 (0.011) | 0.010 (0.011) | 21.5 | 805 | Types I and II collagen degradation | IBEX (60-1002-001) |
| 0.009 (0.000–0.063) | 0.007 (0.000–0.045) | |||||
|
| ||||||
| Urine C2C-HUSA (ng/mmol Cr) | 152.7 (90.3) | 165.6 (103.0) | 6.24 | 104 | Type II collagen degradation | IBEX (60-1017) |
| 137.9 (0.0–763.3) | 149.1 (0.0–695.1) | |||||
|
| ||||||
| Urine CTXII (ng/mmol Cr) | 287.7 (190.7) | 333.1 (210.5) | 5.21 | 271 | Type II collagen degradation | IDS (AC-10F1) |
| 233.5 (0.0–1794.1) | 283.7 (59.4–1446.4) | |||||
|
| ||||||
| Urine NTXI (nM BCE/mmol Cr) | 32.6 (18.2) | 34.9 (16.6) | 3.03 | 16 | Bone resorption | ALERE -Osteomark (Inverness Medical) (9006) |
| 29.1 (6.2–152.0) | 32.1 (8.6–116.4) | |||||
|
| ||||||
| Urine CTXIα (µg/mmol Cr) | 0.41 (0.33) | 0.46 (0.33) | 3.91 | 961 | Turnover of newly formed bone | IDS (AC-04F1) |
| 0.34 (0.00–2.76) | 0.39 (0.00–2.56) | |||||
|
| ||||||
| Urine CTX1 β (µg/mmol Cr) | 2.19 (1.67) | 2.34 (1.61) | 7.67 | 465 | bone resorption | IDS (AC-05F1) |
| 1.79 (0.00–11.08) | 2.04 (0.00–7.98) | |||||
|
| ||||||
| Urine creatinine (mmol/L) | 7.32 (5.23) | 6.94 (5.20) | 3.02 | 0 | Normalization analyte for urinary biomarkers | Quidel MicroVue (8009) |
| 6.00 (0.30–33.90) | 5.50 (0.40–25.50) | |||||
Urine biomarkers are normalised to urinary creatinine.
BCE, bone collagen equivalents; COMP, cartilage oligomeric matrix protein; CPII, C-propeptide of type II collagen; Cr, creatinine; CS846, chondroitin sulfate 846 epitope; CTXI, C-terminal crosslinked telopeptide of type I collagen; CTXII, C-terminal crosslinked telopeptide type II collagen; CV, interassay coefficient of variation; FNIH, Foundations for National Institutes of Health; HA, hyaluronan; LLOQ, lower limit of quantification; NTXI, N-telopeptide of type I collagen; OA, osteoarthritis.