Table 2.
Biomarkers for the diagnosis of hip OA
| Marker | Source | Study | Definition of hip OA | Hip OA cohort, number (mean age ± SD [years]; men:women) | Control cohort, number (mean age ± SD [years]; men:women) | Hip OA biomarker levels, mean (± SD) ng/mL (unless otherwise specified) | Control biomarker levels, mean (± SD) ng/mL (unless otherwise specified) | Statistical association | Effect size (Glass’ delta) |
|---|---|---|---|---|---|---|---|---|---|
| CTX-II | Urine | Garnero et al., 2003 [19]* | ACR criteria | 40 (64 ± 12; 17:23) | 65 (63 ± 8; 27:38) | 492 (± 232) ng/mmol Cr | 342 (± 141) ng/mmol Cr | Yes; OA > controls; p < 0.001 | 2.2 |
| Jung et al., 2004 [22] | XR and clinical criteria NS | 51 (61 ± 10; 31:21) | 48 (66 ± 8; 19:29) | 597 (± 499) ng/mmol | 190 (± 109) ng/mmol | Yes; OA > controls; p < 0 .001 | 3.7 | ||
| Reijman et al., 2004 [37]* | K-L grade 2–4 | 123 (70 ± 7; 51:72) | 1112 (66 ± 7; 466:646) | 231.5 (NS) ng/mmol Cr | 172.0 (NS) ng/mmol Cr | Yes; OA > controls; p < 0.001 | N/A | ||
| CRP | Serum | Conrozier et al., 2000 [11] | ACR criteria | 45 (65 ± NS; 21:24) | 33 (42 ± NS; NS) | 2930 (± 3030) | 1400 (± 1610) | Yes; OA > controls; p = 0.006 | 1.0 |
| Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 2200 (± 1600) | 2800 (± 2800)° | No; NS | −0.2 | ||
| Hulejová et al., 2007 [21] | THA for OA K-L grade 3–4 | 55 (68 ± 10; 9:46) | 30 (56 ± 11; 8:22) | 9800 (± 13000) | 1200 (± 300) | Yes; OA > controls; p < 0.001 | 28.7 | ||
| TGF-β1 | Serum | Nelson et al., 2009 [34] | K-L grade 2–4; | 68 (NS; NS) | 241 (NS; NS) | 16.4 (NS) | 16.5 (NS) | No; p = 0.713 | N/A |
| JSN NS | 80 (NS; NS) | 226 (NS; NS) | 2.8 (NS) Ln ng/mL | 2.8 (NS) Ln ng/mL | No; p = 0.857 | N/A | |||
| Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 16.7 (13.1–21.3)† | 8.6 (6.3–11.7)† | Yes; OA > controls; p = 0.014 | N/A | ||
| Helix-II | Urine | Garnero et al., 2006 [18]* | ACR criteria | 40 (64 ± 12; 17:23) | 75 (63 ± 11; 28:47) | 281 (± 131) ng/mmol Cr | 200 (± 113) ng/mmol Cr | Yes; OA > controls; p = 0.004 | 0.7 |
| DPD | Urine | Stewart et al., 1999 [43] | Hip pain; radiographic OA NS | 28 (69 ± 6; 0:30) | 26 (70 ± 6; NS) | 24.3 (± 12.7) nmol/mmol Cr | 17.3 (± 15.3) nmol/mmol Cr | Yes; OA > OP and controls; p = 0.001; Yes; PYD:DPD ratio | 0.5 |
| Garnero et al., 2003 [19]* | ACR criteria | 40 (64 ± 12; 17:23) | 65 (63 ± 8; 27:38) | 3.2 (± 1.3) nmol/mmol Cr | 3.5 (± 0.9) nmol/mmol Cr | No; p = 0.3 | −0.3 | ||
| PYD | Urine | Stewart et al., 1999 [43] | Hip pain; radiographic OA NS | 30 (69 ± 6; 0:30) | 30 (70 ± 6; NS) | 90.8 (± 30.6) nmol/mmol Cr | 59.3 (± 15.1) nmol/mmol Cr | Yes; OA > OP and controls; p < 0.001; yes; PYD:DPD ratio | 2.1 |
| MMP-3 | Serum | Hulejová et al., 2007 [21] | THA for OA K-L grade 3–4 | 55 (68 ± 10; 9:46) | 30 (56 ± 11; 8:22) | 91.6 (± 20.3) pg/mL | 26.4 (± 10.5) pg/mL | Yes; OA > Controls; p = 0.03 |
6.2 |
| YKL-40 | Serum | Conrozier et al., 2000 [11] | ACR criteria | 45 (65 ± NS; 21:24) | 33 (42 ± NS; NS) | 90.3 (± 8.2) | 66.9 (± 8.2) | Yes; OA > controls; p = 0.035 |
2.0 |
| AAT | Serum | Olszewska-Slonina et al., 2013 [36] | Clinical diagnosis, K-L grade 3–4 | 46 (NS; 15:31) | 54 (63 ± 14; 26:28) | 0.9 (± 0.3) mg inhibited trypsin/mL blood serum | 0.7 (± 0.4) mg inhibited trypsin/mL blood serum | Yes; OA > control; p = 0.003 | 0.5 |
| CAT-D | Serum | Olszewska-Slonina et al., 2013 [36] | Clinical history, K-L grade 3–4 | 46 (NS; 15:31) | 54 (63 ± 14; 26:28) | 11.1 (± 4.8) nM released tyrosine/mg protein/min |
23.7 (± 13.1) nM released tyrosine/mg protein/min |
Yes; OA < controls; p < 0.001 | −1.0 |
| IL-10 | Serum | Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 2.2 (1.0–4.8)† pg/mL | 4.6 (3.3–6.3)† pg/mL | Yes; OA < controls; p = 0.029 | N/A |
| IL-12p70 | Serum | Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 0.6 (0.4–1.1)† pg/mL | 2.7 (1.5–5.0)† pg/mL | Yes; OA < controls; p = 0.007 | N/A |
| KS | Serum | Sweet et al., 1988 [44] | JSN, subchondral sclerosis, osteophytes | 31 (71 ± 4; 8:23) | 41 (62 ± NS; 22:19) | 475 (± 178) | 261 (± 51) | Yes; OA > controls; p < 0.001 | 4.2 |
| NO | Serum | Salvatierra et al., 1999 [38] | ACR criteria | 27 (60 ± 5; 10:17) | 12 (51 ± 7; 3:9) | 2.6 (± 0.5) μmol/L | 1.4 (± 0.6) μmol/L | Yes; ambulatory OA > control; p < 0.0001; yes; surgical > control; p < 0.0001 | 2.0 |
| MMP-9 | Serum | Hulejová et al., 2007 [21] | THA for OA K-L grade 3–4 | 55 (68 ± 10; 9:46) | 30 (56 ± 11; 8:22) | 259.8 (± 33.5) pg/mL | 68.2 (± 5.3) pg/mL | Yes; OA > controls; p < 0.001 | 36.2 |
| sIL-4R | Serum | Silvestri et al., 2006 [40] | K-L grade 3–4 | 34 (68 ± 10; 15:19) | 38 (67 ± 10; 8:30) | Median 49 (NS) pg/mL | 25.6 (NS) pg/mL | Yes; OA > controls; p < 0.001 | N/A |
| TIMP-1 | Serum | Chevalier et al., 2001 [9]* | K-L grade 2–3; ACR criteria | 29 (59 ± 11; 13:16) | 225 (40 ± 12; 109:116) | 529 (± 197.9) | 617 (± 107) | No; NS | −0.8 |
| Hulejová et al., 2007 [21] | THA for OA K-L grade 3–4 | 55 (68 ± 10; 9:46) | 30 (56 ± 11; 8:22) | 1.11 (0.06) | 1.14 (0.06) | No; NS | −0.5 | ||
| IL-6 | Serum | Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 4.4 (2.8–6.9)† pg/mL | 3.6 (2.1–6.1)† pg/mL | No; p = 0.6 | N/A |
| IL-1β | Serum | Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 0.4 (0.1–1.0)† pg/mL | 0.5 (0.3–0.9)† pg/mL | No; p = 0.6 | N/A |
| IL-8 | Serum | Koorts et al., 2012 [27] | Clinical diagnosis | 7 (NS; NS) | 19 (NS; NS) | 16.4 (11.4–23.5)† pg/mL | 14.2 (8.8–22.9)† pg/mL | No; p = 0.7 | N/A |
* Studies repeated in other categories; †geometric mean; AAT = alpha-1 antitrypsin; ACR = American College of Rheumatology; CAT-D = cathepsin D; Cr = creatinine; CRP = C-reactive protein; CTX-II = type II collagen telopeptide; DPD = deoxypyridinoline; Helix-II = type II collagen helical telopeptide; IL = interleukin; JSN = joint space narrowing; K-L = Kellgren-Lawrence; KS = keratan sulfate; Ln = natural log; MMP = matrix metalloproteinase; N/A = not applicable; NO = nitrous oxide; NS = not specified; OA = osteoarthritis; PYD = pyridinoline; sIL-4R = soluble IL-4 receptor; TGF-β1 = transforming growth factor β1; TIMP-1 = TIMP metalloproteinase inhibitor 1; XR = radiograph; YKL-40 = human cartilage glycoprotein 39.