Skip to main content

Table 1 Biochemical markers of bone and cartilage turnover measurable in serum, urine and synovial fluid

From: Biochemical markers of ongoing joint damage in rheumatoid arthritis - current and future applications, limitations and opportunities

Assay Target molecule Short description Evidence of potential usefulness
KS/mAb OA-1 Aggrecan Cartilage degradation. Sandwich ELISA using mAb to keratan sulfate and mAb OA-1 to AGase neoepitope ARGSVIL [143]. Detection of fragments in human synovial fluid [143] [143]
CS846 Aggrecan Cartilage turnover. mAb αHFPG-846 (IgM) recognizing chondroitin sulfate moieties on aggrecan. Manufacturer: Ibex, Canada [144, 145]
342-G2 Aggrecan Cartilage degradation. Sandwich ELISA using mAb AF28 binding to the neoepitope 342FFGVG and monoclonal antibody F78 binding to G1/G2 for detection of MMP-generated aggrecan fragments [45]
G1-G2 Aggrecan Cartilage turnover. Sandwich ELISA using mAb F78 binding to G1/G2 both as capture and detector antibody for detection of intact aggrecan and all aggrecan fragments carrying G1 and/or G2 [45, 146]
Serum CRP C-reactive protein General inflammation. CRP, an acute phase protein, the assay for which is highly sensitive to detect small changes in magnitude of inflammation [60, 126, 147149]
COMP Cartilage oligomeric protein Cartilage turnover. Competition ELISA using polyclonal antibodies [58]. However, sandwich ELISA based on two monoclonal antibodies recognizing different antigenic determinants is described [150]. Manufacturer: AnaMar Medical, Sweden [60, 61, 151155]
PICP Carboxyl terminus propeptide of type I procollagen Bone formation. RIA using polyclonal antibodies raised to fibroblast PICP digested with bacterial collagenase [156]. Manufacturer: Orion Diagnostic, Finland [156]
PINP Amino terminus propeptide of type I procollagen Bone formation. RIA using polyclonal antibodies recognizing PINP [157]. Manufacturer: Orion Diagnostic, Finland. Electrochemiluminecense using mAbs to PINP. Manufacturer: Roche Diagnostics, Germany [158]
CTX-I Type I collagen Bone resorption. A sandwich ELISA using mAb F1103 and F12, both binding to a cathepsin K-derived C-telopeptide neoepitope EKAHD-β-GGR, where D-β-G denotes an isomerized linkage between D and G [84]. Manufacturer: IDS, UK. Also available in an automated version (manufacturer: Roche Diagnostics, Germany) [8789]
NTX-I Type I collagen Bone resorption. EIA detecting a fragment of the N-telopeptide of type I collagen. Manufacturer: Inverness, US [159]
ICTP Type I collagen MMP-mediated type I collagen type degradation. RIA detecting a fragment of the C-telopeptide of type I collagen. Manufacturer: Orion Diagnostic, Finland [81, 160]
PIINP Amino terminus propeptide of type II procollagen Cartilage formation. mAb recognizing the amino acid sequence GPQPAGEQGPRGDR located in the amino-terminal propeptide of type II procollagen [46] [46]
PIIANP Amino terminus propeptide of type II procollagen, splice variant A Cartilage formation. An ELISA using rabbit polyclonal antibodies raised to recombinant exon-2 of the amino-terminal propeptide of type II procollagen [71]
CPII C-propeptide of type II collagen Cartilage formation. EIA using rabbit polyclonal antibodies binding to the C-propeptides of type II collagen, that is, a marker of collagen synthesis. Manufacturer: Ibex, Canada [161]
9A4/5109 Type II collagen Cartilage degradation. The collagenase-derived neoepitope GEGAAGPSGAEGPPGPQG775 containing the carboxyl terminus of the long three-quarter fragment. mAb 5109 detects the first underlined sequence, mAb 9A4 the second (neoepitope) [162]
CTX-II Type II collagen Cartilage degradation. Competition ELISA using mAb F4601 recognizing the C-telopeptide neoepitope EKGPDP (manufacturer: IDS, UK) and mAb 2B4 recognizing the C-telopeptide neoepitope EKGPDP [42, 163]
uTIINE Type II collagen Cartilage degradation. An LC-MS/MS assay using mAb 5109 (see above) to affinity purify fragments subjected to MS/MS. Detects a collagenase-derived 45-mer containing the carboxyl terminus of the long three-quarter fragment [53, 54]
HELIX-II Type II collagen Cartilage degradation. A competition ELISA using polyclonal rabbit antibodies recognizing the neoepitope 622ERGETGPP*GTS632, where P* denotes hydroxyproline. However, a recent publication has highlighted unspecificities [164] [164166]
C2C Type II collagen fragment Cartilage degradation. EIA using a monoclonal antibody recognizing the carboxyl terminus of the three-quarter piece of the degraded alpha1(II) chain. Manufacturer: Ibex, Canada [167, 168]
C1,C2 Type II collagen fragment Collagen degradation. EIA using rabbit polyclonal antibodies binding to the carboxy-terminal (COL2-3/4C(short)) neoepitope generated by cleavage of native human type II collagen by collagenases. Cross-reactivity to type I collagen [169]
PIIINP Amino terminus propeptide of type III procollagen Collagen type II formation. RIA using polyclonal antibodies recognizing PIIINP. Manufacturer: Orion Diagnostic, Finland [170]
Glc-Gal-PYD Glucosyl-galactosyl-pyridinoline Synovial inflammation. HPLC method for determination of the non-reducible collagen cross-linker glucosyl-galactosyl-pyridinium present in synovium and absent in bone cartilage and other soft tissue [171]
Serum HA Hyaluronic acid Cartilage turnover. Based on HA binding protein isolated from bovine cartilage. Manufacturer: for example, Pharmacia, Sweden  
YKL-40 Human glycoprotein 39 Cartilage turnover. RIA using polyclonal antibodies to a 40 kDa glycoprotein. A combined monoclonal capture and polyclonal (rabbit) detector sandwich assay is available. Manufacturer: Quidel Corporation, US [172]
OC Osteocalcin Bone formation. Numerous assays available  
MMP-3 and MMPs Varous cell types Numerous assays available [173, 174]
DKK1/Sclerostin Dkk-1 Measurement of Wnt signaling [175, 176]
TRACP 5a Macrophages Inflammation [111]
TRACP 5b Osteoclasts Osteoclast number. mAb to TRAcP 5b, which may be specific for osteoclasts but not their activity [74, 111, 177, 178]
Cat K Osteoclasts Osteoclast number [110]
  1. CRP, C-reactive protein; EIA, enzyme immunoassay; HA, hemagglutinin; LC, liquid chromatography; mAb, monoclonal antibody; MMP, matrix metalloproteinase; MS/MS, tandem mass spectrometry; RIA, radioimmune assay. Modified and extended from [179].