Developments in the scientific understanding of osteoarthritis

Table 1 Biomarkers of bone, cartilage and synovial turnover, and the BIPED classification

Tissue	Molecule	Markers of synthesis	Markers of degradation	BIPED classification
Bone	Type I collagen		PYD^a	B
			NTX-I^a,b	D
			CTX-I^a,b	P
	Noncollagenous proteins	Osteocalcin^b		P
Cartilage	Type II collagen	PIIANP^b		P
		Total PIINP		D
		PIICP^b,c		D, P
			CTX-II^a,c	D, B, P, E
			HELIX-IIa	P
			Coll 2-1^a,b	P
			Coll 2-1 NO₂^a,b	P
			C2C^a,b	P, E
			1,2C^a,b	P, E
	Aggrecan	Epitope 846 (cartilage content^c)		E
	Nonaggrecan and noncollagenous proteins		COMP^b,c	D, B, P
			Pentosidine^a,b	P
	Proteases and their inhibitors		MMPs^b	B, P, E
			TIMPs^b	B, P
Synovium	Type III collagen		GIc-GaI-PYD^a	E
	Noncolagenous proteins	YKL-40^b,c		B, E
		Hayluronic acid^b		B, P

^aUrine. ^bSerum. ^c Synovial fluid. BIPED, B (burden of disease), I (investigative), P (prognostic), E (efficacy of intervention), D (diagnostic); C1,2C, assay that detects COL2-3/4C (short) epitope; C2C, assay that detects COL2-3/4C (long) epitope; Coll 2-1, 9-amino-acid peptide of type II collagen; Coll 2-1 NO₂, nitrated form of Coll 2-1; COMP, cartilage oligomeric protein; CTX-I, carboxyl-terminal cross-linked telopeptide of type I collagen; CTX-II, C-terminal cross-linked telopeptide of type II collagen; Glc-Gal-PYD, glucosyl-galactosyl-pyridinoline; HELIX-II, helical type II collagen; MMP, matrix metalloproteinase; NTX-I, N-terminal cross-linked telopeptide of type I collagen; PIIANP, N-propeptide IIA of collagen type II; PIICP, C-propeptide of collagen type II; PIINP, N-propeptide II of collagen type II; PYD, pyridinoline; TIMP, tissue inhibitor of matrix metalloproteinase; YKL-40, cartilage glycoprotein 39. Reproduced with permission from Rouseeau and Delmas [80].