Table 5.

Validation studies of CTX-I as a prognostic biomarker for structural damage in RA

Study	Number of cases	Findings	Adjustments	Controls for treatment effect	Validated outcome measure used	Study design
Garnero et al. (1999)55	318	CTX-I levels were higher in patients with destructive arthritis	Age, gender, menopausal status	Controlled for corticosteroid and methotrexate use	Larsen wrist score	Cross-sectional
Garnero et al. (2002)56	110	Higher levels of CTX-I predicted more rapid progression, but only in those without damage at baseline	Baseline modified Sharp score, ESR, DAS28, seropositivity	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (median 4 years)
Landewé et al. (2004)57	110	Baseline CTX-I levels and early changes in CTX-I levels were not associated with change in damage	Baseline modified Sharp score, ESR, DAS28, seropositivity	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (median 4 years)
Jansen et al. (2004)58	279	Higher levels of CTX-I were not associated with change in damage	Age, ESR, DAS28, seropositivity, physical function	None	Modified Sharp score	Longitudinal (2 years)
Forsblad d'Elia et al. (2004)59	88	Change in CTX-I levels over 24 months was not correlated with change in damage score	None	None	Larsen score	Longitudinal (2 years)
Syversen et al. (2009)60	238	Higher levels of CTX-I were weakly associated with change in damage score	Baseline modified Sharp score, CRP, seropositivity	None	Modified Sharp score	Longitudinal (10 years)
Wislowska et al. (2009)61	50	Levels of CTX-I were lower in patients with more joint damage	Age, gender, height, body mass index, joint counts, ESR, CRP	Controlled for corticosteroid use	Larsen score	Cross-sectional
Van Tuyl et al. (2010)62	67	Higher baseline levels of CTX-I were associated with more rapid progression	Baseline modified Sharp score, ESR, seropositivity, RANKL:osteoprotegerin ratio	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (11 years)

Abbreviations: CTX-I, C-terminal crosslinked telopeptide of type I collagen; CRP, C-reactive protein; DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor κB ligand.