Table 3.

Markers of radiographic severity and progression

Marker	Comment	Ref.
C-reactive protein, ESR	Elevated CRP associated with radiographic severity on spine X-rays and elevation of CRP and ESR predict future radiographic progression in the sacroiliac joints and spine in AS patients.	[61]
Vascular endothelial growth factor (VEGF)	Mean baseline VEGF values were significantly higher in patients with mSASSS worsening by ≥2 units after 2 years than in those without progression and in patients with syndesmophyte formation as compared with those without new bone formation.	[56–58]
Matrix metalloproteinase 3 MMP3	Serum MMP is an independent predictor of structural damage progression in patients with ankylosing spondylitis.	[45]
C-terminal cross-linking telopeptide of type I (CTX-I) and type II (CTX-II) collagen	Baseline radiological damage correlated with CTX-II but not with CTX-I levels. There was a negative correlation between CTX-I and BMD of the trochanter. In multivariate analyses, CTX-II significantly and independently contributed to explaining variation in radiological damage and progression.	[59–61]
Circulating protein fragments of cartilage and connective tissue degradation (C2M and C3M)	Circulating protein fragments of cartilage and connective tissue degradation (C2M and C3M) were significantly higher in serum samples from AS patient than from healthy controls. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80 % of the progressors and 61 % of the non-progressors. It needs further confirmation.	[62]
Degraded citrullinated vimentin fragments (VICM)	VICM levels were higher in AS patients than in healthy controls—those with highest levels of VICM levels had the highest mSASSS score. VICM levels associated with radiographic progression after 2 years.	[60]
Sclerostin	Serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Of particular note, low serum sclerostin level in patients with AS was significantly associated with the formation of new syndesmophytes. It was not seen in other studies	[46, 50, 63–66]
Dickkop-1 (Dkk-1)	AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signaling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis.	[46, 50, 51, 66–69]
Osteoprotegerin (OPG)	OPG levels were higher in AS patients than in the controls, decreasing significantly after the 3-month anti-TNF-α therapy.	[50, 69]
Osteocalcin	Osteocalcin levels were higher in AS patients than in controls. Osteocalcin level increased after the 3-month anti-TNF-α therapy.	[61, 70–72]
Fetuin-A	Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls. However, fetuin-A was not different between the patients without syndesmophytes and controls.	[65]
Adipokines	Serum levels of adipokines were inconsistently associated with disease activity. One study showed an association of leptins with syndesmophyte formation and another elevated levels of visfatin with radiographic progression in AS.	[73–75]