Relationship between serum adipokine levels and radiographic progression in patients with ankylosing spondylitis

Abstract

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8–10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Inflammation, obesity and rheumatic disease: common mechanistic links. A narrative review

“…38 Furthermore, and as suggested above, it is likely that adiponectin is strongly associated with early radiographic disease 45 and radiographic progression in RA, 26 irrespective of the metabolic status of the patient. 38,45 In AS, adiponectin serum levels seem to be comparable between patients and healthy individuals 40–42 and do not correlate with disease activity. It has been suggested that high-molecular-weight adiponectin might offer protection from radiographic progression in these patients.…”

“…Although not supported by all studies, 32 resistin seems to be increased in serum from AS patients and associated with radiological progression of the disease. 40,41,50 It is rather unclear if there is any correlation between its levels and disease activity. A study in PsA patients suggested that resistin is also increased in these patients.…”

Adipokines and Chronic Rheumatic Diseases: from Inflammation to Bone Involvement

“…The first stage is the inflammation driven mainly by TNFα, which causes erosions in cartilage and bone; these lesions are then filled in by fibrous tissue, which is later ossified in the last stage leading to abnormal bone outgrowth. New bone formation is actually a hallmark of the disease and is represented by syndesmophytes, bone bridges between the vertebral bodies and subsequent complete ankylosis of the spine [51,86]. Undoubtedly, these productive bone lesions typical of AS deeply impact quality of life in the long-term, since they irreversibly constrain mobility of the spine [87].…”

Mini-Review: The Contribution of Adipokines to Joint Inflammation in Inflammatory Rheumatic Diseases

“…In parallel, the question of the potential influence of adipokines on the progression of spinal ossifications has consistently been examined. Certain studies reported that serum leptin was more elevated in patients with syndesmophytes compared to patients without ( 72 , 73 ) and one study reported the association between the changes in serum leptin at 2 years and radiographic progression ( 74 ). In parallel, visfatin but not resistin or adiponectin have been linked to worsening of the radiographic spinal ossification score (modified stoke ankylosing spondylitis spinal score [mSASSS]) ( 75 ).…”