Background/Purpose:

Fat tissue synthesizes and releases a series of biologically active substances (adipokines), which are involved in bone metabolism through effects on bone formation and resorption. Leptin, one of the most important adipokines derived from fat tissue, seems to be responsible for the major part of effects of adipose tissue on bone.

The aim of this study was to investigate the role of leptin serum levels as a predictor of radiographic spinal progression in patients with ankylosing spondylitis (AS).  

Methods:

Altogether 120 patients (82 men and 38 women) from the Effects of NSAIDs on Radiographic Damage in AS (ENRADAS) trial who completed the study per protocol were included into the analysis. Spinal radiographs (lumbar and cervical spine, lateral views) were scored independently by two trained readers in a concealed and randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scoring system. Radiographic spinal progression was defined as 1) mSASSS worsening by ≥2 units after 2 years, and 2) development of at least one new syndesmophyte or progression of existing syndesmophytes (i.e., formation of a bridging syndesmophyte) after 2 years. Leptin serum levels were measured at baseline by ELISA.

Results:

Mean baseline leptin levels were significantly lower in patients with mSASSS worsening by ≥2 units after 2 years (n=29) as compared to those without progression (n=91): 10.3±8.8 vs. 15.9±13.7 ng/ml, respectively, p=0.002, and in patients with syndesmophyte formation (n=25) as compared to those without syndesmophyte formation (n=95): 10.1±9.6 vs. 15.7±13.4 ng/ml, respectively, p=0.002. This difference was especially evident in males, but not in females. Remarkably, in females the serum level of leptin at baseline was significantly higher than in males: 30.0±21.0 vs. 10.7±8.2 ng/ml, p<0.001.

In the ROC analysis leptin had an area under the curve (AUC) of 0.69 (95% CI 0.57-0.81) for no mSASSS worsening by ≥2 units and 0.70 (95% CI 0.57-0.82) for no syndesmophyte formation. Leptin serum level of >7.5 ng/ml had a sensitivity of 78%, a specificity of 55%, and an odds ratio (OR) = 4.2 (95% CI 1.7-10.6) as a protector from mSASSS worsening by ≥2 units after 2 years (after adjustment for baseline syndemophytes, elevated CRP, smoking, body mass index, sex, and NSAIDS intake index, the OR increased to 9.2, 95% CI 2.5-34.0). The same serum level of leptin demonstrated a sensitivity of 77%, a specificity of 56%, and an OR = 4.2 (95% CI 1.7-10.6) as a predictor from syndesmophyte formation (after adjustment for the same variable as above, OR = 11.7, 95% CI 2.8-47.8).

In the logistic regression analysis with baseline leptin serum level as a scale variable, a protective role of higher leptin serum level regarding radiographic spinal progression was confirmed: OR = 1.15 (95% CI 1.02-1.3) for no mSASSS worsening by ≥2 units, and OR = 1.28 (95% CI 1.1-1.5) for no syndesmophyte formation.

Conclusion:

Higher serum levels of leptin seem to protect patients with AS from radiographic spinal progression. Interestingly, female patients with AS have significantly higher leptin levels that might explain lesser extent of structural damage in the spine in female AS patients in general.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/higher-serum-level-of-leptin-protects-from-radiographic-spinal-progression-in-patients-with-ankylosing-spondylitis/