Serum RANKL, osteoprotegerin (OPG) and RANKL/OPG ratio in children with systemic lupus erythematosus

Abstract

Background Systemic lupus erythematosus (SLE) patients have lower bone mineral density (BMD) compared with healthy individuals because of general, genetic, disease and medication-related factors. The disturbance of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio has been reported to be associated with low BMD in many disorders in adults and children alike. Objectives The objectives of this study were (i) to assess serum OPG, RANKL and RANKL/OPG ratio levels in SLE children and controls, (ii) to determine whether the cumulative glucocorticoid (CGCS) dose had any effect on the concentration of serum RANKL, OPG and RANKL/OPG ratio, and (iii) to determine the relation of these parameters to BMD. Methods We evaluated 50 SLE children and 50 age- and sex-matched healthy controls. RANKL and OPG were assessed in serum and compared between patients and controls. For SLE patients, a univariate followed by multivariable analysis were carried out to detect the possible predictors of the changes in RANKL, OPG and RANKL/OPG ratio levels. Lumbar BMD for all patients was assessed by dual-energy X-ray absorptiometry (DXA) scan and then correlated to different probable correlated factors. Results RANKL, OPG and RANKL/OPG ratio were significantly higher in SLE patients ( p ≤ 0.001). Univariate analysis showed significant correlations of RANKL with CGCS ( p ≤ 0.001) and with DXA scan z-score ( p = 0.007): OPG was significantly correlated to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ( p = 0.001) and anti-double-stranded DNA ( p = 0.001), whereas RANKL/OPG was significantly correlated to duration of illness and DXA z-score ( p = 0.002). The multivariable analysis showed that DXA z-score was an independent predictor of RANKL and RANKL/OPG ratio ( p = 0.019 and 0.008, respectively), whereas SLEDAI score was an independent predictor of OPG levels. BMD was negatively correlated to disease duration ( p = 0.008) and CGCS dose ( p = 0.015), but no significant correlation has been found between BMD and cumulative SLEDAI score ( p = 0.29). Conclusions Serum RANKL/OPG ratio is elevated in Egyptian children with SLE and is considered a risk factor for reduced bone mass in these children. Other risk factors for low BMD include high CGCS dose and disease duration, supporting that osteoporosis in SLE is multifactorial.