The Role Of RANKL In Premenopausal Systemic Lupus Erythematosus Combined With Osteoporosis

Introduction Systemic lupus erythematosus(SLE) is a kind of diffuse connective tissue disease which is characterized by autoimmunity and multiple autoimmune antibodies. Multiple organs could be involved in SLE. SLE has a specific predilection in child-bearing age women. Some younger women have osteoporosis(OP) because of vasculitis, lupus nephritis, inflammatory factors stimulation and steroids use and are inclined to have symptomless bone fracture. The basic and clinical research on SLE combined with bone disease is now a focus worldwide[1-4].OP is characterized by bone mass reduction and bone tissue microarchitecture disorganization,which leads to bone friability and bone fracture. OP is ranked as OP disease, secondum OP, and idiopathetic OP. SLE and the drugs are the main causes of secondum OP.Receptor activator of nuclear factor κB ligand(RANKL) is a new member of tumour necrosis factor superfamily, play key roles in regulating physiological and pathological bone metabolism. RANKL is a cytokine in blood circulation and bone tissue. RANKL, RANK and osteoprotegerin(OPG) form RANKL/RANK/OPG complex which plays important roles in bone rowth and development, bone construction and bone remodeling. SLE patients are inclined to have OP and kidney disease, which may be associated with RANKL.In recent years, more and more researches indicated that RANKL/RANK/OPG system has closed relation with bone destruction in chronic autoimmune diseases. Furthermore, it is a key signal pathway associated with loss of bone mass. Nowadays many new findings were the reports of it in rheumatoid arthritis and ankylosing spondylitis, less in SLE. The objective of our study is to investigate the risk factors of SLE with OP and the role of RANKL in OP. We designed the present study to explore the serum RANKL levels in premenopausal SLE patients with OP.The present study examined the risk factors of SLE with OP, the serum RANKL in OP, SLE combined with OP and the control groups and the correlation between the serum RANKL and clinical features. We aimed to explore the clinical role of RANKL in premenopausal SLE combined with OP.Objective To explore the role of receptor activator of nuclear factor κB ligand(RANKL) in premenopausal systemic lupus erythematosus(SLE) combind with osteoporosis(OP).Methods A total of 66 premenopausal female patients with SLE from January 2011 to August 2014 in our hospital were collected. These patients were devided into two groups with OP(32 cases) and without OP(34 cases) and study the clinical features between the two groups to examine the risk factors of OP. The RANKL in peripheral blood serum was tested using ELISA method. The RANKL levels in OP group, non-OP group and volunteers group were analyzed with the one-factor analysis of variance. The Pearson’s correlation analysis was used to analyze the correlation between the RANKL and the clinical index. The receptor operating curve was used to analyze the sensitivity and specificity of RANKL in SLE patients combined with OP.Results In the SLE patients with OP, the course of disease, the percentage of duration of glucocorticoid application more than one year, and the occurance of lupus nephritis were significantly longer or higher than non-OP group(4.0yrs, 62.5%, 65.6% VS 2.4yrs, 35.3%, 23.5%, respectively, all with P<0.05). The relative risk of OP in SLE patients with glucocorticoid used more than 1 year or lupus nephritis are 3.1( 95%CI 1.1~ 8.3) and 6.2 respectively( 95%CI 2.1~ 18.2). The level of serum 25-hydroxy vitamin D3 of SLE patients with OP(13.5ng/ml)was significantly lower than that without OP(22.2ng/ml)(P<0.05). There were no significant difference between the two groups in the age, occurance of facial erythema, oral ulcer, alopecia, arthritis, anemia, leukopenia, thrombocytopenia, C3 decline, ANA positive, ds-DNA-positive, disease activity(SLEDAI score> 8 points) ratio and Ig G, Ig A, Ig M, ESR, blood calcium levels. The RANKL levels in SLE combined with OP group were significantly higher than those in OP group or volunteers group(590.2 pg/ml vs 329.7 pg/ml, vs 260.4 pg/ml,respectively, P<0.05). There was positive correlation between the RANKL and serum Ig A(r=0.748, P<0.01). There was negative correlation between the RANKL and serum 25-hydroxy vitamin D3 or blood calcium(r=-0.380, r=-0.423, P<0.05). When the cutoff value was 380 pg/ml, the area under the ROC was 0.716, and the sensitivity and specificity was 81.3% and 61.8%( P<0.05), respectively.Conclusions The use of glucocorticoid more than one year and lupus nephritis should be consider as the risk factors. The serum RANKL in SLE combined with OP significantly increased and could be used as a potential biomarker in SLE combined with OP.