Soluble receptor activator of nuclear factor κB ligand/osteoprotegerin ratio is increased in systemic lupus erythematosus patients

Abstract

IntroductionSystemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG).Our aim was to assess serum OPG and soluble RANKL (sRANKL) levels as well as sRANKL/OPG ratio in female SLE patients and compare it with female controls.MethodsWe have evaluated 103 SLE patients and 114 healthy controls, all Caucasian females. All participants underwent a clinical and laboratory evaluation. sRANKL and OPG were quantified in serum by ELISA based methods. sRANKL, OPG and sRANKL/OPG ratio levels were compared between SLE patients and age, sex and race matched healthy controls. For SLE patients, a multivariate analysis was performed, to find the possible predictors of the changes in sRANKL, OPG and sRANKL/OPG ratio levels.ResultsAlthough sRANKL levels did not differ between the two groups, serum OPG was lower in SLE patients (P < 0.001). This led to an increased sRANKL/OPG ratio (P = 0.010) in the patients' group.The multivariate analysis was performed considering age and other clinical and laboratorial potential confounders for these variations in the SLE patients group. We have showed that age (P = 0.001) and levels of anti-Sm antibodies (P = 0.016) were independent predictors of sRANKL/OPG ratio variations in SLE patients. No relationship with therapy or disease activity measured by SLEDAI2K was found.ConclusionsThese results are suggestive of increased osteoclastic stimuli driven by the SLE disease mechanisms.

Prevention and Treatment of Bone Changes Associated with Exposure to Glucocorticoids

“…Similar to RA, SLE is associated with increased production of pro-inflammatory cytokines that affect the RANKL pathway 6 . Bone micro-architecture and strength may be modified in patients with SLE, even if untreated with glucocorticoids 7 .…”

Lower P1NP serum levels: a predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients

“…As mentioned, glucocorticoids can favor bone resorption by increasing RANKL/OPG ratio. One study found that SLE patients have lower OPG levels, compared to controls but previous reports of these markers in SLE patients did not evaluate bone mineral density [31,32].…”

Romatizmal Hastalıklarda Osteoporozun Etiyopatogenezi

“…Sistemik enflamasyon, osteoklastik aktiviteyi arttırarak ve osteoblastik aktiviteyi azaltarak kemik kaybına katkıda bulunmaktadır. SLE'li hastalarda kemik yeniden yapılanmasında önemli olan RANKL/OPG oranında artış saptanmış, artmış osteoklastik uyarının kemik kaybında etkili olduğu ifade edilmiştir (58). Aktif hastalıkta, TNF seviyeleri ve oksidize LDL seviyelerinde artış olduğu belirtilmiştir (10).…”