Background Inflammation in SLE is associated with an increase in circulating levels of pro-inflammatory cytokines including receptor activator for nuclear factor-κB ligand (RANKL), inducing osteoclasts differentiation and bone resorption. On the other hand, glucocorticoid (GC)can increase osteoclast lifespan by upregulating RANKL and suppressing osteoprotegrin (OPG). Inflammation and the use of GC in SLE may also inhibit bone formation by inducing the expression of an antagonist of the Wnt pathway - dickkopt-1 (Dkk-1), preventing osteoblast differentiation. Increased RANKL/OPG ratio and Dkk-1 expression had been described in SLE.
Objectives 1) to evaluate the changes of volumetric BMD (vBMD) and bone microstructure by high resolution peripheral quantitative CT (HR-pQCT) over time in SLE patients on long-term GC and 2) to determine whether imbalance between RANKL/OPG and Dkk-1 level can predict changes in vBMD and bone microstructure.
Methods This was a one-year prospective observational study in female SLE patients on long-term GC. Changes in bone geometry, vBMD and microstructure at distal radius were evaluated by HR-pQCT; and changes in aBMD were measured by dual energy x-ray absorptiometry (DXA) at total hip, lumbar spine and distal radius. Serum levels of RANKL, OPG and Dkk-1 were measured by ELISA. Potential risk factor of bone loss including age, menopausal status and other variables were analyzed using multiple regression analysis.
Results A total of 180 consecutive SLE patients were recruited at baseline, and 165 completed the study. After 12 months, no significant change in aBMD at the three measured sites was observed. Using HR-pQCT, trabecular area and cortical microstructure (cortical area, perimeter and thickness [CtTh]) decreased significantly, while trabecular vBMD and meta-trabecular vBMD (adjacent to endocortical bone) significantly improved, respectively. Subgroup analysis revealed that aBMD at all measured sites and CtTh reduced significantly in postmenopausal patients. In contrast, aBMD and CtTh did not alter significantly but vBMD of cortical and trabecular bone significantly increased in premenopausal patients. Multiple regression analysis showed baseline Dkk-1 and the ratio of RANKL/OPG were independent predictors for the change in cortical area (β=-0.0003 and β=-33.1, respectively) and in CtTh (β=-0.0003 and β=-35.8, respectively). RANKL/OPG was independent predictor for percentage change in cortical vBMD (β=-12.85).
Conclusions Deteriorated cortical bone geometry and mirostructure presenting as cortical bone ‘trabecularization’ were in SLE patients on long-term GC, while both cortical and trabecular bone were preserved in premenopausal subgroup, suggesting estrogen may reserve bone loss in SLE with GC. Dkk-1 and RANKL/OPG are independent predictors for changes in cortical density and structure, suggesting that bone loss in SLE with GC both by increasing osteoclastic resorption and by reducing osteoblastic formation.
Disclosure of Interest: None Declared