Bone disease in newly diagnosed lupus nephritis patients

Abstract

Introduction: Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology. Methods: We studied 15 pre-menopausal patients with #2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D3 [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis. Discussion: Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. Glucocorticoid use, vitamin D insufficiency and inflammation might be involved in the physiopathology of bone metabolism disturbance. Results: LN patients presented a mean age of 29.5610 years, a proteinuria of 4.762.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31-87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34612 days. All patients presented vitamin D insufficiency (9.964.4 ng/ml, range 4-20). Urinary MCP1 correlated negatively with 25(OH)D (r =20.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.69.1 vs. 22.965.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient's bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.6160.82 vs. 1.0860.50%, p = 0.003), and an increased expression of Receptor Activator of NF-kB ligand (RANKL) (1.7660.92 vs. 0.4160.28%, p,0.001) when compared to controls.