Bone Disease in Newly Diagnosed Lupus Nephritis Patients

Abstract

IntroductionBone 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.MethodsWe 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.ResultsLN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m2. They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, 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.±9.1 vs. 22.9±5.3 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 (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls.DiscussionNewly 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.

Vitamin D in SLE: a role in pathogenesis and fatigue? A review of the literature

“…59 In a prospective cohort study of 653 SLE patients, significantly higher levels of serum TNF-a were seen in SLE patients compared to non-autoimmune controls. 60 In addition, a significant inverse correlation between serum 25(OH)D and TNF-a levels was observed in patients with lupus nephritis, 61 suggesting that vitamin D deficiency may possibly be linked to elevated TNF-a levels in SLE patients.…”

Risk factors for bone loss in juvenile-onset systemic lupus erythematosus: a prospective study

“…Other studies have shown the relationship of SLE nephritis with bone mass loss apparently without the influence of glucocorticoid use. 35,36 One study with 15 newly diagnosed lupus nephritis (≤2 months) patients within a mean of 34-day glucocorticoid initiation therapy showed that these patients presented with significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate on bone biopsy, associated with an increased eroded surface and osteoclast surface. 35 Although these patients had been exposed to glucocorticoid use, this study showed a higher expression of monocyte chemotactic protein in bone tissue of lupus nephritic patients that is associated with renal disease activity.…”

Efeitos in vitro de soro de pacientes com nefrite lúpica ativa em células de linhagem osteoblástica humana hFOB 1.19

“…Portanto, sumariamente, osteoblastos cultivados em um microambiente com elevados níveis de TNF-, IL-6 e talvez IL-2, como nossas culturas de hFOB 1.19, poderia induzir a produção de RANKL, suportando nosso achado de mRNA de RANKL elevado, e poderia também inibir a expressão de OPG, substanciando nossa detecção de menor nível da proteína OPG na scélulas NL. Tomados conjuntamente, esses achados podem suportar as alterações ósseas detectadas em biópsia de pacientes com diagnóstico recente de nefrite lúpica 42 .…”