title: Bone disease in newly diagnosed lupus nephritis patients.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  LN 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Aline Lázara
authors.initials: AL
authors.lastname: Resende
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Luciene Machado
authors.initials: LM
authors.lastname: dos Reis
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Cristiane Bitencourt
authors.initials: CB
authors.lastname: Dias
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Melani Ribeiro
authors.initials: MR
authors.lastname: Custódio
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Vanda
authors.initials: V
authors.lastname: Jorgetti
authors.affiliation: Nephrology Division, Sao Paulo University Medical School, Sao Paulo, Brazil.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Woronik
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D001847:Bone Diseases / Q000097:blood* / Q000175:diagnosis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood* / Q000175:diagnosis; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D053245:RANK Ligand / Q000097:blood; D014807:Vitamin D / Q000097:blood; D055815:Young Adult
chemical_list: D000596:Amino Acids; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053245:RANK Ligand; D014807:Vitamin D; C036020:deoxypyridinoline