title: Increased levels of biochemical markers of bone turnover in relation to persistent immune activation in common variable immunodeficiency.
abstract: BACKGROUND
  Based on the involvement of cytokines and growth factors in bone homeostasis, we hypothesised that patients with common variable immunodeficiency (CVI), characterised by persistent immune activation in vivo, may have disturbed bone metabolism as evaluated by biochemical markers of bone turnover.
  
  
  METHODS
  Serum levels of tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), bone-specific alkaline phosphatase (B-ALP), osteocalcin, carboxyterminal crosslinking telopeptide of type I collagen (CTX-I), insulin-like growth factor (IGF)-I and IGF binding protein-3 (IGFBP-3) were measured in 25 patients with CVI and compared to 25 age- and sex-matched healthy controls.
  
  
  RESULTS
  Patients with CVI had significantly higher serum levels of CTX-I and B-ALP, and significantly lower serum levels of IGF-I and IGFBP-3 compared to controls as shown in cross-sectional, and as for B-ALP and CTX-I, also during longitudinal testing. No differences were observed for osteocalcin between the two groups. The elevated B-ALP and decreased IGF-I and IGFBP-3 levels were most pronounced in a subgroup of CVI patients characterised by persistent activation of proinflammatory cytokines in vivo. Raised B-ALP and decreased IGF-I and IGFBP-3 were also significantly correlated with enhanced IL-6 and TNF-alpha levels in these patients.
  
  
  CONCLUSIONS
  The present study suggests that persistent immune activation in vivo, with raised levels of proinflammatory cytokines, may be related to disturbed bone homeostasis in CVI patients, further supporting an interaction between immune related mediators and bone metabolism in humans.
authors.affiliation: Research Institute for Internal Medicine, National University Hospital, Oslo, Norway. thor.ueland@rikshospitalet.no
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: J
authors.initials: J
authors.lastname: Bollerslev
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers; D001842:Bone and Bones / Q000276:immunology* / Q000378:metabolism*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D010865:Pilot Projects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D000469:Alkaline Phosphatase