title: Pro-inflammatory cytokines and bone fractures in CKD patients. An exploratory single centre study.
abstract: BACKGROUND
  Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients.
  
  
  METHODS
  In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months) belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate) and inflammatory cytokines (TNF-α, IL-6, CRP). Patients were followed-up until the first non traumatic fracture.
  
  
  RESULTS
  During follow-up (median: 74 months; range 0.5 -84.0) 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95-741 vs 135 pg/ml IQ: 53-346; p = 0.04) and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02). Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005) predicted bone fractures on univariate Cox's regression analysis. In restricted (bivariate) models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures.
  
  
  CONCLUSIONS
  In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.
authors.affiliation: Nephrology, Dialysis, Hypertension and Renal Transplantation Unit Azienda Ospedaliera, Via vallone Petrara, 89124, Reggio Calabria, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panuccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Enia
authors.forename: Rocco
authors.initials: R
authors.lastname: Tripepi
authors.forename: Roberta
authors.initials: R
authors.lastname: Aliotta
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D015984:Causality; D015897:Comorbidity; D016207:Cytokines / Q000276:immunology*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000453:epidemiology* / Q000276:immunology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000276:immunology*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D016207:Cytokines