title: Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production.
abstract: OBJECTIVE
  Cytokines stimulate nitric oxide production in bone, and high concentrations of cytokine-induced nitric oxide inhibit bone resorption in vitro. This has led to the suggestion that nitric oxide may protect against bone loss in inflammatory and infectious diseases. In this study, we sought to determine whether nitric oxide generated as the result of sepsis was associated with suppression of bone resorption in vivo.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Adult intensive care unit of a university hospital.
  
  
  METHODS
  We studied 20 consecutive patients who had been admitted to the intensive care unit because of sepsis and three who had been admitted because of trauma. Controls were 29 patients with noninflammatory musculoskeletal conditions.
  
  
  METHODS
  Standard clinical care.
  
  
  RESULTS
  Bone resorption was assessed by measurement of urinary pyridinoline and deoxypyridinoline as a ratio to urinary creatinine. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products nitrate and nitrite to urinary creatinine. Urinary nitrate and nitrite/creatinine values were significantly higher in intensive care patients with sepsis (mean +/- sem, 0.164 +/- 0.053 micromol/mmol) than in intensive care patients with trauma (0.066 +/- 0.008) and controls (0.079 +/- 0.007; p =.007 between groups). Urinary pyridinoline/creatinine values were increased in intensive care patients with sepsis (553.8 +/- 193 nmol/mmol) and trauma (238 +/- 32) compared with controls (44.7 +/- 2.6; p =.001 between groups), and similar differences between the groups were observed for deoxypyridinoline/creatinine values: intensive care patients with sepsis, 86.4 +/- 24.0; intensive care patients with trauma, 46 +/- 4.2; and controls, 10.3 +/- 0.7 (p =.001).
  
  
  CONCLUSIONS
  Critically ill patients with sepsis have increased nitric oxide production and increased bone resorption, whereas trauma patients have increased bone resorption in the presence of normal nitric oxide production. High concentrations of nitric oxide generated during the course of infection do not afford significant protection against accelerated bone resorption.
authors.affiliation: Department of Medicine and Therapeutics, University of Aberdeen Medical School, Foresterhill Aberdeen, UK.
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Smith
authors.forename: Brian
authors.initials: B
authors.lastname: Cuthbertson
authors.forename: John
authors.initials: J
authors.lastname: Harvie
authors.forename: Nigel
authors.initials: N
authors.lastname: Webster
authors.forename: Simon
authors.initials: S
authors.lastname: Robins
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000652:urine; D001862:Bone Resorption / Q000209:etiology*; D003404:Creatinine / Q000652:urine; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000652:urine; D018805:Sepsis / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism
chemical_list: D000596:Amino Acids; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C015484:pyridinoline; C036020:deoxypyridinoline; D003404:Creatinine