Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production

Lorna Margaret Smith, Brian Cuthbertson, Nigel Robert Webster, J. Harvie, S. P. Robins, S Ralston

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Design: Observational study.

Setting: Adult intensive care unit of a university hospital.

Patients: 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.

Interventions: Standard clinical care.

Measurements and Main 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 mumol/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. (Crit Care Med 2002; 30:837-840).

Original languageEnglish
Pages (from-to)837-840
Number of pages3
JournalCritical Care Medicine
Volume30
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • bone
  • nitric oxide
  • osteoporosis
  • bone resorption
  • biochemical markers
  • sepsis
  • cytokine
  • inflammation
  • collagen
  • osteoclast
  • OSTEOBLAST-LIKE CELLS
  • SYNTHASE EXPRESSION
  • IMMOBILIZATION
  • MOUSE

Cite this

Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production. / Smith, Lorna Margaret; Cuthbertson, Brian; Webster, Nigel Robert; Harvie, J.; Robins, S. P.; Ralston, S.

In: Critical Care Medicine, Vol. 30, No. 4, 2002, p. 837-840.

Research output: Contribution to journalArticle

Smith, Lorna Margaret ; Cuthbertson, Brian ; Webster, Nigel Robert ; Harvie, J. ; Robins, S. P. ; Ralston, S. / Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production. In: Critical Care Medicine. 2002 ; Vol. 30, No. 4. pp. 837-840.
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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.Design: Observational study.Setting: Adult intensive care unit of a university hospital.Patients: 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.Interventions: Standard clinical care.Measurements and Main 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 mumol/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. (Crit Care Med 2002; 30:837-840).",
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TY - JOUR

T1 - Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production

AU - Smith, Lorna Margaret

AU - Cuthbertson, Brian

AU - Webster, Nigel Robert

AU - Harvie, J.

AU - Robins, S. P.

AU - Ralston, S

PY - 2002

Y1 - 2002

N2 - 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.Design: Observational study.Setting: Adult intensive care unit of a university hospital.Patients: 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.Interventions: Standard clinical care.Measurements and Main 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 mumol/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. (Crit Care Med 2002; 30:837-840).

AB - 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.Design: Observational study.Setting: Adult intensive care unit of a university hospital.Patients: 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.Interventions: Standard clinical care.Measurements and Main 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 mumol/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. (Crit Care Med 2002; 30:837-840).

KW - bone

KW - nitric oxide

KW - osteoporosis

KW - bone resorption

KW - biochemical markers

KW - sepsis

KW - cytokine

KW - inflammation

KW - collagen

KW - osteoclast

KW - OSTEOBLAST-LIKE CELLS

KW - SYNTHASE EXPRESSION

KW - IMMOBILIZATION

KW - MOUSE

U2 - 10.1097/00003246-200204000-00020

DO - 10.1097/00003246-200204000-00020

M3 - Article

VL - 30

SP - 837

EP - 840

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 4

ER -