title: Impaired fracture healing associated with amino acid disturbances.
abstract: BACKGROUND
  Five percent to 10% of all fracture patients experience an inadequate healing process that results in a nonunion of fracture parts. Previous experimental studies have indicated the importance of sufficient nitric oxide production from arginine during normal fracture healing. However, during conditions of stress, such as inflammation, arginine availability can become limited, which may lead to a nonunion as a result of insufficient callus formation.
  
  
  OBJECTIVE
  The aim of this study was to measure callus and plasma amino acid concentrations in patients with and without a fracture nonunion.
  
  
  METHODS
  Amino acid concentrations in plasma and callus were measured with HPLC in atrophic nonunions (n = 12) and compared with those in hypertrophic nonunions (n = 12), acute fractures (n = 15), and healed fractures (n = 8).
  
  
  RESULTS
  Arginine (61 compared with 180 μmol/mg; P < 0.0001), citrulline (13 compared with 44 μmol/mg; P < 0.0001), and ornithine (25 compared with 149 μmol/mg; P < 0.0001) in callus were significantly lower in atrophic-nonunion patients than in healed-fracture patients. In hypertrophic nonunions, arginine was significantly higher and ornithine was lower than in healed fractures. Plasma arginine concentrations were significantly lower in patients with hypertrophic nonunions (62 μmol/L; P < 0.001) and acute-fracture patients (41 μmol/L; P < 0.001) but not in atrophic-nonunion patients. Plasma ornithine concentrations were lower in all groups than in acute-fracture patients.
  
  
  CONCLUSIONS
  Amino acid concentrations were significantly changed in nonunion patients. Atrophic nonunions had lower concentrations of all amino acids, whereas hypertrophic nonunions had higher arginine and lower ornithine concentrations at fracture sites than did healed-fracture and acute-fracture patients.
authors.affiliation: Department of Surgery, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Karolina A P
authors.initials: KA
authors.lastname: Wijnands
authors.forename: Peter R G
authors.initials: PR
authors.lastname: Brink
authors.forename: Paul H E
authors.initials: PH
authors.lastname: Weijers
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: Martijn
authors.initials: M
authors.lastname: Poeze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood*; D001120:Arginine / Q000097:blood; D002146:Bony Callus / Q000254:growth & development; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D005599:Fractures, Ununited / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000596:Amino Acids; D001120:Arginine