title: Hyperhomocysteinemia is associated with impaired fracture healing in mice.
abstract: Hyperhomocysteinemia (HHCY) has been shown to disturb bone metabolism and to increase the incidence of osteoporosis and osteoporotic fractures. However, there is a complete lack of information on whether these metabolic alterations affect bone repair. The aim of this study was to analyze the impact of HHCY on fracture healing. One group of mice was fed a homocystine-supplemented diet (n = 12), whereas another group received the accordant standard diet for control (n = 13). Four weeks after the stable fixation of a closed femoral fracture, animals were killed to prepare bones for histomorphometric and biomechanical analyses. In addition, blood samples were obtained to evaluate serum concentration of homocysteine (HCY). Quantitative analysis of blood samples revealed severe HHCY as indicated by significantly increased serum concentrations of HCY in animals fed the homocystine-supplemented diet (102.2 +/- 64.5 micromol/l) compared to controls (2.8 +/- 1.5 micromol/l). Biomechanical evaluation of bone repair revealed significantly decreased bending stiffness of the femora of homocystine-fed animals (45.5 +/- 18.2 N/mm) compared with controls (64.6 +/- 15.8 N/mm). Histomorphometric analysis demonstrated a slightly smaller callus diameter in HHCY animals but no significant differences in the tissue composition of the callus. In conclusion, the homocystine-supplemented diet leads to severe HHCY, which is associated with an impaired biomechanical quality of the healing bone.
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University of Ulm, Helmholtzstrasse 14, Ulm 89081, Germany. lutz.claes@uni-ulm.de
authors.forename: L
authors.initials: L
authors.lastname: Claes
authors.forename: J
authors.initials: J
authors.lastname: Schmalenbach
authors.forename: M
authors.initials: M
authors.lastname: Herrmann
authors.forename: I
authors.initials: I
authors.lastname: Olkü
authors.forename: P
authors.initials: P
authors.lastname: Garcia
authors.forename: T
authors.initials: T
authors.lastname: Histing
authors.forename: R
authors.initials: R
authors.lastname: Obeid
authors.forename: H
authors.initials: H
authors.lastname: Schorr
authors.forename: W
authors.initials: W
authors.lastname: Herrmann
authors.forename: T
authors.initials: T
authors.lastname: Pohlemann
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.forename: J H
authors.initials: JH
authors.lastname: Holstein
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000209:etiology*; D005269:Femur / Q000378:metabolism / Q000473:pathology*; D017102:Fracture Healing; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010024:Osteoporosis / Q000378:metabolism