title: Knee loading stimulates cortical bone formation in murine femurs.
abstract: BACKGROUND
  Bone alters its architecture and mass in response to the mechanical environment, and thus varying loading modalities have been examined for studying load-driven bone formation. The current study aimed to evaluate the anabolic effects of knee loading on diaphyseal cortical bone in the femur.
  
  
  METHODS
  Using a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the left knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3 consecutive days. Animals were sacrificed for examination 13 days after the last loading. The contralateral femur was used as a non-loading control, and the statistical significance of loading effects was evaluated with p < 0.05.
  
  
  RESULTS
  Although diaphyseal strains were measured as small as 12 mustrains, bone histomorphometry clearly demonstrated frequency-dependent enhancement of bone formation. Compared to a non-loading control, bone formation on the periosteal surface was significantly enhanced. The loading at 15 Hz was most effective in elevating the mineralizing surface (1.7 x; p < 0.05), mineral apposition rate (1.4 x; p < 0.001), and bone formation rate (2.4 x; p < 0.01). The loading at 10 Hz elevated the mineralizing surface (1.4 x; p < 0.05), mineral apposition rate (1.3 x; p < 0.01), and bone formation rate (1.8 x; p < 0.05). The cross-sectional cortical area and the cortical thickness in the femoral diaphysis were significantly increased by loading at 10 Hz (both 9%) and 15 Hz (12% and 13%, respectively).
  
  
  CONCLUSIONS
  The results support the anabolic effects of knee loading on diaphyseal cortical bone in the femur with small in situ strain, and they extend our knowledge on the interplay between bone and joints. Strengthening the femur contributes to preventing femoral fractures, and the discovery about the described knee loading might provide a novel strategy to strengthen osteoporotic bones. Further analyses are required to understand the biophysical and molecular mechanism behind knee loading.
authors.affiliation: Departments of Biomedical Engineering, Indiana University--Purdue University Indianapolis, Fesler Hall 115, 1120 South Drive, Indianapolis IN 46202, USA. pizhang@iupui.edu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Shigeo M
authors.initials: SM
authors.lastname: Tanaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000379:methods; D016723:Bone Remodeling / Q000502:physiology; D005260:Female; D005269:Femur / Q000166:cytology / Q000502:physiology*; D007719:Knee Joint / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology