Experimental Assessments:

1
Cyclic Compression Inhibits Orchidectomy-Induced
Osteopenia of the Mouse Tibia J Christopher
Fritton 1,2, Elizabeth R Myers2, Timothy M
Wright2, Marjolein C H van der Meulen1,2 1
Biomedical Engineering, Cornell University,
Ithaca NY 2 Musculoskeletal Integrity Program,
Hospital for Special Surgery, New York NY




Introduction

• Healthy skeleton responds to biophysical stimuli,
  particularly time-varying mechanical loading
• Whether osteopenia can be prevented by mechanical
  loading is unknown
• Previously developed in vivo loading model in the
  mouse Fritton et al. 2003
• Administer well defined compressive loads to
  tibia
• Produce site-specific increases in bone mass
  greater effect at metaphysis than diaphysis

Cyclic mechanical loading can inhibit
development of osteopenia following hormonal
compromise by orchidectomy in the mouse tibia
Hypothesis
Experimental Assessments Microcomputed
tomography of tibia Bone mineral content
(BMC) Cortical moments of inertia Cancellous
bone volume fraction, trabecular thickness,
separation Site-specific volumes of interest
(VOIs) Cortical middiaphysis Corticocancello
us proximal metaphysis Statistical
Analysis Effects of loading, ORX by two
factor ANOVA (a 0.05)
Experimental Design 10w old male C57Bl/6
mice Basal group (n12) to document initial
properties 2 treatment factors (n12/group)
Osteopenia Applied cyclic loading Osteopeni
a induced by hormonal compromise Orchidectomy
(ORX) at 10 weeks of age Surgical (sham)
controls Applied cyclic loading Left limb
loaded Right limb control Loading initiated
3 days after ORX 6 weeks of loading
applied Triangle waveform 2/sec strain rate
1200 cycles, 4 cycles/sec, 5 days/week
Methods
Results
Diaphyseal Moments of Inertia

• Summary
• Significant loss of bone mass with ORX relative
  to sham control limbs
• Middiaphysis no effect
• Metaphysis -80 BV/TV, -23 BMC
• Significant effect of loading in ORX limbs
• Middiaphysis 22 BMC
• Metaphysis 275 BV/TV, 58 BMC
• Effect of loading similar in ORX and sham mice
• 2 increase in tibial length, 10 increase in
  body mass with age (basal vs. sham)
• No effect of limb side (basal left vs. right)

Metaphyseal Bone Mass Architecture

• Mechanical loading altered both bone mass and
  cancellous architecture in osteopenic mice
• Increased bone volume fraction, bone mineral
  content to sham levels
• Increased trabecular thickness above sham levels
• Effect of ORX and mechanical loading
  site-specific
• Greater effect at metaphysis than diaphysis of
  tibia
• Sensitivity to loading is not altered following
  hormonal compromise by orchidectomy in the mouse

• Cyclic compression maintains bone mass but not
  architecture in the mouse tibia after
  orchidectomy
• Mechanical loading shows promise as therapy to
  prevent osteopenia at skeletal sites that are
  predominantly cancellous bone

Discussion Conclusions

References Fritton, Myers, Wright, van der Meulen
(2003) Trans Orthop Res Soc 28 83
Acknowledgments NASA NGT5-50375, NIH P30-AR046121
(Imaging Core) Sigma Xi Research Foundation,
Kirby and Clark Foundations
NASA Bioastronautics Investigators Workshop,
Galveston TX, 2005