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Detecting Particle-Induced Osteolysis by Micro-CT Analysis

Detecting Particle-Induced Osteolysis by Micro-CT Analysis. Student: Bailey Lindenmaier Mentors: Dr. Russell Turner & Dr. Urszula Iwaniec Skeletal Biology Lab. Overview. Relevance of particle-induced osteolysis Obesity and factors that contribute to increased risk of osteolysis

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Detecting Particle-Induced Osteolysis by Micro-CT Analysis

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  1. Detecting Particle-Induced Osteolysis by Micro-CT Analysis Student: Bailey Lindenmaier Mentors: Dr. Russell Turner & Dr. UrszulaIwaniec Skeletal Biology Lab

  2. Overview • Relevance of particle-induced osteolysis • Obesity and factors that contribute to increased risk of osteolysis • Animal model for particle-induced osteolysis • Aims • Results and conclusions

  3. Prosthetic Joint Replacement • Approximately 600,000 joint (hip or knee) replacements are performed annually • Conditions that lead to replacement surgery: • Osteoarthritis • Osteonecrosis • Broken bone • Bone tumor • Joint replacement surgeries allow for an improved quality of life • The new joint may loosen resulting in pain and require further operations

  4. Particle-Induced Osteolysis

  5. March 3, 2010 “Concerns Over ‘Metal on Metal’ Hip Implants” By BARRY MEIER May 10, 2011 “Hip Makers Told to Study More Data” By BARRY MEIER June 25, 2011 “In Medicine, New Isn’t Always Improved” By BARRY MEIER August 22, 2011 “Hip Implant Complaints Surge, Even as the Dangers Are Studied” By BARRY MEIER and JANET ROBERTS

  6. Obesity • BMI > 30 kg/m2 • Excess body fat • Obesity is associated with: • Increased joint replacement • Increased failure rates Normal Overweight Obese

  7. von Knoch Study • Decrease in particle-induced osteolysis in obese (ob/ob) mice. von Knoch M, Jewison DE, Sibonga JD, Turner RT, Morrey BF, Loer F, Berry DJ, Scully SP. Biomaterials. 2004; 25(19):4675-4681. • Studied particle-induced osteolysis in ob/ob mice, an animal model for obesity • Surprisingly ob/ob is resistant to osteolysis • Is leptin deficiency responsible? • Adipokine • Pleiotropic hormone vs.

  8. Model of Obesity: ob/ob Mice • Leptin Deficient • Giving back leptin corrects for phenotypic abnormalities • Hyperphagic • Rapidly become obese by four weeks of age

  9. Aim • 1)Verify results obtained by von Knoch • Leptin-deficient ob/ob mice are resistant to particle-induced osteolysis • To Date: Only histological data has been collected • Difficult to define a representative “region of interest” • 2)Micro-computed tomography is a viable method to rapidly quantify particle- induced osteolysis in three dimensions Histological section of a mouse calvaria experiencing osteolysis

  10. Study Design • 4 week old ob/ob and WT mice • Polyethylene particles (a major component of artificial joints), mean diameter 5 µm, were inserted directly over the calvarial periosteum of both parietal bones • 2 week duration • Fed ad libitum, 12hr light/dark cycle, singly housed Electron microscope of polyethylene particles

  11. µ-CT Analysis • Micro - Computed Tomography • Fires an x-ray beam at a rotating specimen • X-ray attenuation is measured. • Produces 3D images for structural measurements

  12. Micro-CT Imaging of Parietal Bone 0 4 0 1 Group 1 Group 2 Group 3 Group 4 ob/ob+ Particles ob/ob WT + Particles WT

  13. Osteolytic Score of Particle-Induced Osteolysis * * * P < 0.01 within genotype (Severe) Two-way ANOVA Genotype (P = 0.028) Treatment (P < 0.001) Genotype x Treatment (P = 0.028) (None)) WT ob/ob

  14. Conclusions • Micro-computed tomography is an effective method to identify and measure osteolysis • ob/ob mice experience less particle-induced osteolysis than WT mice • Lack of leptin signaling? • Up regulated inflammatory cytokines?

  15. On the Horizon • Lab is in process of determining if leptin treatment will enhance particle-induced osteolysis in the ob/ob mice. • To explore potential mechanisms through which leptin affects osteolysis. • Dose-dependency • Target therapies to reduce local leptin

  16. Acknowledgements • Howard Hughes Medical Institute • Center of Healthy Aging Research, Oregon State University • Skeletal Biology Lab • Dr. Russell Turner • Dr. Urszula Iwaniec • Dawn Olson • Kenneth Philbrick • Kevin Ahern

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