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Student: Bailey Lindenmaier Mentors: Dr. Russell Turner & Dr. Urszula Iwaniec Skeletal Biology Lab.

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Presentation on theme: "Student: Bailey Lindenmaier Mentors: Dr. Russell Turner & Dr. Urszula Iwaniec Skeletal Biology Lab."— Presentation transcript:

1 Student: Bailey Lindenmaier Mentors: Dr. Russell Turner & Dr. Urszula Iwaniec 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 August 22, 2011 Hip Implant Complaints Surge, Even as the Dangers Are Studied By BARRY MEIER and JANET ROBERTS March 3, 2010 Concerns Over Metal on Metal Hip Implants By BARRY MEIER June 25, 2011 In Medicine, New Isnt Always Improved By BARRY MEIER May 10, 2011 Hip Makers Told to Study More Data By BARRY MEIER

6 Obesity BMI > 30 kg/m 2 Excess body fat Obesity is associated with: Increased joint replacement Increased failure rates NormalOverweightObese

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): 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 GroupTreatment 1WT 2WT + Particle 3ob/ob 4ob/ob + Particle

12 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

13 WT + Particles ob/ob + Particles WT ob/ob Micro-CT Imaging of Parietal Bone Group 1Group 2Group 3Group

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

15 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?

16 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

17 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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