1. Detecting Particle-Induced Osteolysis by Micro-CT Analysis
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
Title: particle induced osteolysis

5. “Concerns Over ‘Metal on Metal’ Hip Implants”
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
FDA has said that there is a major concern and that joint replacements need to be reevaluated
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
Amenoric women and ob/ob mice with leptin = increase in osteocalcin which means bone formation

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.
Amenoric women and ob/ob mice with leptin = increase in osteocalcin which means bone formation

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. Histological section of a mouse calvaria experiencing osteolysis
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”
Leptin enhances production of bone and immune regulatory cytokines pathological bone resorption
Histological section of a mouse calvaria experiencing osteolysis
2)Micro-computed tomography is a viable method to rapidly quantify particle- induced osteolysis in three dimensions

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, hr light/dark cycle, singly housed
Electron microscope of polyethylene particles

11. Group
Treatment 1 WT 2
WT + Particle 3
ob/ob 4
ob/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. Micro-CT Imaging of Parietal Bone4 1
WT + Particles
ob/ob + Particles WT
ob/ob
Group 1
Group 2
Group 3
Group 4

14. Osteolytic Score of Particle-Induced Osteolysis
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

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