Detecting Particle-Induced Osteolysis by Micro-CT Analysis

Student: Bailey LindenmaierMentors: Dr. Russell Turner & Dr. Urszula Iwaniec

Skeletal Biology Lab

OverviewRelevance of particle-induced osteolysisObesity and factors that contribute to increased risk of

osteolysisAnimal model for particle-induced osteolysisAimsResults and conclusions

Prosthetic Joint ReplacementApproximately 600,000 joint (hip or knee) replacements

are performed annuallyConditions 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

Particle-Induced Osteolysis

August 22, 2011“Hip Implant Complaints Surge, Even asthe 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 Isn’t Always Improved”By BARRY MEIER

May 10, 2011“Hip Makers Told to Study More Data”By BARRY MEIER

ObesityBMI > 30 kg/m2

Excess body fat

Obesity is associated with: Increased joint

replacement Increased failure rates

Normal Overweight

Obese

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?AdipokinePleiotropic hormone

vs.

Model of Obesity: ob/ob MiceLeptin Deficient

Giving back leptin corrects for phenotypic abnormalities

Hyperphagic

Rapidly become obese by four weeks of age

Aim1)Verify results obtained

by von KnochLeptin-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

Study Design4 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

Group Treatment1 WT2 WT + Particle3 ob/ob4 ob/ob + Particle

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

WT + Particles

ob/ob + Particles

WT ob/ob

Micro-CT Imaging of Parietal Bone

Group 1 Group 2 Group 3 Group 4

0 4 10

ob/obWTSeries1

0

1

2

3

4

No-Treat-mentParticles

Calv

ari

al O

steoly

tic

Sco

re(Severe)

(None))

Two-way ANOVAGenotype (P = 0.028)Treatment (P < 0.001)

Genotype x Treatment (P = 0.028)

*

*

* P < 0.01 within genotype

Osteolytic Score of Particle-Induced Osteolysis

ConclusionsMicro-computed tomography is an effective method

to identify and measure osteolysis

ob/ob mice experience less particle-induced osteolysis than WT miceLack of leptin signaling?Up regulated inflammatory cytokines?

On the HorizonLab 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-dependencyTarget therapies to reduce local leptin

AcknowledgementsHoward Hughes Medical InstituteCenter of Healthy Aging Research, Oregon State

UniversitySkeletal Biology Lab

Dr. Russell TurnerDr. Urszula IwaniecDawn Olson Kenneth Philbrick

Kevin Ahern