student: bailey lindenmaier mentors: dr. russell turner & dr. urszula iwaniec skeletal biology...
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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