Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography.
OBJECTIVE
To non-invasively investigate the changes to epiphyseal bone occurring in a longitudinal pre-clinical model of osteoarthritis (OA) using in vivo micro-computed tomography (micro-CT).


METHODS
In vivo micro-CT images were acquired using a bench-top micro-CT scanner, which produces three-dimensional data with isotropic voxel spacing of 0.046 mm. Male rodents were scanned prior to surgical destabilization, consisting of anterior cruciate ligament transection and partial medial menisectomy (ACLX). Subsequent scans were performed every 4 weeks post-ACLX, for up to 5 months. Volumetric bone mineral density (vBMD) was measured in specific, anatomically segmented regions within each image. The ACLX rodent data were compared with the contralateral non-operated hind limb of the same animal, as well as a sham-operated group (SHAM) of animals, for each time point. End-point histology compared changes to cartilage and bone between the ACLX and control animals.


RESULTS
The micro-CT protocol produced sufficient spatial resolution and signal-to-noise ratio (SNR=19) to quantify subchondral bone pathology, with an acceptable entrance exposure to radiation (0.36 Gy). Significantly lower vBMD was measured in the ACLX group, vs SHAM rodents, at 1, 4, and 5 months post-surgery (P<0.05). Qualitative observations of ACLX joints revealed significant loss of cartilage, subchondral bone cysts, and calcification of tendon similar to changes found in humans.


CONCLUSIONS
This study demonstrates in vivo micro-CT as an effective method for investigating the development of rodent knee OA longitudinally. This method can be applied, in future pre-clinical trials, to non-destructively monitor the efficacy of pharmacological interventions.
McErlain
D D
DD
Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Canada. dmcerl@imaging.robarts.ca
Appleton
C T G
CT
Litchfield
R B
RB
Pitelka
V
V
Henry
J L
JL
Bernier
S M
SM
Beier
F
F
Holdsworth
D W
DW
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D001169:Arthritis, Experimental; D001845:Bone Cysts / Q000000981:diagnostic imaging / Q000473:pathology; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000473:pathology*; D018450:Disease Progression; D006132:Growth Plate / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008852:Microradiography / Q000379:methods*; D010003:Osteoarthritis / Q000000981:diagnostic imaging* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013264:Stifle; D014057:Tomography, X-Ray Computed / Q000379:methods