The use of live-animal micro-computed tomography to determine the effect of a novel phospholipase A2 inhibitor on alveolar bone loss in an in vivo mouse model of periodontitis.
OBJECTIVE
Live-animal micro-computed tomography is a new and promising technique that can be used to quantify changes in bone volume for periodontal disease models. The major aim of this study was to develop the methodology of live-animal micro-computed tomography and to determine the effect of a novel secretory phospholipase A2 inhibitor on alveolar bone loss.


METHODS
Periodontitis was induced in mice by oral infection with Porphyromonas gingivalis over a period of 13 wk, and live-animal micro-computed tomography scans were taken at different time-points to determine bone volume changes with disease progression. This enabled conclusions to be made as to when treatment was most likely to be effective. In addition, the model was used to investigate a novel drug, the secretory phospholipase A2 inhibitor, KHO64, and its potential ability to inhibit osteoclast bone resorption and treat periodontitis.


RESULTS
The results from live-animal micro-computed tomography scans revealed greater, statistically significant, bone volume loss in diseased mice compared with normal mice (p < 0.05). This corresponded to a larger area from the cemento-enamel junction to the alveolar bone crest, as assessed by stereo imaging (p < 0.001). These techniques can therefore detect and quantify alveolar bone loss. Both methods revealed that KHO64 had no significant effect on the volume of bone resorption.


CONCLUSIONS
Live-animal micro-computed tomography is a robust, reproducible technique that clearly demonstrates significant time-dependent changes in alveolar bone volume in a small-animal model of periodontitis.
Cantley
M D
MD
Discipline of Pathology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Bartold
P M
PM
Marino
V
V
Reid
R C
RC
Fairlie
D P
DP
Wyszynski
R N
RN
Zilm
P S
PS
Haynes
D R
DR
D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D001442:Bacteroides Infections / Q000201:enzymology*; D015519:Bone Density; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000187:drug effects; D010421:Pentanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D010518:Periodontitis / Q000201:enzymology* / Q000382:microbiology / Q000517:prevention & control; D064801:Phospholipase A2 Inhibitors; D016966:Porphyromonas gingivalis; D019237:Tooth Cervix / Q000000981:diagnostic imaging; D055114:X-Ray Microtomography / Q000379:methods*
C503211:5-(4-benzyloxyphenyl)-4S-(7-phenylheptanoylamino)pentanoic acid; D004791:Enzyme Inhibitors; D010421:Pentanoic Acids; D064801:Phospholipase A2 Inhibitors