Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible.
OBJECTIVE
The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling.


METHODS
Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed.


RESULTS
Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham--this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group.


CONCLUSIONS
Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition.
Department of Anatomy and Cell Biology, University of Indianapolis, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
D J
DJ
Kubek
D B
DB
Burr
M R
MR
Allen
D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001857:Bone Matrix / Q000187:drug effects / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects; D004396:Coloring Agents; D003804:Dentin / Q000187:drug effects / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006253:Haversian System / Q000187:drug effects / Q000473:pathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008334:Mandible / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D010513:Periodontal Ligament / Q000187:drug effects / Q000473:pathology; D014677:Pharmaceutical Vehicles; D012394:Rosaniline Dyes; D014074:Tooth Calcification / Q000187:drug effects; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004396:Coloring Agents; D004164:Diphosphonates; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007093:Imidazoles; D014677:Pharmaceutical Vehicles; D012394:Rosaniline Dyes; C025485:basic fuchsin; D000077211:Zoledronic Acid; C007740:fluorexon