Effects of risedronate on alveolar bone loss and angiogenesis: a stereologic study in rats.
BACKGROUND
The present study was designed to evaluate the effects of risedronate, one of the most potent bisphosphonates, on alveolar bone resorption and angiogenesis in rats with experimental periodontitis to identify dose-response curves and treatment durations that can be therapeutic for periodontal therapy versus those associated with osteonecrosis of the jaws.


METHODS
Thirty-five rats, 25 with experimental periodontitis (groups 1 through 5) and 10 with healthy periodontium (groups 6 and 7), were divided into seven equal groups: group 1 received no treatment; groups 2 and 3 received risedronate, 0.1 and 1 mg/kg, respectively, for 3 weeks; groups 4 and 5 received risedronate, 0.1 and 1 mg/kg, respectively, for 8 weeks; and groups 6 and 7 received 0.9% NaCl for 3 and 8 weeks, respectively. Animals in groups 2 through 7 were administered treatment 5 days per week. After histologic processing, histomorphometric and stereologic analyses were carried out to estimate the number of blood vessels (NBV) and the volumetric densities of bone (Vb), marrow (Vm), osteoblasts (Vob), and osteoclasts (Voc).


RESULTS
A total of 0.1 and 1 mg/kg risedronate for 3 weeks (groups 2 and 3) significantly increased Vb and Vob and decreased Vm more prominently in group 2 (P <0.001), whereas 1 mg/kg risedronate for 8 weeks (group 5) induced no significant improvement in these parameters compared to group 1 (P >0.05). No significant decrease in Voc was found in drug-administered groups compared to group 1 (P >0.05). A significant decrease in NBV (P <0.01) and positive correlation between NBV and Vb (r(2) = 0.941; P = 0.006) were found only in group 5.


CONCLUSIONS
A short duration of risedronate administration may be useful in inhibiting bone resorption in periodontitis, whereas excessive dosages of the drug administered in longer durations can lead to impairment of bone formation and angiogenesis.
Department of Periodontology, Ondokuzmayis University, Samsun, Turkey. ozkandt@hotmail.com
Burcu Ozkan
BO
Cetinkaya
Gonca Cayir
GC
Keles
Bulent
B
Ayas
Pinar
P
Gurgor
D016301:Alveolar Bone Loss / Q000188:drug therapy*; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007091:Image Processing, Computer-Assisted; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010020:Osteonecrosis / Q000139:chemically induced; D017622:Periodontal Attachment Loss / Q000188:drug therapy / Q000473:pathology; D010518:Periodontitis / Q000188:drug therapy / Q000473:pathology; D010519:Periodontium / Q000187:drug effects; D010919:Placebos; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid; D013997:Time Factors
D050071:Bone Density Conservation Agents; D010919:Placebos; D000068296:Risedronic Acid; D012968:Etidronic Acid