High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model.
The effect of alendronate on osteoclast and osteoblast function was studied in a novel spine pseudarthrosis model in rats. Sixty-three Sprague-Dawley rats were divided into three groups: control group (saline), therapeutic dose group (1 microg/kg/week), and one-log overdose group (10 microg/kg/week). Animals had L4-L5 posterior intertransverse process fusion with limited bone graft and were sacrificed at 2, 4, and 6 weeks. Manual palpation showed no notable differences among groups. Treatment group radiographic scores were equal to or better than control group scores and were higher than the overdose group at 2 and 6 weeks. Qualitatively, limited histologic remodeling and poor osteoclastic and osteoblastic function were noted in the alendronate treated groups. Quantitative histologic analysis showed fewer osteoclasts in the therapeutic and high-dose groups (p < 0.001). The percent osteoblasts per bone surface area was lower in the high-dose group (p < 0.05). The results suggest that the effect of alendronate was dose dependent and animal model dependent and that supranormal doses of alendronate had a deleterious effect on osteoclastic and osteoblastic function in this model.
Sama
Andrew A
AA
Facility for Comparative Research, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. samaa@hss.edu
Khan
Safdar N
SN
Myers
Elizabeth R
ER
Huang
Russel C
RC
Cammisa
Frank P
FP
Sandhu
Harvinder S
HS
Lane
Joseph M
JM
D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D011542:Pseudarthrosis / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
D019386:Alendronate