High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model

Clin Orthop Relat Res. 2004 Aug;(425):135-42. doi: 10.1097/00003086-200408000-00018.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alendronate / administration & dosage
  • Alendronate / pharmacology*
  • Analysis of Variance
  • Animals
  • Chi-Square Distribution
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Lumbar Vertebrae / surgery
  • Male
  • Osteoblasts / drug effects*
  • Osteoclasts / drug effects*
  • Pseudarthrosis / surgery
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing / drug effects


  • Alendronate