Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis

Little, D. G., Smith, N. C., Williams, P. R., Briody, JN, Bilston, L. E., Smith, E. J., Gardiner, E. M. and Cowell, C. T. (2003) Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis. Journal of Bone And Mineral Research, 18 7: 1300-1307. doi:10.1359/jbmr.2003.18.7.1300

Author Little, D. G.
Smith, N. C.
Williams, P. R.
Briody, JN
Bilston, L. E.
Smith, E. J.
Gardiner, E. M.
Cowell, C. T.
Title Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis
Journal name Journal of Bone And Mineral Research   Check publisher's open access policy
ISSN 0884-0431
Publication date 2003-07
Sub-type Article (original research)
DOI 10.1359/jbmr.2003.18.7.1300
Volume 18
Issue 7
Start page 1300
End page 1307
Total pages 8
Place of publication Washington
Publisher Amer Soc Bone & Mineral Res
Language eng
Subject 11 Medical and Health Sciences
Abstract Prolonged healing times and stress-shielding osteopenia remain problematic in distraction osteogenesis. In this study of 30 rabbits, zoledronic acid increased regenerate volume, mineralization, and tibial strength and prevented osteopenia over a 6-week period. Translation to the clinical setting, if safe, could improve outcomes in distraction osteogenesis in children. Introduction: Because the external fixators for limb lengthening and reconstruction are designed to control the positions of bone fragments accurately, they also produce stress-shielding effects on the forming regenerate and surrounding bone. Osteopenia, leading to refracture and limitations on rehabilitation, are common consequences, potentially increasing morbidity and detracting from final clinical outcome. Materials and Methods: We examined the effect of zoledronic acid on distraction osteogenesis in 42 immature male NZW rabbits. The model chosen results in reliable regenerate formation and stress-shielding osteopenia. Fourteen animals received either Saline, zoledronic acid 0.1 mg/kg at surgery (ZOL), or another dose 2 weeks postoperatively (Redosed ZOL). Rabbits underwent DXA for bone mineral content and bone mineral density in regenerate and surrounding segments of operated and contralateral tibias. After death at 6 weeks, 30 pairs of tibias underwent quantitative computerized tomography (QCT) and four-point bend testing, and 12 were examined by histomorphometry. The study was powered at 0.8 to show differences of 1.3 SDs for mineral and mechanical parameters. Results: Osteopenia observed in tibias of the Saline group was absent in ZOL and Redosed ZOL tibias, the latter exhibiting higher bone mineral density and bone mineral content over contralateral regions (p < 0.01). Regenerate bone mineral content was higher in ZOL and Redosed ZOL versus Saline groups at 4 and 6 weeks (p < 0.01). Cross-sectional area was 49% and 59% greater at 6 weeks in ZOL and Redosed ZOL regenerates compared with the Saline group (p < 0.01). ZOL and Redosed ZOL tibias were 29% and 89% stronger by four-point bending than the Saline group (p < 0.01). Histomorphometry in the regenerate of ZOL and Redosed ZOL groups revealed higher trabecular bone volume and trabecular number compared with the Saline group (P < 0.001). Conclusions: Zoledronic acid administration led to significantly greater bone area, mineral content, strength, and trabecular number with reduced stress-shielding osteopenia in this model of distraction osteogenesis. These data suggest that intraoperative and postoperative zoledronic acid administration could improve outcomes in children undergoing limb lengthening.
Keyword Endocrinology & Metabolism
distraction osteogenesis
fracture healing
bone mineral density
X-ray Absorptiometry
Bisphosphonate Incadronate
Intramedullary Nail
Mineral Density
Ilizarov Method
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 65 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 25 Jan 2008, 15:57:29 EST