Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Authors

  • L.J. Kidd,

    1. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
    2. School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia
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  • N.R. Cowling,

    1. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
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  • A.C.K. Wu,

    1. School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia
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  • W.L. Kelly,

    1. School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia
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  • M.R. Forwood

    Corresponding author
    1. School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia
    • School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia. T: +61 7 5552 7305; F: +61 7 5552 8908;
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Abstract

Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1827–1833, 2011

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