Do bisphosphonates inhibit direct fracture healing? a laboratory investigation using an animal model

T. Savaridas*, R. J. Wallace, D. M. Salter, A. H. R. W. Simpson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 mu g/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (SD 7.63) vs 24.65 Nmm(-2) (SD 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (SD 0.75) vs 4.6 mmAl (SD 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Original languageEnglish
Pages (from-to)1263-1268
Number of pages6
JournalThe Journal of Bone and Joint Surgery - British volume
Issue number9
Publication statusPublished - Sept 2013


  • suppressed bone turnover
  • alendronate therapy
  • intervention trial
  • zoledronic acid
  • long bones
  • repair
  • rats
  • osteoperosis
  • microdamage
  • increases


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