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Open Access Highly Accessed Research article

Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study

Joerg Arnoldi125*, Antoine Alves3 and Philip Procter14

Author Affiliations

1 Stryker Osteosynthesis, Selzach, Switzerland

2 Department of Biomaterials, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

3 Namsa-Biomatech, Chasse-sur-Rhone, France

4 School of Engineering & Design, Brunel University, Uxbridge, UK

5 Moraenenweg 6, 2544 Bettlach, Switzerland

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BMC Musculoskeletal Disorders 2014, 15:97  doi:10.1186/1471-2474-15-97

Published: 23 March 2014

Abstract

Background

In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site.

Methods

ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10.

Results

Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (pā€‰<ā€‰5%). In the ZOL group bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects.

Conclusion

This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature.

Keywords:
Screw; Osteointegration; Bisphosphonates; Zoledronic acid; Early bone repair; Cellular events