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Open Access Highly Accessed Research article

Influence of Statins locally applied from orthopedic implants on osseous integration

Stephan Pauly1*, David A Back13, Kathrin Kaeppler14, Norbert P Haas1, Gerhard Schmidmaier4 and Britt Wildemann12

Author Affiliations

1 Julius Wolff Institut, Center for Musculoskeletal Surgery, Charité Universitaetsmedizin Berlin, Berlin, Germany

2 Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitaetsmedizin Berlin, Berlin, Germany

3 Department of Orthopedics and Traumatology, German Armed Forces Hospital Berlin, Berlin, Germany

4 Department of Orthopedic and Trauma Surgery, University of Heidelberg, Heidelberg, Germany

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BMC Musculoskeletal Disorders 2012, 13:208  doi:10.1186/1471-2474-13-208

Published: 26 October 2012

Abstract

Background

Simvastatin increases the expression of bone morphogenetic protein 2 (BMP-2) in osteoblasts, therefore it is important to investigate the influence of statins on bone formation, fracture healing and implant integration. The aim of the present study was to investigate the effect of Simvastatin, locally applied from intramedullary coated and bioactive implants, on bone integration using biomechanical and histomorphometrical analyses.

Methods

Eighty rats received retrograde nailing of the femur with titanium implants: uncoated vs. polymer-only (poly(D,L-lactide)) vs. polymer plus drug coated (either Simvastatin low- or high dosed; “SIM low/ high”). Femurs were harvested after 56 days for radiographic and histomorphometric or biomechanical analysis (push-out).

Results

Radiographic analysis revealed no pathological findings for animals of the control and SIM low dose group. However, n=2/10 animals of the SIM high group showed osteolysis next to the implant without evidence of bacterial infection determined by microbiological analysis. Biomechanical results showed a significant decrease in fixation strength for SIM high coated implants vs. the control groups (uncoated and PDLLA). Histomorphometry revealed a significantly reduced total as well as direct bone/implant contact for SIM high- implants vs. controls (uncoated and PDLLA-groups). Total contact was reduced for SIM low vs. uncoated controls. Significantly reduced new bone formation was measured around SIM high coated implants vs. both control groups.

Conclusions

This animal study suggests impaired implant integration with local application of Simvastatin from intramedullary titanium implants after 8 weeks when compared to uncoated or carrier-only coated controls.

Keywords:
Statins; Simvastatin; Implant integration; BMP; Local application