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Effect of locally administered zoledronic acid on injury-induced intramembranous bone regeneration and osseointegration of a titanium implant in rats
Authors:Simo S. A. Miettinen  Jarkko Jaatinen  Alpo Pelttari  Reijo Lappalainen  Jukka Mönkkönen  Petri K. Venesmaa  Heikki P. J. Kröger
Affiliation:(1) Department of Physical Medicine and Rehabilitation, Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA;(2) National Rehabilitation Hospital, 102 Irving Street NW, Washington, DC 20010, USA;(3) Department of Radiology, Johns Hopkins University Outpatient Center, 601 North Caroline Street, Suite 4233, Baltimore, MD 21287, USA;(4) Catholic University of America, 2344 Nebraska Avenue NW, Washington, DC 20016, USA;(5) Novartis Pharmaceuticals, Inc., One Health Plaza, Building 122, East Hanover, NJ 07936, USA
Abstract:Background  Intramedullary implantation causes injury-induced stimulation of intramembranous bone regeneration. Intramedullary bone injury along with stress shielding may induce periimplant bone loss and cause early aseptic loosening of an implant. The aim of this study was to determine the effect of locally administered zoledronic acid on periimplant bone and injury-induced stimulation of intramembranous bone regeneration in a rat model. Methods  A total of 28 male rats had a titanium implant inserted into their right femur. During the operation, the medullary canal was lavaged using 20 μM zoledronic acid (Zometa 4 mg/5 ml) or sodium chloride. Follow-up times were 4 and 12 weeks, with each follow-up group consisting of seven rats. The femurs with the titanium implants in situ were harvested, and three microscope sections were cut from each femur. The sections were photographed and analyzed with the Analysis computer program. Results  Between 4 and 12 weeks, the length of fluorescence bone contact increased significantly in both groups (control 15.7% SD and zoledronic acid 18.8% SD), although the difference between the groups was not significant. Periimplant bone volume (thickness) was increased in the 4-week zoledronic acid group compared to the controls (±13.4%, P = 0.002) but at 12 weeks the groups no longer differed from each other. Conclusions  Our results suggest that zoledronic acid may prevent injury-induced bone loss near an intramedullary implant by inhibiting bone resorption shortly after implantation. This may provide better periimplant bone stock during the early postoperative period.
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