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Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
2007 (English)In: Acta Orthopaedica, ISSN 1745-3674, Vol. 78, no 3, 385-392 p.Article in journal (Refereed) Published
Abstract [en]

Background: A bisphosphonate coating improves screw fixation 2 weeks after implantation in cancellous bone. This study on rats examined further development of fixation over time for screws inserted in cancellous and cortical bone.

Methods: SS screws were coated with a multiple layer of fibrinogen. Half of the screws were coated further with bisphosphonates, which were linked to the fibrinogen. The screws were inserted in cancellous and cortical bone in rats. The rats were killed after 5 h, 4 days, 1, 2, 4, 8, and 24 weeks, and fixation was evaluated by pullout test.

Results: There was a gradual increase in pull-out force over time in both cancellous and cortical bone. The bisphosphonate coating improved fixation. Moreover, the difference between the bisphosphonate and control groups increased with time. The pull-out force was almost twice that of the controls for screws inserted in cancellous bone at 8 weeks. Energy uptake was increased more than 3-fold.

Discussion: The energy uptake and pull-out force of a screw depends on the bone engaged with the threads. Thus, the presence of bisphosphonates increased the amount or quality of this bone by affecting the resorp-tion/formation in a positive way. The increased effect of the bisphosphonates with time thus suggests that bisphosphonate is retained within the remodeling bone, with a positive effect on its gradual adaptation to the implant.

Place, publisher, year, edition, pages
Talyor & Francis , 2007. Vol. 78, no 3, 385-392 p.
National Category
URN: urn:nbn:se:liu:diva-15306DOI: 10.1080/17453670710013979OAI: diva2:113865
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2009-08-21Bibliographically approved
In thesis
1. Surface bound bisphosphonate for implant fixation in bone
Open this publication in new window or tab >>Surface bound bisphosphonate for implant fixation in bone
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Läkemedel bundet till implantatytan förbättrar implantatets förankring i ben
Abstract [en]

During the surgical preparation of bone, prior to insertion of an implant, bone will be traumatized which leads to local resorption. Consequently, early implant fixation might be reduced. Impaired early fixation, as evidenced by radiostereometry, has been associated with increased risk of late loosening. Bisphosphonates are known to inhibit bone resorption by osteoclasts and have shown to increase implant fixation when administered systemically or locally directly at the bone prior to implant insertion.

A method to bind bisphosphonates directly to the implant was developed. Stainless steel screws were coated with crosslinked fibrinogen, serving as an anchor for bisphosphonate attachment. The screws were inserted in the tibial metaphysis in rats and implant fixation was analyzed with pullout measurements. Bisphosphonate coated screws turned out to have 28 % higher pullout force at 2 weeks compared to control screws with the fibrinogen coating only. The next experiment was designed to measure at what stage in the healing process the strongest bisphosphonate effect was gained. Bisphosphonate coated screws were expected to reduce the resorption of the traumatized bone. However, no decreased fixation was found in the control group. Instead, the fixation increased with time, and so did the effect of the bisphosphonates. At 8 weeks, the pullout force was twice as high for screws with bisphosphonate compared to control screws. By histology at 8 weeks, a bone envelope was found around bisphosphonate coated screws but absent around control screws. Thus, the anti catabolic action of the bisphosphonate resulted in an increased amount of bone surrounding the bisphosphonate screws.

Titanium is generally considered to be better fixated in bone compared to stainless steel. The coating technique was found to be applicable on titanium as well, again with improved fixation.

A majority of fractures occur in osteoporotic bone. Despite the relatively low amount of bisphosphonates at the screws, the bisphosphonate coating improved implant fixation at 2 weeks also in rats made osteoporotic by ovariectomy.

In conclusion, bisphosphonates bound to titanium or stainless steel screws coated with fibrinogen increased fixation in bone, in rats. These results suggest that the bisphosphonate and fibrinogen coating might improve the fixation of screw shaped implants and possibly also arthroplasties, in humans.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 49 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1059
National Category
urn:nbn:se:liu:diva-15310 (URN)978-91-7393-919-5 (ISBN)
Public defence
2008-05-21, Elsa Brännströms sal, Campus US, Hälsouniversitetet, Linköpings universitet, Linköping, 13:00 (English)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2012-01-19Bibliographically approved

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Wermelin, KarinTengvall, PenttiAspenberg, Per
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Orthopaedics and Sports Medicine Faculty of Health SciencesApplied Physics The Institute of TechnologyDepartment of Orthopaedics Linköping
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