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Surface bound bisphosphonate for implant fixation in bone
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Läkemedel bundet till implantatytan förbättrar implantatets förankring i ben (Swedish)
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.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1059
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-15310ISBN: 978-91-7393-919-5 (print)OAI: oai:DiVA.org:liu-15310DiVA: diva2:113874
Public defence
2008-05-21, Elsa Brännströms sal, Campus US, Hälsouniversitetet, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2012-01-19Bibliographically approved
List of papers
1. Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion
Open this publication in new window or tab >>Surface-bound bisphosphonates enhance screw fixation in rats—increasing effect up to 8 weeks after insertion
2007 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, 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
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15306 (URN)10.1080/17453670710013979 (DOI)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
2. Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
Open this publication in new window or tab >>Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
2008 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 86A, no 1, 220-227 p.Article in journal (Refereed) Published
Abstract [en]

Recently published data indicate that immobilized N-bisphosphonate enhances the pullout force and energy uptake of implanted stainless steel screws at 2 weeks in rat tibia. This study compares titanium screws with and without a bisphosphonate coating in the same animal model. The screws were first coated with an 100-nm thick crosslinked fibrinogen film. Pamidronate was subsequently immobilized into this film via EDC/NHS-activated carboxyl groups within the fibrinogen matrix, and finally another N-bisphosphonate, ibandronate, was physically adsorbed. The release kinetics of immobilized 14C-alendronate was measured in buffer up to 724 h and showed a 60% release within 8 h. Mechanical tests demonstrated a 32% (p = 0.04) and 48% (p = 0.02) larger pullout force and energy until failure after 2 weeks of implantation, compared to uncoated titanium screws. A control study with physically adsorbed pamidronate showed no effect on mechanical fixation, probably due to a too small adsorbed amount. We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix-bound bisphosphonates.

Place, publisher, year, edition, pages
Hoboken, NJ, United States: John Wiley & Sons, 2008
Keyword
Bisphosphonate, pull-out, titanium, drug release, gamma sterilization, stainless steel, rat, fibrinogen, coating
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15307 (URN)10.1002/jbm.a.31583 (DOI)000256459500021 ()
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
3. Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats
Open this publication in new window or tab >>Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats
Show others...
2008 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 42, no 2, 365-371 p.Article in journal (Refereed) Published
Abstract [en]

Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen.

Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n = 33) and 8 (n = 27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 μm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n = 28).

At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 μm distance it was more than doubled. At 1 week, coated screws had less implant–bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.

Place, publisher, year, edition, pages
Elsevier/ScienceDirect, 2008
Keyword
Histomorphometry; Stainless steel; Torque removal; Bisphosphonate; Implant fixation
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15308 (URN)10.1016/j.bone.2007.10.013 (DOI)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2017-12-14Bibliographically approved
4. A bisphosphonate coating improves the bony fixation of stainless steel screws in ovariectomized rats
Open this publication in new window or tab >>A bisphosphonate coating improves the bony fixation of stainless steel screws in ovariectomized rats
2008 (English)Article in journal (Refereed) Submitted
Abstract [en]

Background: Bisphosphonate coatings improve the fixation of implants in bone. Stainless steels screws inserted in the rat tibia become encapsulated by new bone if they are coated with bisphosphonates in a crosslinked fibrinogen matrix. Thereby, the coating leads to a gradual increase in pull-out force. We now investigate if this bisphosphonate coating is capable to improve the mechanical fixation also in osteoporotic bone.

Methods: Stainless steel screws were coated with a thin crosslinked fibrinogen matrix. With EDC/NHS coupling technique, pamidronate was bound to carboxylic groups and ibandronate was adsorbed in the fibrinogen matrix. Uncoated stainless steel screws and bisphosphonatecoated screws were inserted bilaterally in the proximal tibia in 10 ovariectomized and 10 sham operated rats. At 2 weeks pull-out force and energy was measured.

Results: In the ovariectomized rats, pull-out force was 53 % higher for bisphosphonate coated screws compared to control screws. Energy was 44 % higher. The sham operated rats showed a higher variation, and no effect of the coating was found.

Conclusion: The coating was sufficient to improve fixation in ovariectomized rats

National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-15309 (URN)
Available from: 2008-10-30 Created: 2008-10-30 Last updated: 2009-08-21Bibliographically approved

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Wermelin, Karin

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