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A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
Gothenburg University.
Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
2012 (Engelska)Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr 5, s. 1148-1151Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

Ort, förlag, år, upplaga, sidor
Elsevier , 2012. Vol. 50, nr 5, s. 1148-1151
Nyckelord [en]
Bone healing, Dental implant, Drug delivery, Mechanical test, Osseointegration bisphosphonates
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-77527DOI: 10.1016/j.bone.2012.02.001ISI: 000303274400018OAI: oai:DiVA.org:liu-77527DiVA, id: diva2:528606
Anmärkning

Funding Agencies|Swedish Research Council|VR 2009-6725|

Tillgänglig från: 2012-05-28 Skapad: 2012-05-22 Senast uppdaterad: 2017-12-07
Ingår i avhandling
1. Bisphosphonates and implants in the jaw bone
Öppna denna publikation i ny flik eller fönster >>Bisphosphonates and implants in the jaw bone
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.

The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?

In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.

In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2013. s. 144
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1348
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-89669 (URN)978-91-7519-724-1 (ISBN)
Disputation
2013-03-22, Berzeliussalen, hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2013-03-01 Skapad: 2013-03-01 Senast uppdaterad: 2016-09-07Bibliografiskt granskad

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