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Anti-RANKL treatment improves screw fixation in cancellous bone in rats
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
2015 (English)In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 46, no 6, 990-995 p.Article in journal (Refereed) Published
Abstract [en]

Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 mu g/kg/day), alendronate (200 mu g/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with mu CT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p less than 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p less than 0.001). This increase was higher than with any alendronate dose (p less than 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an antiRANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.

Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 46, no 6, 990-995 p.
Keyword [en]
Antiresorptives; Denosumab; Bisphosphonates; Rat model; Implant fixation; Fracture healing
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-119239DOI: 10.1016/j.injury.2015.02.011ISI: 000355018800009PubMedID: 25744169OAI: oai:DiVA.org:liu-119239DiVA: diva2:821258
Note

Funding Agencies|Swedish Research Council [2031-47-5]; AFA Insurance company; European Union 7th framework programme (FP7) [279239]; Linkoping University

Available from: 2015-06-15 Created: 2015-06-12 Last updated: 2015-06-15

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Bernhardsson, MagnusSandberg, OlofAspenberg, Per
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Division of Clinical SciencesFaculty of Medicine and Health SciencesDepartment of Orthopaedics in Linköping
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