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Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening
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.
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
2011 (English)In: BONE, ISSN 8756-3282, Vol. 48, no 2, 225-230 p.Article in journal (Refereed) Published
Abstract [en]

Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 mu g /kg/day), an extreme dose of alendronate (200 mu g/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2011. Vol. 48, no 2, 225-230 p.
Keyword [en]
RANKL, Bisphosphonates, Resorption, Implant, Loosening, Instability
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-65956DOI: 10.1016/j.bone.2010.09.024ISI: 000286543700008OAI: oai:DiVA.org:liu-65956DiVA: diva2:400663
Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2012-02-14

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Aspenberg, PerAgholme, FredrikFahlgren, AnnaMagnusson, Per
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Orthopaedics and Sports MedicineFaculty of Health SciencesDepartment of Orthopaedics LinköpingDepartment of Clinical and Experimental MedicineClinical ChemistryDepartment of Clinical Chemistry
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