Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis

Knoch, Fabian von; Wedemeyer, Christian; Heckelei, Anja; Saxler, Guido; Hilken, Gero; Brankamp, Jochen; Sterner, Thomas; Landgraeber, Stefan; Henschke, F.; Löer, F.; Knoch, Marius von

doi:10.1016/j.biomaterials.2005.02.008

Cited by 43 publications

(28 citation statements)

References 36 publications

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“…The minimally loaded intramedullary implantation model, in male rabbits only, was chosen because the effect of the drug could be isolated from confounding factors, such as implant design, loading conditions and hormonal factors. Since orally administered statins are subject to hepatic first-pass metabolism, the bioavailability of statins to bone sites may be impaired, alkali hydrolysis and parenteral administration of simvastatin was preferred in our study [25]. The blood chemistry obtained before and after the study revealed a significant (p<0.05) decrease in cholesterol levels, which was in concordance with an active compound in the circulation lowering the blood lipid levels.…”

Section: Discussionmentioning

confidence: 48%

“…Statins have been shown to activate the promoter of the bone morphogenetic protein-2 (BMP-2) gene in osteoblasts and decrease the number of osteoclasts in vitro [17,18]. BMP-2 is one of the most potent osteoconductive proteins involved in the recruitment, proliferation and differentiation of osteoprogenitor cells, resulting in bone formation [25]. Simvastatin also increases cancellous bone volume, bone formation rate (BFR) and cancellous bone compressive strength in vivo [16].…”

Section: Discussionmentioning

confidence: 99%

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Osseointegration in arthroplasty: can simvastatin promote bone response to implants?

Başarır

Erdemli

Can

et al. 2007

International Orthopaedics (SICOT)

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Cementless fixation depends on bone ingrowth for long-term success. Simvastatin as a lipid lowering agent has been demonstrated to have osteoanabolic effects. This study was designed to measure the possible effect of simvastatin on implant osseointegration. Bilateral femoral implantation of titanium cylinders was performed in 20 rabbits. Blood lipid levels were measured pre-and postoperatively. Scanning electron microscopy (SEM) was used to measure the percentage of the surface of each implant in contact with bone and mechanical pull-out testing was performed. The blood lipid levels were significantly reduced in the simvastatin group. Histomorphometric examination revealed increased bone ingrowth and mechanical examination showed increased interface strength in the simvastatin group. Mechanical and histological data showed superior stability and osseous adaptation at the bone/ implant interface for the simvastatin group. We conclude that simvastatin has potential as a means of enhancing bone ingrowth, which is a key factor in the longevity of cementless implants.Résumé La fixation d'une prothèse sans ciment dépend de la réhabitation osseuse. La Simvastatine est un agent lipidique qui a un effet ostéo anabolique. Cette étude a pour but de montrer les effets de la Simvastatine sur l'ostéo intégration osseuse. Matériel et méthode : une implantation de cylindres de titane a été réalisée sur les deux fémurs de vingt lapins. Le taux de lipide a été mesuré en pré et post opératoire. L'examen en microscopique électronique a mesuré le pourcentage de la surface de réhabitation et des essais d'arrachage ont également été réalisés. Résultats : le niveau des lipides sanguins est réduit de façon significative dans le groupe de Simvastatine. L'histomorphométrie osseuse montre la croissance, l'orientation de la réhabitation et les tests mécaniques, l'augmentation de l'interface avec augmentation des forces nécessaires pour l'arrachage. En conclusion, les données mécaniques et histologiques montrent une stabilité supérieure dans le groupe Simvastatine. Nous pouvons conclure que la Simvastatine a un potentiel d'augmentation de la réhabitation osseuse facteur clé du succès à long terme des implants sans ciment.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Osseointegration in arthroplasty: can simvastatin promote bone response to implants?

Başarır

Erdemli

Can

et al. 2007

International Orthopaedics (SICOT)

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“…In contrast to protein-based biologics, organic compounds, known as small-molecule drugs, were identified by review of current clinical trials as agents to intercede in common pathways for bone loss or formation [8,52]. The most prominent agents include the two forms of bisphosphonates, either nitrogen-containing or simple [37].…”

Section: Search Strategy and Criteriamentioning

confidence: 99%

“…With respect to animal models, the addition of particles to rats and rabbits represented studies that examine biologic effects on cortical bone challenged with different types of particles [52]. In the rat model, osteolysis was induced when titanium pins were implanted in the femoral canal with UHMWPE particles.…”

Section: Search Strategy and Criteriamentioning

confidence: 99%

Are Biologic Treatments a Potential Approach to Wear- and Corrosion-related Problems?

Smith

Schwarz

2014

Clin Orthop Relat Res

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Where Are We Now? Biological treatments, defined as any nonsurgical intervention whose primary mechanism of action is reducing the host response to wear and/or corrosion products, have long been postulated as solutions for osteolysis and aseptic loosening of total joint arthroplasties. Despite extensive research on drugs that target the inflammatory, osteoclastic, and osteogenic responses to wear debris, no biological treatment has emerged as an approved therapy. We review the extensive preclinical research and modest clinical research to date, which has led to the central conclusion that the osteoclast is the primary target. We also allude to the significant changes in health care, unabated safety concerns about chronic immunosuppressive/antiinflammatory therapies, industry's complete lack of interest in developing an intervention for this condition, and the practical issues that have narrowly focused the possibilities for a biologic treatment for wear debris-induced osteolysis. Where Do We Need to Go? Based on the conclusions from research, and the economic, regulatory, and practical issues that limit the future directions toward the development of a biologic treatment, there are a few rational approaches that warrant investigation. These largely focus on FDA-approved osteoporosis therapies that target the osteoclast (bisphosphonates and anti-RANK ligand) and recombinant parathyroid hormone (teriparatide) prophylactic treatment to increase osseous integration of the prosthesis to overcome high-risk susceptibility to aseptic loosening. The other roadblock that must be overcome if there is to be an approved biologic therapy to prevent the progression of periprosthetic osteolysis and aseptic loosening is the development of radiological measures that can quantify a significant drug effect in a randomized, placebocontrolled clinical trial. We review the progress of volumetric quantification of osteolysis in animal studies and clinical pilots. How Do We Get There? Accepting the aforementioned rigid boundaries, we describe the emergence of repurposing FDA-approved drugs for new indications and public (National Institutes of Health, FDA, Centers for Disease Control and Prevention) and private (universities and drug and device manufactures) partnerships as the future roadmap for clinical translation. In the case of biologic treatments for wear debris-induced osteolysis, this will

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“…This indicated that statins may improve osseosintegration of titanium implants. Moreover, experimental studies have described positive effects of statins on conditions mimicking the course of aseptic loosening of orthopaedic implants (von Knoch et al, 2005a, Laing et al, 2008.…”

Section: Study I: Statinsmentioning

confidence: 99%

Use of medications and risk of revision after primary total hip arthroplasty

Thillemann¹

2009

Acta Orthopaedica

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Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis

Cited by 43 publications

References 36 publications

Osseointegration in arthroplasty: can simvastatin promote bone response to implants?

Osseointegration in arthroplasty: can simvastatin promote bone response to implants?

Are Biologic Treatments a Potential Approach to Wear- and Corrosion-related Problems?

Use of medications and risk of revision after primary total hip arthroplasty

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