What potential biologic treatments are available for osteolysis?

Schwarz, Edward M.

doi:10.5435/00124635-200800001-00015

Cited by 37 publications

(34 citation statements)

References 18 publications

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“…Although weight loss and activity restriction may theoretically slow down the wear rate, these options have proved to be impractical. To date, no biological approaches to curtailing the chronic inflammatory reaction associated with wear particles have proved successful clinically, owing to the plethora of inflammatory mediators that are upregulated by particles, redundancy of inflammatory pathways and potential adverse effects of systemic treatments [20,21].…”

Section: Introductionmentioning

confidence: 99%

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Goodman

Gibon

Pajarinen

et al. 2014

J. R. Soc. Interface.

120

148

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ReviewCite this article: Goodman SB et al. 2014 Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. J. R. Soc. Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 ( pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-kB) by delivery of an NF-kB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

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Section: Introductionmentioning

confidence: 99%

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Goodman

Gibon

Pajarinen

et al. 2014

J. R. Soc. Interface.

120

148

View full text Add to dashboard Cite

show abstract

“…13 Also, TNFa antagonists have displayed promise in the setting of rheumatoid arthritis (RA) and psoriatic arthritis, suggesting that they may be a potential therapeutic option. 14,66,77 Similarly, due to its osteoclast mitigating properties, OPG has been targeted as feasible pharmacologic compound to pursue further investigation. 14,77 Another experimental compound which may prove beneficial in the therapeutic treatment of periprosthetic osteolysis is AM630, a selective antagonist of cannabinoid receptor 2 (CB2)-a principal modulator in bone remodeling-which has demonstrated success in inhibiting IL-1b and TNFa expression.…”

Section: Medicationsmentioning

confidence: 99%

“…14,66,77 Similarly, due to its osteoclast mitigating properties, OPG has been targeted as feasible pharmacologic compound to pursue further investigation. 14,77 Another experimental compound which may prove beneficial in the therapeutic treatment of periprosthetic osteolysis is AM630, a selective antagonist of cannabinoid receptor 2 (CB2)-a principal modulator in bone remodeling-which has demonstrated success in inhibiting IL-1b and TNFa expression. 15 Ren et al 78,79 has also explored the use of VEGF inhibiting agents in a mouse model and have shown a decrease in bone resorption suggesting a potential clinical role of these agents.…”

Section: Medicationsmentioning

confidence: 99%

Review of periprosthetic osteolysis in total joint arthroplasty: An emphasis on host factors and future directions

Beck

Illingworth

Saleh

2011

Journal Orthopaedic Research

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Periprosthetic osteolysis is one of the leading causes of total joint revision procedures. If allowed to progress in the absence of radiographic diagnosis and/or proper medical treatment, osteolysis may result in aseptic loosening yielding failure of the implant and the need for complex revision arthroplasty. The purpose of this review was to assess the current understanding of periprosthetic osteolysis with an emphasis on host factors and future directions. A PubMed search was conducted using the following key words; osteolysis, periprosthetic osteolysis, osteolysis imaging. Pertinent articles, as it pertained to the outline of the review, were selected. Periprosthetic osteolysis stems from numerous risk factors. Osteolysis host characteristic risk factors include gender, body weight, and genetics. Current implant designs have reduced the incidence of this disease; however no current design has been able to replicate the in vivo characteristics and therefore development of wear particles continues to be seen. Advanced methods of imaging diagnosis are on the rise, however early imaging diagnosis is currently ineffective. Pharmacologic intervention appears to be a logical avenue for medical intervention, but no approved drug therapy to prevent or inhibit periprosthetic osteolysis is currently available. Although the rate of periprosthetic osteolysis seems to be decreasing with advances in implant design and increased knowledge of the biological process of wear particle induced osteolysis, the rapid increase in the total number of total joint arthroplasties over the next two decades means that better ways of detecting and treating periprosthetic osteolysis are greatly needed. ß

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“…Both samples were incubated in a 37°C water bath for various time periods. A fraction of samples (100 µL) was collected at different time points (0, 3,5,7,9,12,14,16,18, and 20 hours). These samples were filtered through syringe filters (Minisart, Sartorius Stedim North America Inc, Bohemia, NY) with a pore size of 0.45 µm.…”

Section: Stability Of Cd-emmentioning

confidence: 99%

Cyclodextrin-erythromycin complexes as a drug delivery device for orthopedic application

Ren¹

2011

IJN

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Background Erythromycin, a hydrophobic antibiotic used to treat infectious diseases, is now gaining attention because of its anti-inflammatory effects and ability to inhibit osteoclasts formation. The aim of this study was to explore a cyclodextrin-erythromycin (CD-EM) complex for sustained treatment of orthopedic inflammation. Methods and results Erythromycin was reacted with β-cyclodextrin to form a nonhost-guest CD-EM complex using both kneading and stirring approaches. Physiochemical measurement data indicated that erythromycin and cyclodextrin formed a packing complex driven by intermolecular forces instead of a host-guest structure due to the limited space in the inner cavity of β-cyclodextrin. The CD-EM complex improved the stability of erythromycin in aqueous solution and had a longer duration of bactericidal activity than free erythromycin. Cytotoxicity and cell differentiation were evaluated in both murine MC3T3 preosteoblast cells and RAW 264.7 murine macrophage cells. The CD-EM complex was noncytotoxic and showed significant inhibition of osteoclast formation but had little effect on osteoblast viability and differentiation. Conclusion These attributes are especially important for the delivery of an adequate amount of erythromycin to the site of periprosthetic inflammation and reducing local inflammation in a sustained manner.

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What potential biologic treatments are available for osteolysis?

Cited by 37 publications

References 18 publications

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Review of periprosthetic osteolysis in total joint arthroplasty: An emphasis on host factors and future directions

Cyclodextrin-erythromycin complexes as a drug delivery device for orthopedic application

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