Low-Intensity Pulsed Ultrasound (LIPUS) May Prevent Polyethylene Induced Periprosthetic Osteolysis In Vivo

Zhao, Xiang; Cai, Xun-Zi; Shi, Zhijun; Zhu, Fengzhao; Zhao, Gang-Sheng; Yan, Shigui

doi:10.1016/j.ultrasmedbio.2011.11.005

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…Our previous study found that 200 mW/cm 2 for 20 minutes per day effectively prevented periprosthetic osteolysis in the medullary canal of the rabbit femur [43]. In this study, rabbits were treated with a 1-MHz pulse frequency, 20% duty cycle, and 100-Hz repetition rate at an average intensity of 200 mW/cm 2 20 minutes per day for 12 weeks.…”

Section: Low-intensity Pulsed Ultrasound Treatmentmentioning

confidence: 86%

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Steroids are a leading cause of femoral head osteonecrosis. Currently there are no medications available to prevent and/or treat steroid-associated osteonecrosis. Low-intensity pulsed ultrasound (LIPUS) was approved by the FDA for treating delayed union of bone fractures. Some studies have reported that LIPUS can enhance bone formation and local blood flow in an animal model of fracture healing. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown.Questions/purposes We hypothesized that LIPUS may facilitate osteogenesis and neovascularization in the reparative processes of steroid-associated osteonecrosis. Using a rabbit animal model, we asked whether LIPUS affects (1) bone strength and trabecular architecture; (2) blood vessel number and diameter; and (3) BMP-2 and VEGF expression. Methods Bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in 24 rabbits. The left femoral heads of rabbits received LIPUS therapy (200 mW/cm 2 ) for 20 minutes daily and were classified as the LIPUS group. The right femoral heads of the same rabbits did not receive therapy and were classified as the control group. All rabbits were euthanized 12 weeks after LIPUS therapy. Micro-CT, biomechanical testing, histologic evaluation, immunohistochemistry, quantitative realtime PCR, and Western blot were used for examination of the effects of LIPUS. Results Twelve weeks after LIPUS treatment, the loading strength in the control group was 355 ± 38 N (95% CI, 315-394 N), which was lower (p = 0.028) than that in the LIPUS group (441 ± 78 N; 95% CI, 359-524 N). The bone tissue volume density (bone volume/total volume) in the LIPUS group (49.29% ± 12.37%; 95 % CI, 36.31%-62.27%) was higher (p = 0.022) than that in the control group (37.93% ± 8.37%; 95 % CI, 29.15%-46.72%). The percentage of empty osteocyte lacunae in the LIPUS group (17% ± 4%; 95% CI, 15%-20%) was lower (p = 0.002) than that in the control group (26% ± 9%; 95% CI, 21%-32%). The mineral apposition rate (lm/day) in the LIPUS group (2.3 ± 0.8 lm/day; 95% CI, 1.8 2.8 lm/day) was higher (p = 0.001) than that in the control group (1.6 ± 0.3 lm/day; 95% CL, 1.4-1.8 lm/day). The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm 2 ; 95% CI, 5.5-10.1 mm 2 ) was greater (p = 0.025) than the number in Hanxiao Zhu and Xunzi Cai contributed equally to this work and should be considered as co-first authors.The institution of the authors has received funding from the National Natural Science Foundation of China (Hangzhou, Zhejiang, China) (81101377, 81101345, 81171687, 81371954, 81201414, 81201416, 81401785, 81472113) 123Clin Orthop Relat Res (2015) 473:1830-1839 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® the control group (5.7 ± 2.6/mm 2 ; 95% CI, 4.0-7.3 mm 2 ). Messenger RNA (mRNA) and protein expression of BMP-2 in the LIPUS group (75 ± 7, 95% CI, 70-7...

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Section: Low-intensity Pulsed Ultrasound Treatmentmentioning

confidence: 86%

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…The metal to polyethylene interface is currently the most popular choice in joint replacement. Periprosthetic loosening caused by polyethylene debris is still the gold standard of joint loosening171819. This could help us best simulate microenvironmental changes in RAW 264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies have shown that ultrasound can reduce inflammatory swelling in rat hip infection model16. LIPUS also can induce osteogenesis and inhibit polyethylene particles induced in periprosthetic osteolysis in the current rabbit model17. However, the details of mechanism are still not clear.…”

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confidence: 88%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured. Results indicated that FBXL2-mediated TRAF6 ubiquitination and degradation also plays an important role in aseptic periprosthetic loosening process, and LIPUS prevents such loosening by strengthening this pathway.

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“…In a similar study, addition of lipopolysaccharide-coated polyethylene particles and addition of an antibody to sclerostin, an osteocyte-secreted molecule that interacts with LRP5/6 at the cell membrane, suppresses the Wnt signaling pathway [23]. Recent studies of osteolysis in the rabbit, a model that permits addition of particles into the medullary canal and analysis of cortical bone resorption, show that diverse treatment modalities inhibit bone turnover [30,34,61,62].…”

Section: Search Strategy and Criteriamentioning

confidence: 96%

“…The protease inhibitor bortezomib decreased osteolysis and importantly decreased formation of vascularized granulomatous tissue [25,26]. Addition of other agents, including berberine, captropril, dynastat, and N-acetyl-L-cysteine, decreased particle-dependent inflammation and associated osteolysis [14,16,60,61]. In studies taking advantage of knockout mutations, protein replacement of calcitonin and IL-6 increased bone and decreased inflammation, respectively, in calcitonin-negative and IL-6-negative animals [11,19].…”

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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Low-Intensity Pulsed Ultrasound (LIPUS) May Prevent Polyethylene Induced Periprosthetic Osteolysis In Vivo

Cited by 10 publications

References 37 publications

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

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

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