Arun S. Shanbhag

Clemson University, CEU, South Carolina, United States

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Publications (47)121.77 Total impact

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    ABSTRACT: Particulate wear debris from bone cement or prosthetic components can stimulate macrophages to cause bone resorption in a dose-dependent manner. This bone resorption activity of particulate-stimulated macrophages is associated with increased levels of both prostaglandin E2 (PGE2) and interleukin-1 (IL-1). In this study we compared the effect of particulate size, concentration, and composition on the secretion of IL-1 and PGE2 by peritoneal macrophages and on the bone-resorbing activity of conditioned medium (CM) harvested from particulate-challenged macrophages. Particulates (titanium, Ti; polymethylmethacrylate, PMMA; and polystyrene, PS) only with phagocytosable size stimulated peritoneal macrophages to secrete IL-1 and PGE2 in a dose- and time-dependent manner. Ti particles (1-3 microns) exhibited significantly enhanced bone-resorbing activity measured as 45Ca release. The maximum bone-resorbing response was observed at a concentration of 0.1% Ti (approximately 10-15 Ti particulates per cell), which also corresponded with the highest IL-1 levels measured in particulate-challenged CM. This was measured using either conditioned media from Ti-stimulated macrophages or in cocultures of calvarial bone and macrophages in the presence of Ti. Exogenous PGE2 and recombinant human IL-1 could significantly increase the 45Ca release; indomethacin (IM) significantly reduced both the spontaneous calcium efflux and active 45Ca release from in vivo labeled calvarial bones. However, IM and/or anti-IL-1 antibodies could suppress only partly the macrophage-mediated bone resorption, indicating that, in a macrophage-bone coculture system, factors other than PGE2 and IL-1 also may regulate particulate-induced bone resorption, probably involving multiple cell types.
    No preview · Article · Sep 2009 · Journal of Bone and Mineral Research
  • Adam M Kaufman · Claude I Alabre · Harry E Rubash · Arun S Shanbhag
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    ABSTRACT: Aseptic loosening of total joint replacements is believed to be initiated by a macrophage response to prosthetic wear debris. To better characterize the early response to clinically relevant wear debris, we challenged primary human macrophages from four donors with ultra high molecular weight polyethylene (UHMWPE), TiAlV, CoCr, and alumina particles. After a 24-h culture, protein arrays were used to quantify the secretion of 30 different cytokines and chemokines. Macrophages secreted detectable levels of nine mediators in culture: Interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, MCP-1, IL-8, IL-6, GM-CSF, IL-10, and IL-12p40. TiAlV particles were the most stimulatory, causing 5- to 900-fold higher cytokine expression compared with nonstimulated cells and uniquely eliciting high levels of IL-1alpha, IL-6, IL-10, and GM-CSF. CoCr and alumina were mildly stimulatory and typically elicited two- to fivefold greater levels than nonstimulated cells. Surprisingly, UHMWPE did not elicit a significant increase in cytokine release. Our data suggests that IL-1alpha, TNF-alpha, IL-1beta, and MCP-1 are the primary initiators of osteolysis and implicates metallic debris as an important trigger for their release.
    No preview · Article · Feb 2008 · Journal of Biomedical Materials Research Part A
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    ABSTRACT: The long-term durability of total joint replacements is critically dependent on adequate peri-implant bone stock, which can be compromised by wear debris-mediated osteolysis. This study investigated the effects of bisphosphonates on enhancing peri-implant bone in the presence of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium-alloy plugs were implanted bilaterally in the femoral condyles of 36 New Zealand white rabbits. Implants in the left femora were covered with submicron UHMWPE particles during surgery. Rabbits were administered either no drug, subcutaneous alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate (0.015mg/kg). A total of 6/12 rabbits in each group were sacrificed at 6 weeks and the remainder at 12 weeks postoperatively. Peri-implant bone stock was analyzed radiographically and histomorphometrically. Radiographically, both bisphosphonates significantly increased periprosthetic cortical thickness at 6 weeks (p<0.0001; alendronate: +18%; zoledronate: +11%) and at 12 weeks (p=0.001; alendronate: +17%; zoledronate:+19%). Histomorphometrically, alendronate and zoledronate raised peri-implant bone volume (BV/TV) up to 2-fold after 6 weeks without added wear debris and more than 3-fold when wear debris was present. Furthermore a 6-week bisphosphonate treatment increased osteoid thickness in the absence of wear debris (alendronate: +132%, p=0.007; zoledronate: +67%, p=0.51) and in the presence of wear debris (alendronate: +134%, p=0.023; zoledronate: +138%, p=0.016). In summary, alendronate and zoledronate treatment increased periprosthetic bone stock in a rabbit femoral model, particularly in the presence of UHMWPE wear debris. These new findings suggest that bisphosphonates may more than compensate for the well-documented negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty.
    No preview · Article · Aug 2007 · Biomaterials
  • Arun S Shanbhag · Adam M Kaufman · Koichiro Hayata · Harry E Rubash
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    ABSTRACT: Previous studies of bone resorption around failed joint replacements have focused on a limited number of cytokines, primarily tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, with use of enzyme-linked immunosorbent assay and immunohistochemistry techniques. In this study, we utilized high-throughput protein chips to profile twenty-nine inflammatory cytokines around failed total joint replacements. Peri-implant granulomatous tissues were harvested from around the failed total hip prostheses of thirteen patients. Synovial lining capsular tissues from thirteen patients with end-stage degenerative joint disease were used as controls. After homogenization, twenty-nine cytokines were quantified with use of high-throughput protein chips. IL-6 and IL-8 were found consistently in failed joint replacement tissues, reaffirming their prominent role in osteoclastogenesis and end-stage bone resorption. High levels of interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (MIG), both chemoattractants of activated Th1 lymphocytes, were also detected. Soluble intercellular adhesion molecule (sICAM) and transforming growth factor-beta1 (TGF-beta(1)) were not detected universally, nor were TNF-alpha or IL-1. After a twenty-four-hour organ culture, IL-1beta levels increased substantially along with those of other mediators. We measured but did not detect any activators of cytotoxic T-cells, antibody-producing Bcells, or eosinophils involved in delayed-type hypersensitivity. Variations from patient to patient were seen across all cytokines and highlight the unique response of individual patients to their joint replacements. In failed total joint replacements in patients with end-stage osteolysis, IL-6 and IL-8 may be the primary drivers of osteoclastogenesis. The presence of IP-10 and MIG imply a role for T-cells, while TGF-beta(1) and sICAM may represent a systemic attempt to modulate the inflammation. TNF-alpha and IL-1 do not appear to play a major role in the end stages of the disease.
    No preview · Article · Jun 2007 · The Journal of Bone and Joint Surgery
  • Carl T Talmo · Arun S Shanbhag · Harry E Rubash
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    ABSTRACT: Osteolysis remains a common mode of total hip arthroplasty failure. In vitro and animal models have been used to determine the pathophysiology of osteolysis by carefully dissecting the biochemical pathways leading to particulate wear debris and periprosthetic bone loss. Numerous cytokines and inflammatory mediators, including TNF-alpha and IL-1, are critical participants in this cascade and may represent prime targets for pharmacologic intervention. Osteoclasts, the end effector cells involved in the osteolytic process, also represent potential targets. Cell surface receptors on osteoclast precursors, such as receptor activator of NF-kappaB (RANK) (on osteoclasts) and RANK-ligand (RANKL) (on stromal cells), provide opportunities to arrest osteoclast maturation. Enhancing the naturally occurring osteoprotegerin is another recent attempt at modulating osteoclast behavior and a possible target for pharmacologic therapies. Other nonoperative strategies include intercepting tumor necrosis factor-alpha activity, interfering with the RANK-RANKL interaction necessary for osteoclast development and maturation, bisphosphonate therapy, and using viral vectors to deliver genes. Although each of these approaches has potential benefits, there are substantial challenges to effective implementation. Until there is convincing evidence of efficacy in human clinical trials, we recommend vigilant screening and appropriate surgery with component loosening or substantial likelihood of loosening, periprosthetic fracture, or major bone loss.
    No preview · Article · Jan 2007 · Clinical Orthopaedics and Related Research
  • Arun S Shanbhag
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    ABSTRACT: Total joint arthroplasty is very effective for improving the quality of life of patients with end-stage arthritis. Despite advances in materials, surgical technique, and rehabilitation regimens, joint replacements are still fraught with complications leading to their premature failure. Aseptic loosening and osteolysis are the primary causes of implant failure. Other reasons include early migration of components leading to instability, lack of ingrowth into implant porosities, and bone loss caused by stress shielding. Pharmaceutical agents used for preventing and managing postmenopausal osteoporosis (eg, bisphosphonates) may in the future play an important role in improving the long-term duration of joint arthroplasties. Early findings indicate that bisphosphonates upregulate bone morphogenetic protein-2 production and stimulate new bone formation. Because of their anabolic effect on osteoblasts, bisphosphonates have the potential to enhance bone ingrowth into implant porosities, prevent bone resorption under adverse conditions, and dramatically extend the long-term durability of joint arthroplasties. The long-term effects of bisphosphonate use on the mechanical properties of bone have not been adequately investigated. Along with improvements in implant design and material properties, bisphosphonates and other pharmaceutical agents may, in the near future, be part of the growing armamentarium that provides more durable joint arthroplasties.
    No preview · Article · May 2006 · The Journal of the American Academy of Orthopaedic Surgeons
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    ABSTRACT: A total of 750 images of individual ultra-high molecular weight polyethylene (UHMWPE) particles isolated from periprosthetic failed hip, knee, and shoulder arthroplasties were extracted from archival scanning electron micrographs. Particle size and morphology was subsequently analyzed using computerized image analysis software utilizing five descriptors found in ASTM F1877-98, a standard for quantitative description of wear debris. An online survey application was developed to display particle images, and allowed ten respondents to classify particle morphologies according to commonly used terminology as fibers, flakes, or granules. Particles were categorized based on a simple majority of responses. All descriptors were evaluated using a one-way ANOVA and Tukey-Kramer test for all-pairs comparison among each class of particles. A logistic regression model using half of the particles included in the survey was then used to develop a mathematical scheme to predict whether a given particle should be classified as a fiber, flake, or granule based on its quantitative measurements. The validity of the model was then assessed using the other half of the survey particles and compared with human responses. Comparison of the quantitative measurements of isolated particles showed that the morphologies of each particle type classified by respondents were statistically different from one another (p<0.05). The average agreement between mathematical prediction and human respondents was 83.5% (standard error 0.16%). These data suggest that computerized descriptors can be feasibly correlated with subjective terminology, thus providing a basis for a common vocabulary for particle description which can be translated into quantitative dimensions.
    No preview · Article · Feb 2006 · Biomaterials
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    ABSTRACT: Bisphosphonates are well known potent inhibitors of osteoclast activity and are widely used to treat metabolic bone diseases. Recent evidence from in vitro and in vivo studies indicates that bisphosphonates may additionally promote osteoblastic bone formation. In this study, we evaluated the effects of three FDA-approved and clinically utilized bisphosphonates, on the proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC). BMSC were obtained from patients undergoing primary total hip arthroplasty for end-stage degenerative joint disease. Cells were treated with or without a bisphosphonate (alendronate, risedronate, or zoledronate) and analyzed over 21 days of culture. Cell proliferation was determined by direct cell counting. Osteogenic differentiation of BMSC was assessed with alkaline phosphatase bioassay and gene expression analyses using conventional RT-PCR as well as real-time quantitative RT-PCR. All bisphosphonates tested enhanced the proliferation of BMSC after 7 and 14 days of culture. Steady-state mRNA levels of key genes involved in osteogenic differentiation such as bone morphogenetic protein-2 (BMP-2), bone sialoprotein-II, core-binding factor alpha subunit 1 (cbfa1) and type 1 collagen, were generally increased by bisphosphonate treatment in a type- and time-dependent manner. Gene expression levels varied among the different donors. Enhancement of osteogenic differentiation was most pronounced after 14 days of culture, particularly following zoledronate treatment (p < 0.05 for BMP-2). In conclusion, using a clinically relevant in vitro model we have demonstrated that bisphosphonates enhance proliferation of BMSC and initiate osteoblastic differentiation. When administered around joint replacements, bisphosphonates may potentially compensate for the deleterious effects of particulate wear debris at the bone-implant interface, by encouraging increased numbers of cells committed to the osteoblastic phenotype, and thus improve the longevity of joint replacements.
    Full-text · Article · Jan 2006 · Biomaterials
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    ABSTRACT: Alendronate and other bisphosphonates are clinically efficacious in treating postmenopausal osteoporosis, Paget's disease and hypercalcemia associated with malignancy. Because bisphosphonates are being considered for use in younger patients with joint replacements to prevent osteolysis, and for stress fracture prophylaxis in military recruits, it is important to know how bisphosphonate therapy affects healthy bone. We sought to determine whether bones from healthy male dogs exhibit alterations in structural or mechanical properties following alendronate treatment for 23 weeks. We tested trabecular tissue samples in compression and determined tissue ash density. We tested whole long bones in bending and torsion. For trabecular samples, we evaluated trabecular modulus, strength, and density. For whole bone specimens, we compared structural stiffness and ultimate load. We found no significant differences in any measure, between canines treated with alendronate for 23 weeks and controls, although we found consistent trends toward higher properties in the treated group. Correlation analysis revealed significant relationships between stiffness and strength measures for each mechanical test. Our results indicate bisphosphonate treatment in healthy canines does not weaken the properties of bone. The trends indicate a slight positive overall effect of alendronate treatment on the mechanical properties of healthy canine bone.
    No preview · Article · Jan 2006 · Journal of Biomedical Materials Research Part B Applied Biomaterials
  • Arun Shanbhag

    No preview · Article · Aug 2005 · Biomaterials
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    ABSTRACT: The most common cause of total joint replacement failure is peri-implant bone loss causing pain and prosthesis loosening. This process, known as osteolysis or aseptic loosening, is characterized by macrophage phagocytosis of particulate implant wear debris. In an incompletely defined step, particulate biomaterial debris induces macrophages to release a variety of inflammatory mediators and signaling proteins that lead to bone loss. In an in vitro model of this process, we used microarray technology and data analysis techniques, including the use of self-organizing maps (SOMs), to understand the mRNA gene expression changes occurring in macrophages exposed to clinically relevant particles of ultra-high molecular weight polyethylene and TiAlV alloy. Earlier studies have been limited by technology that only allowed analysis of a few genes at a time, but the microarray techniques used in this paper generate the quantitative analysis of over a thousand genes simultaneously. Our microarray analysis utilized an SOM clustering to elucidate general patterns in the data, lists of top up- and down-regulated genes for each time point and genes with differential expression under different biomaterial exposures. The expression levels of the majority of genes (>95%) did not vary over time or with exposure to different biomaterials, but a few important genes, such as TNF-alpha, IL-1beta, IL-6, and MIP1alpha, proved to be highly regulated in response to biomaterial exposure. We also uncovered a novel set of genes, which not only validates and logically extends the current model of the pathogenesis of osteolysis and aseptic loosening, but also provides new targets for further research and therapeutics.
    No preview · Article · Jul 2005 · Biomaterials
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    ABSTRACT: Aseptic loosening and osteolysis are currently the most common causes of failure of total joint replacements. Osteolysis is initiated by a macrophage response to wear debris, resulting in localized, osteoclastic peri-implant bone loss. We have previously inhibited osteoclast-mediated bone resorption in a canine total hip arthroplasty model using oral bisphosphonate therapy. Based on serendipitous observations from our canine study, we hypothesized that bisphosphonates have an anabolic effect on osteoblasts, in a manner distinct from their inhibitory effect on osteoclastic bone resorption. We studied the anabolic effects of two FDA-approved bisphosphonates (alendronate and risedronate) on two in vitro models: a primary human trabecular bone cell culture and the MG-63 osteoblast-like cell line. Following treatment with bisphosphonates at varying concentrations and time periods, cells were assayed for proliferation effects and results were quantified using the methods of direct cell count, and the colorimetric MTT (3-dimethylthiazol-2,5-diphenyltetrazolium bromide) assay at 24, 48, and 72 h. The effect of bisphosphonates on the maturation of osteoblasts were tested with alkaline phosphatase bioassay and reverse transcription-polymerase chain reaction for markers of osteoblast differentiation. Results from both the primary human trabecular bone cell culture and the MG-63 osteoblast-like cell line showed that both bisphosphonates significantly increased the cell number over controls, attaining peak levels at a concentration of 10(-8)M. Alkaline phosphatase activity was also increased, representing earlier commitment of osteoprogenitor cells towards the osteoblastic phenotype. Bisphosphonates also enhanced gene expression of BMP-2, Type I collagen and osteocalcin. In summary, bisphosphonates, aside from their role as inhibitors of osteoclastic bone resorption, are promoters of osteoblast proliferation and maturation.
    No preview · Article · Sep 2004 · Biomaterials
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    Rajiv K Sethi · Mark J Neavyn · Harry E Rubash · Arun S Shanbhag
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    ABSTRACT: To prevent wear debris-induced osteolysis and aseptic loosening, cross-linked ultra-high molecular weight polyethylene's (UHMWPE) with improved wear resistance have been developed. Hip simulator studies have demonstrated very low wear rates with these new materials leading to their widespread clinical use. However, the biocompatibility of this material is not known. We studied the macrophage response to cross-linked UHMWPE (XLPE) and compared it to conventional UHMWPE (CPE) as well as other clinically used orthopaedic materials such as titanium-alloy (TiAlV) and cobalt-chrome alloy (CoCr). Human peripheral blood monocytes and murine macrophages, as surrogates for cells mediating peri-implant inflammation, were cultured onto custom designed lipped disks fabricated from the test materials to isolate cells. Culture supernatants were collected at 24 and 48h and analyzed for cytokines such as IL-1alpha, IL-1beta, TNF-alpha and IL-6. Total RNA was extracted from adherent cells and gene expression was analyzed using qualitative RT-PCR. In both in vitro models, macrophages cultured on cross-linked and conventional polyethylene released similar levels of cytokines, which were also similar to levels on control tissue culture dishes. Macrophages cultured on TiAlV and CoCr-alloy released significantly higher levels of cytokines. Human monocytes from all donors varied in the magnitude of cytokines released when cultured on identical surfaces. The variability in individual donor responses to TiAlV and CoCr surfaces may reflect how individuals respond differently to similar stimuli and perhaps reveal a predisposed sensitivity to particular materials.
    Full-text · Article · Aug 2003 · Biomaterials
  • G.-I. Im · A.S. Shanbhag · R. Berger · H.E. Rubash
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    ABSTRACT: Osteolysis is the consequence of biological activity in response to particulate debris at the bone-implant interface. Despite the documented problem of knee component wear, osteolysis around total knee arthroplasty (TKA) has only recently been recognized as a clinical problem. There are important differences between wear particles from TKA and total hip arthroplasty (THA) that are attributed to kinematic differences between the two joints. These factors and others determine the variation in biological response and the subsequent incidence of osteolysis in joint replacements. In this review, we compared the pathophysiology of osteolysis in TKA and THA, including wear debris production and the biological response to particulate debris. We also summarized the incidence of osteolysis in TKA based on previously published reports. Finally, the principles of the diagnosis and management of osteolysis after TKA are reviewed.
    No preview · Article · Oct 2002 · Seminars in Arthroplasty
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    ABSTRACT: Numerous in vitro models have demonstrated the capacity of wear particles to stimulate the release of soluble pro-inflammatory products with the ability to induce local bone resorption. Recent observations have demonstrated that binding of lipopolysaccharide (LPS) to particulate wear debris can significantly modulate the pattern of cell response in the in vitro models. These findings raise concerns over the possible role of LPS in the pathogenesis of aseptic loosening after total joint replacements, and also indicates the importance of controlling for possible confounding effects of LPS contamination in the in vitro models used to study the reactive nature of wear debris. Our studies were undertaken to rigorously analyze the effects of particle-associated LPS on cell responses and to assess the efficacy of different treatment protocols to inactivate LPS associated with different particulate materials. Particles of cobalt-chrome alloy, titanium-6-aluminum-4-vanadium, titanium nitride and silica were pretreated with LPS and exposed to multiple treatment protocols. When cells were treated with "as-received" particles prepared by washing in ethanol, small amounts of TNF-alpha, IL-1beta. and IL-1alpha were detected. In contrast, all particle species pretreated with LPS produced marked increases in TNF-alpha, IL-1alpha, and IL-1beta release, as well as upregulation of corresponding mRNA levels even after ethanol washing. Boiling the LPS-pretreated particles in 1% acetic acid or autoclaving and baking the particles also markedly reduced and in some instances abolished the effect of the LPS-pretreatment. This indicates that LPS binds to the surface of particles of diverse composition and that the bound LPS is biologically active. Treatment protocols to inactivate particle-associated LPS demonstrated significant differences in efficacy. When the most rigorous treatments were utilized, essentially all LPS activity could be eliminated. Particles treated with these methods retained some capacity to stimulate cytokine release, but activities were markedly reduced. These results provide further evidence indicating that LPS contamination of particulate materials can markedly enhance their biological activity. This potential confounding effect needs to be carefully monitored and controlled in the in vitro model systems used to evaluate wear particles. Furthermore, the presence of particle-associated endotoxin at the bone-implant interface in vivo could markedly enhance the adverse biological activity of particulate wear debris.
    Full-text · Article · Aug 2002 · Journal of Orthopaedic Research
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    ABSTRACT: The size and morphology of particulate wear debris retrieved from tissues around 18 failed total knee replacements (TKR) were characterized. Interfacial membranes from nine cemented and nine uncemented TKR were harvested from below the tibial components during revision surgery. Wear debris were extracted using papain and potassium hydroxide digestion. Ultrahigh molecular weight polyethylene (UHMWPE) particles from around cemented or uncemented TKR were similar in size and morphology. The mean size was 1.7 +/- 0. 7 microm with a range of 0.1-18 microm. Thirty-six percent of the particles were less than 1 microm and 90% were less than 3 microm. Morphologically the particles were predominantly spherical with occasional fibrillar attachments and flakes. Particles from TKR were greater than threefold larger than previously characterized particles from total hip replacements, which were 0.5 microm in mean size. Differences in joint conformity and wear patterns between the hip and knee articulations may explain the disparity in size of the wear debris. Since particle size represents an important variable influencing the magnitude of the biological response, it is possible that in vivo the larger TKR debris results in a diminished mediator release, which in turn may account for the lower incidence of osteolysis and aseptic loosening in some designs of TKR.
    No preview · Article · Feb 2000 · Journal of Biomedical Materials Research
  • Xiaodu Wang · Arun S. Shanbhag · Harry E. Rubash · C. Mauli Agrawal
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    ABSTRACT: Periprosthetic osteolysis and aseptic loosening of total joint replacements are believed to be initiated often by abnormal bone resorption induced by prosthetic wear debris. Bisphosphonates can inhibit bone resorption and have been successfully used clinically to treat osteoporosis and Paget's disease. In a recent study it also was shown that a third generation bisphosphonate (alendronate) is effective in preventing wear debris-induced periprosthetic osteolysis. Since inhibition of bone resorption by alendronate may disrupt the delicate balance between bone resorption and formation in normal bone remodeling, it is possible that continuous alendronate therapy may have an adverse effect on the biomechanical properties of bone. Thus the purpose of the present study was to examine the effects of systemic alendronate administration on the biomechanical properties of normal bone using a canine total hip arthroplasty model. We evaluated the biomechanical properties of femora from canines that had received total hip replacements on one side and had been given oral alendronate daily for 23 weeks. The biomechanical properties assessed were fracture toughness, elastic modulus, tensile strength, microhardness, porosity, and weight fractions of the mineral and organic phases of bone. Also, bone microstructure was examined using optical microscopy. Our results indicate that in the short term alendronate therapy does not have any adverse effects on the intrinsic biomechanical properties of canine bone. However, the long-term effects of alendronate therapy still need to be investigated.
    No preview · Article · Apr 1999 · Journal of Biomedical Materials Research
  • Ick‐Hwan Yang · Shin‐Yoon Kim · Harry E. Rubash · Arun S. Shanbhag
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    ABSTRACT: Biologic response to generated wear particles and subsequent aseptic loosening is a critical factor limiting the long-term survival of total hip replacements. To better understand the sequence of events leading to aseptic loosening and the role of the individual material components, fabricating metal particles similar to those present clinically is very important. We describe a simple milling technique to generate significant amounts of fine titanium-alloy (TiAlV) debris. A TiAlV rod was milled against a TiAlV plate in distilled water supplemented with antibiotics. The resulting debris were sedimented in alcohol and the fine debris were separated. Scanning electron microscopy analysis and particle size analysis demonstrated that the mean size of particles was 1.1 +/- 0.9 microm (range 0.2-4.2 microm). Sixty-two percent were smaller than 1.0 microm, and 85% were smaller than 2.0 microm. The particles generated had varying shapes, including angular or shard-like shapes with jagged and irregular outlines.
    No preview · Article · Feb 1999 · Journal of Biomedical Materials Research
  • Arun S. Shanbhag · Harry E. Rubash
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    ABSTRACT: Aseptic loosening is the number one impediment to extending the useful life span of total joint replacements. The etiologic agent is believed to be submicron ultrahigh molecular weight polyethylene debris from the acetabular liner, which stimulates a macrophage-mediated inflammatory response. Therapeutic approaches using bisphosphonates represent a convenient and effective manner to target the end effector cell, which is the osteoclast. The studies reviewed here highlight the encouraging prospects of using bisphosphonates to prevent and potentially treat periprosthetic bone loss associated with osteolysis. There appear to be minimal complications, and the mechanisms of action are fairly well understood. Thus, bisphosphonates are appropriate candidates in a growing repertoire of materials development, implant design, and pharmaceutical agents to combat periprosthetic osteolysis.
    No preview · Article · Dec 1998 · Current Opinion in Orthopaedics
  • SY Kim · RK Sinha · AS Shanbhag · HE Rubash

    No preview · Article · Oct 1998 · Orthopedic Clinics of North America

Publication Stats

3k Citations
121.77 Total Impact Points


  • 1992-2009
    • Clemson University
      • Department of Bioengineering
      CEU, South Carolina, United States
  • 1998-2008
    • Harvard Medical School
      • Department of Orthopaedic Surgery
      Boston, Massachusetts, United States
  • 2007
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2006
    • University of Texas at San Antonio
      • College of Engineering
      San Antonio, Texas, United States
  • 2005-2006
    • Massachusetts General Hospital
      • Department of Orthopaedic Surgery
      Boston, MA, United States
  • 1996-2006
    • University of Pittsburgh
      • Department of Orthopaedic Surgery
      Pittsburgh, Pennsylvania, United States
  • 1995
    • Rush Medical College
      Chicago, Illinois, United States
    • Rush University Medical Center
      • Department of Biochemistry
      Chicago, Illinois, United States
    • Aurora St. Luke's Medical Center
      Milwaukee, Wisconsin, United States