Search

Several acetabular components utilizing novel ultraporous metal substrates have been introduced over the past decade. Collectively by design, they have a lower modulus of elasticity to reduce stress shielding, a higher coefficient of friction to enhance interference fit, and ultraporous surfaces to enhance osseointegration. However, little literature exists regarding their clinical performance.This study compared the clinical and radiographic results of 109 hips in 95 patients using a Tritanium primary cup (Stryker, Mahwah, NJ) to an age, body mass index, and gender-matched cohort of 100 patients that received a contemporary cup (Stryker Trident PSL HA).At an average 4.24 + 1.49 years, implant survivorship of the Tritanium primary cup was 98.2%, with 2 cups revised for failure of osseointegration. One-year radiographs revealed radiolucent and radiosclerotic lines in 2 or more DeLee zones in 30.3% of cups and 3 zone involvement in 8.2%. These proportions increased (40.0% and 17.1%, respectively) at minimum 5-year follow-up. A comparison of 1 year and last follow-up radiographs revealed progression in 13.8%. Tritanium primary components with radiolucency in 2 or more zones exhibited significantly lower HHS at 2 years compared to all Trident peripheral self-locking (PSL) components (P.0001) and Tritanium primary components with 1 zone or no radiolucency (P = .026). Scanning electron microscopy of a retrieved cup revealed local inflammatory reaction and no evidence of osseointegration.Despite adequate implant survivorship, over one third of Tritanium primary cups had 2 or more zone radiolucency at minimum 5-year follow-up with associated lower Harris hip scores.

Press-fit, hydroxyapatite-coated acetabular cup designs may offer a lower incidence of loosening and migration than older designs. Our study evaluated the initial clinical and radiographic success of a cementless acetabular shell in a large cohort of primary total hip arthroplasty (THA) patients. We queried our institution’s prospectively collected registry for a series of 771 primary THAs (695 patients) implanted with this cup by 4 high-volume arthroplasty surgeons. Of the 613 hips with minimum 2-year followup, average HHS (Harris Hip Score) was 93.6, WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was 87.6, and VAS (Visual Analog Scale) pain score was 1.2. While there was a 2% reoperation rate (12 hips), none of the cups were revised for aseptic loosening. No radiolucencies were found and there was no evidence of acetabular loosening. At early followup, this newer cementless acetabular cup implant design exhibits high survivorship and clinical success.

Activation of myeloid cells by orthopedic particulate debris is a key event in the pathogenesis of periprosthetic osteolysis and implant loosening after total joint replacement (TJR). Several lines of evidence implicate NACHT, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome-mediated production of interleukin 1 beta (IL-1β) in the pathogenesis of clinical disorders ascribable to foreign particulate materials, including asbestos, silica, and urate crystals. Recent reports indicate that orthopedic polymer products and metallic particulates and ions may activate the same pathway. Here, we investigated the contribution of the NALP3 inflammasome to the pathogenesis of peri-implant osteolysis. Pharmaceutical and genetic perturbations of caspase-1 and inflammasome components were used to assess the role of the NALP3 inflammasome in IL-1β production and osteoclast formation by human monocytes and mouse macrophages in response to polymethylmethacrylate (PMMA) particle phagocytosis. The role of caspase-1 in a mouse calvarial model of particle-mediated osteolysis was assessed using µCT. Phagocytosis of PMMA particles induces caspase-1 dependent release of IL-1β from human monocytes and mouse macrophages. Importantly, using macrophages from mice deficient in components of the NALP3 inflammasome, we show PMMA-induced IL-1β production is strictly dependent on these components. Mice lacking caspase-1, the sole effector of the NALP3 inflammasome, show reduced orthopedic wear particle-induced calvarial osteolysis compared to wild-type controls. Absence of NALP3 inflammasome components fails to alter osteoclast formation in vitro. Our findings identify the NALP3 inflammasome as a critical mediator of orthopedic wear-induced osteolysis and as a viable therapeutic target for the treatment of periprosthetic osteolysis.

Alternative bearing materials in THA have been developed to reduce the incidence of osteolysis. Alumina-on-alumina bearings exhibit extremely low wear rates in vitro, but concerns exist regarding component impingement with the potential for dislocation and the occurrence of noise.We determined generation of squeaking and the relationship between squeaking and component position.We prospectively entered 436 alumina-on-alumina, cementless, primary THAs in 364 patients into our institutional database. All procedures were performed with the same surgical technique and the same implant. We obtained Harris Hip scores and a noise questionnaire and assessed radiographic component position and loosening. We determined the difference in abduction angle between squeakers and nonsqueakers. Minimum followup was 2 years (average, 3.5 years; range, 2.0-6.2 years).The mean Harris hip score increased from 51.9 preoperatively to 94.4 at latest followup. Six hips underwent reoperation: four hips (1.1%) for dislocation and two (0.53%) for periprosthetic fracture after trauma. The incidence of noise of any type was 11%, with the most common type of noise being clicking or snapping. Squeaking was reported by 1.9% of patients, with no patient being revised for this phenomenon. We found no association between component position and squeaking.At average 3 years followup, 98% of ceramic-on-ceramic THAs did not require a revision, with 1.1% of hips having been revised for dislocation. Fewer than 2% of patients reported hearing an audible squeak, with no association found between component position and squeaking.Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

During granulomatous inflammatory reactions, myeloid cells can differentiate into activated phagocytic macrophages, wound-healing macrophages, foreign body giant cells, and bone-resorbing osteoclasts. Although it is appreciated that a variety of stimuli, including cytokines, cell–matrix interactions, and challenge with foreign materials can influence myeloid cell fate, little is known of how these signals integrate during this process. In this study, we have investigated the cross talk between receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and particle phagocytosis-induced activation of human monocytes. Understanding interconnected signals is of particular importance to disorders, such as periprosthetic osteolysis, in which granulomatous inflammation is initiated by particle phagocytosis in proximity to bone and leads to inflammatory bone loss. Using cell-based osteoclastogenesis and phagocytosis assays together with expression analysis of key regulators of osteoclastogenesis, we show in this study that phagocytosis of disease-relevant particles inhibits RANKL-mediated osteoclastogenesis of human monocytes. Mechanistically, phagocytosis mediates this effect by downregulation of RANK and c-Fms, the receptors for the essential osteoclastogenic cytokines RANKL and M-CSF. RANKL pretreatment of monocytes generates preosteoclasts that are resistant to RANK downregulation and committed to osteoclast formation, even though they retain phagocytic activity. Thus, the relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate.

Between December 1996 and April 2003, 26 consecutive femoral component revisions in 24 patients were performed with an extensively hydroxyapatite-coated femoral stem. Two patients were lost to follow-up, and two patients died of unrelated causes. Of the 22 femoral revisions in 20 patients, there was a 0% incidence of mechanical loosening at average follow-up of 3.2 years (2–6.3 years). The Harris Hip Score improved from 59 (36 to 83) to 95 (84 to 100) postoperatively ( p < 0.001). Rate of revision was 18.2% (4.5% for sepsis, 9.1% for instability, and 4.5% for polyethelene wear). All 22 femoral components had evidence of bone ingrowth. The extensively coated hydroxyapatite stem in this series produced excellent clinical results with a low incidence of thigh pain (4.5%) and severe stress shielding (4.5%).

Interactions between periprosthetic cells and prosthetic wear debris have been recognized as an important event in the development of osteolysis and aseptic loosening. Although the ability of wear debris to activate pro-inflammatory macrophage signaling has been documented, the full repertoire of macrophage responses to wear particles has not been established. Here, we examined the involvement of alternative macrophage activation and defective osteogenic signaling in osteolysis. Using real-time RT-PCR analysis of periprosthetic soft tissue from osteolysis patients, we detected elevated levels of expression of alternative macrophage activation markers (CHIT1, CCL18), chemokines (IL8, MIP1 alpha) and markers of osteoclast precursor cell differentiation and multinucleation (Cathepsin K, TRAP, DC-STAMP) relative to osteoarthritis controls. The presence of cathepsin K positive multinuclear cells was confirmed by immunohistochemistry. Reduced expression levels of the osteogenic signaling components BMP4 and FGF18 were detected. Expression levels of TNF-alpha, IL-6, and RANKL were unchanged, while the anti-osteoclastogenic cytokine OPG was reduced in osteolysis patients, resulting in elevated RANKL:OPG ratios. In vitro studies confirmed the role of particulate debris in alternative macrophage activation and inhibition of osteogenic signaling. Taken together, these results suggest involvement in osteolysis of alternative macrophage activation, accompanied by elevated levels of various chemokines. Increased recruitment and maturation of osteoclast precursors is also observed, as is reduced osteogenesis. These findings provide new insights into the molecular pathogenesis of osteolysis, and identify new potential candidate markers for disease progression and therapeutic targeting.

Five patients presented with fiber metal mesh shedding of a Harris Galante II acetabular cup detected between 11 and 15 years after implantation. All patients presented with hip pain and 4 demonstrated gross acetabular loosening and fiber metal separation on preoperative radiographs. The remaining patient underwent revision surgery because of a liner dislodgment and had a radiographically well fixed shell. Loosening and fiber metal separation were detected intraoperatively. Scanning electron microscopy of the retrieved shells demonstrated isolated diffusion bonding marks in the areas where the mesh separated from the substrate and no evidence of corrosion. Progressive osteolysis in the iliac bone was evident in 4 of our cases. Progressive iliac osteolysis may lead to loss of bone support in well-fixed cups and excessive stresses transferred to the interface between the fiber metal mesh and the titanium substrate leading to the separation of the 2 layers. Fiber metal separation may contribute to long-term loosening in the Harris Galante acetabular component.

The generation of prosthetic implant wear after total joint arthroplasty is recognized as the major initiating event in development of periprosthetic osteolysis and aseptic loosening, the leading complication of this otherwise successful surgical procedure. We review current concepts of how wear debris causes osteolysis, and report ideas for prevention and treatment. Wear debris primarily targets macrophages and osteoclast precursor cells, although osteoblasts, fibroblasts, and lymphocytes also may be involved. Molecular responses include activation of MAP kinase pathways, transcription factors (including NFkappaB), and suppressors of cytokine signaling. This results in up-regulation of proinflammatory signaling and inhibition of the protective actions of antiosteoclastogenic cytokines such as interferon gamma. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties should be balanced by awareness that reducing particle size may increase biologic activity. There are no approved treatments for osteolysis despite the promise of therapeutic agents against proinflammatory mediators (such as tumor necrosis factor) and osteoclasts (bisphosphonates and molecules blocking receptor activator of NFkappaB ligand [RANKL] signaling) shown in animal models. Considerable efforts are underway to develop such therapies, to identify novel targets for therapeutic intervention, and to develop effective outcome measures.

Dislocation following hip arthroplasty remains problematic. While the etiology of dislocation may be multifactorial, implant system design may play a role. Using a computer aided design program, virtual range of motion of several commonly implanted designs was performed with prosthetic interference representing impingement used as an endpoint. Implants with small diameter head size (22mm) and a larger trunion geometry (type II taper) demonstrated impingement in flexion at less than 90°, suggesting an increased risk for dislocation. To investigate this clinically, we performed a review of a consecutive series of 254 primary hip arthroplasties performed by a single surgeon using an implant with a type II taper (Biomet™, Warsaw, IN). At a minimum 2 year followup, 12 patients with 12 hips (4.8%) had at least one episode of dislocation. Stratified by head size, the dislocation rates were 3.6% for 28 mm, 4.8% for 26 mm, and 18.8% for 22mm bearings. These findings support the notion that computer aided design modeling of implant systems is useful in evaluating range of motion and this technique could be employed during the design of any new implant system. Level of Evidence: Therapeutic study, level IV (case series). See Guidelines for Authors for a complete description of levels of evidence.

Background Wear debris challenge of macrophages provokes the generation of proinflammatory cytokines, which contribute to periprosthetic osteolysis. However, it is not known whether this effect is accompanied by reprogramming of other cytokines present within the periprosthetic tissue that may be involved in anti-osteoclastogenic activities. In the present study, we examined the ability of wear debris particles to inhibit the signaling of two such cytokines, interleukin-6 and interferon-γ. Methods Human osteoclast precursor cells were challenged with particles of titanium or polymethylmethacrylate bone cement prior to the addition of the cytokines interleukin-6 or interferon-γ(?Interleukin-6 signaling was determined by measuring the activation of STAT3 signal transduction with use of immunoblotting and electrophoretic mobility shift assays. Interferon-γ signaling was determined by measuring the activation of STAT1 with use of immunoblotting and electrophoretic mobility shift assays and by measuring the expression of interferon-γ-inducible genes with use of real-time reverse transcription-polymerase chain reaction assays. Involvement of mitogen-activated protein kinases in cytokine signaling was assessed by including mitogen-activated protein kinase inhibitors in these assays and also by means of immunoblot assessment of mitogen-activated protein kinase activation by wear debris particles. Wear debris modulation of expression of the cytokine suppressors SOCS1 and SOCS3 (as well as pro-inflammatory mediators) was assessed with use of real-time reverse transcription-polymerase chain reaction assays. Results Both titanium and polymethylmethacrylate particles potently inhibited interleukin-6-induced STAT3 activation in human osteoclast precursor cells. Inhibition of p38 mitogen-activated protein kinase, which is activated by titanium and polymethylmethacrylate, reversed the inhibitory effects of these particles on interleukin-6 signaling, whereas inhibition of ERK and JNK mitogen-activated protein kinases (which are also activated by both types of wear debris) had no effect. Titanium and polymethylmethacrylate also both induced expression of SOCS3, an inhibitor of interleukin-6 signaling. In addition to its effects on interleukin-6 signaling, titanium also profoundly inhibited the interferon-γ-induced activation of STAT1 and the expression of interferon-γ-inducible genes, whereas polymethylmethacrylate had no effect on interferon-γ signaling. Conclusions Titanium inhibits both interferon-γ and interleukin-6 signaling in human osteoclast precursor cells, whereas polymethylmethacrylate bone cement inhibits only the latter. Wear particle inhibition of interleukin-6 specifically involves the activation of p38 mitogen-activated protein kinase and is accompanied by substantial induction of SOCS3, an inhibitor of interleukin-6 signaling. In contrast, titanium inhibition of interferon-γ signaling is not dependent on mitogen-activated protein kinase activation and is accompanied by only modest induction of the interferon-γ inhibitor SOCS1. Clinical Relevance The critical role of wear debris in the development of periprosthetic osteolysis likely involves the inhibition of anti-inflammatory/anti-osteoclastogenic cytokine signaling in addition to the well-established induction of pro-inflammatory mediators. Strategies to augment these “protective” signaling pathways may therefore have therapeutic potential for the treatment of periprosthetic osteolysis.

UNLABELLED The addition of a proximal rough surface finish in the satin finish Spectron stem (Spectron EF) reportedly does not alter its clinical performance. However, we have revised 15 Spectron EF stems because of aseptic loosening and extensive femoral osteolysis at early and intermediate-term followup, raising a question as to its safety. We sought to determine which interface has aseptic failure, the presence of massive femoral osteolysis, and the consequences of loosening at the implant-cement interface in the implant's surface finish. Fifteen patients with aseptic loosening of a proximal rough surface-finished Spectron EF stem at intermediate-term followup (Group A) were compared with seven patients having revisions of the same stem for infection or recurrent dislocation but without loosening (Group B). Radiographs for Group A showed debonding at the cement-implant interface and stem subsidence in 13 hips, and severe femoral osteolysis in seven, including two pathologic periprosthetic fractures. During revision surgery, all 13 subsided stems showed a metallic stained pseudomembrane and metallic shedding with polishing of the stem surface. None of the patients in Group B who had revision surgery had these changes. Aseptic failure of the Spectron EF stem was characterized by debonding, subsidence, and metallic shedding with concomitant massive femoral osteolysis and metallosis, which is similar to conditions reported for loose, rough cemented stems, but has not been reported for the satin finish Spectron stem. LEVEL OF EVIDENCE Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

We report 10 fatigue fractures of a modern, cemented, cobalt chromium alloy stem (Osteonics Omnifit) for total hip arthroplasty occurring between 1995 and 2004. The primary total hip arthroplasties had been performed between 1989 and 1996. The average age at the time of surgery was 54 years (range, 34-70 years), and the average body mass index was 29 (range, 20-38). The time in situ of the prosthesis at the time of fracture averaged 8 years (range, 4-12 years). Intermediate follow-up radiographs before the fracture were available in 7 cases, all of which demonstrated loss of calcar support. Scanning electron microscopy of the fracture surfaces in 3 of the components showed porosity near the initiation site. Metallography of polished and etched cross sections near the fracture surface revealed large grain size. In the presence of a spontaneous onset of thigh pain at intermediate follow-up in patients with this stem, particularly if associated with loss of calcar support, a fatigue fracture should be considered.

Background: The evaluation of periprosthetic osteolysis in patients who have had a total hip arthroplasty is challenging, and traditional imaging techniques, including magnetic resonance imaging and computerized tomography, are limited by metallic artifact. The purpose of the present study was to investigate the use of modified magnetic resonance imaging techniques involving commercially available software to visualize periprosthetic soft tissues, to define the bone-implant interface, and to detect the location and extent of osteolysis. Methods: Twenty-eight hips in twenty-seven patients were examined to assess the extent of osteolysis (nineteen hips), enigmatic pain (five), heterotopic ossification (two), suspected tumor (one), or femoral nerve palsy (one). The results were correlated with conventional radiographic findings as well as with intraoperative findings (when available). Results: Magnetic resonance imaging demonstrated the bone-implant interface and the surrounding soft-tissue envelope in all hips. Radiographs consistently underestimated the extent and location of acetabular osteolysis when compared with magnetic resonance imaging. Magnetic resonance imaging also disclosed radiographically occult extraosseous soft-tissue deposits that were similar in signal intensity to areas of osteolysis, demonstrated the relationship of these deposits to adjacent neurovascular structures, and allowed further visualization of hypertrophic synovial deposits that accompanied the bone resorption in twenty-five of the twenty-eight hips. Conclusions: Magnetic resonance imaging is effective for the assessment of the periprosthetic soft tissues in patients who have had a total hip arthroplasty. While not indicated for every patient who has pain at the site of an arthroplasty, these techniques can be effective for the evaluation of the surrounding soft-tissue envelope as well as intracapsular synovial deposits and are more effective than radiographs for the detection and evaluation of osteolysis, thus aiding in clinical management. Level of Evidence: Diagnostic study, Level III-1 (study of nonconsecutive patients [no consistently applied reference “gold” standard]). See Instructions to Authors for a complete description of levels of evidence.

A 68-year-old patient underwent revision surgery for recurrent dislocation of a ceramic-on-polyethylene uncemented hip arthroplasty implanted 6 months previously. The aluminum oxide femoral head was found to have titanium deposition measuring 5 by 10 mm in an area articulating with the highly cross-linked polyethylene liner. The liner was observed to possess severe scratching produced by articulation with the titanium deposited on the ceramic head. Despite improved scratch resistance of ceramic-bearing surfaces, irregularities introduced by metallic deposition after recurrent dislocation can damage a highly cross-linked polyethylene liner.

Surgical treatment of the patient with rheumatoid arthritis continues to evolve. Synovectomy continues to be an effective palliative procedure, preferred in the early stages of disease. Further investigation into the use of arthroscopic techniques may result in decreased morbidity and a quicker recovery. Total elbow replacement by experienced surgeons employing contemporary designs and surgical techniques is associated with a high degree of success approaching that for total hip and knee replacement.

This article identifies the underlying molecular events responsible for fracture nonunions in a subset of fracture patients. Expression profiling of fracture callus tissue from both uneventful fracture repair and nonunion outcomes showed a decrease of COX-2 expression and an inability to mount an immune response in nonunion fractures. Validation in vitro with Saos-2 osteoprogenitor cell lines showed a decrease in osteogenesis potential after the cells were treated with celecoxib, a COX-2 specific inhibitor and anti-inflammatory agent. This article recapitulates that an initial immune response is crucial to fracture healing and suggests limited usage of COX-2 inhibitors in patients with healing fractures.

Component malalignment can be associated with pain following total knee replacement (TKR). Using MRI, we reviewed 50 patients with painful TKRs and compared them with a group of 16 asymptomatic controls to determine the feasibility of using MRI in evaluating the rotational alignment of the components. Using the additional soft-tissue detail provided by this modality, we also evaluated the extent of synovitis within these two groups. Angular measurements were based on the femoral transepicondylar axis and tibial tubercle. Between two observers, there was very high interobserver agreement in the measurements of all values. Patients with painful TKRs demonstrated statistically significant relative internal rotation of the femoral component (p = 0.030). There was relative internal rotation of the tibial to femoral component and combined excessive internal rotation of the components in symptomatic knees, although these results were significant only with one of the observers (p = 0.031). There was a statistically significant association between the presence and severity of synovitis and painful TKR (p < 0.001).MRI is an effective modality in evaluating component rotational alignment.

Activation of myeloid cells by orthopedic particulate debris is a key event in the pathogenesis of periprosthetic osteolysis and implant loosening after total joint replacement (TJR). Several lines of evidence implicate NACHT, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome-mediated production of interleukin 1 beta (IL-1β) in the pathogenesis of clinical disorders ascribable to foreign particulate materials, including asbestos, silica, and urate crystals. Recent reports indicate that orthopedic polymer products and metallic particulates and ions may activate the same pathway. Here, we investigated the contribution of the NALP3 inflammasome to the pathogenesis of peri-implant osteolysis. Pharmaceutical and genetic perturbations of caspase-1 and inflammasome components were used to assess the role of the NALP3 inflammasome in IL-1β production and osteoclast formation by human monocytes and mouse macrophages in response to polymethylmethacrylate (PMMA) particle phagocytosis. The role of caspase-1 in a mouse calvarial model of particle-mediated osteolysis was assessed using µCT. Phagocytosis of PMMA particles induces caspase-1 dependent release of IL-1β from human monocytes and mouse macrophages. Importantly, using macrophages from mice deficient in components of the NALP3 inflammasome, we show PMMA-induced IL-1β production is strictly dependent on these components. Mice lacking caspase-1, the sole effector of the NALP3 inflammasome, show reduced orthopedic wear particle-induced calvarial osteolysis compared to wild-type controls. Absence of NALP3 inflammasome components fails to alter osteoclast formation in vitro. Our findings identify the NALP3 inflammasome as a critical mediator of orthopedic wear-induced osteolysis and as a viable therapeutic target for the treatment of periprosthetic osteolysis.

RSA is the most accurate technique available to measure implant migration following total hip arthroplasty. Implant migration is an important predictor of long term fixation of uncemented and cemented femoral and acetabular components. Especially with a more recent interest in uncemented fixation continuous migration after 6 months intervals might be evidence of inadequate bone ingrowths. RSA has the benefit of picking up continous migration long before clinical failure will be evident and is therefore considered to be perfectly suited to evaluate new implant designs and implant coatings. It can also be used to evaluate the impact of hard surface bearings including metal-on-metal and ceramic-on-ceramic on bone in-growth and migration of uncemented components. In the future RSA might be an interesting tool to pick up decreased rates of aseptic loosening with the use of computer navigation within short term follow-ups.

Patients with rheumatoid arthritis (RA), an inflammatory arthritis that can destroy joint structures, are often on multiple medications to control disease activity. These medications may have significant toxicities and side effects. Over the course of their lifetime, patients with this disease often require orthopedic procedures, including total joint arthroplasty, and the medications they are taking present management issues specific to the perioperative period. As many of these medications are immunosuppressive, the concern for postoperative infection and delayed wound healing are particularly worrisome. We conducted a review of the available literature pertaining to the perioperative use of the most commonly prescribed medications for RA. Although the existing data directly addressing perioperative complications in orthopedic surgery is sparse, information on relevant complications resulting from the general use of these drugs may be used as a basis for conservative recommendations.

Periprosthetic osteolysis remains the leading complication of total hip arthroplasty, often resulting in aseptic loosening of the implant, and a requirement for revision surgery. Wear-generated particular debris is the main cause of initiating this destructive process. The purpose of this article is to review recent advances in our understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. The most important cellular target for wear debris is the macrophage, which responds to particle challenge in two distinct ways, both of which contribute to increased bone resorption. First, it is well known that wear debris activates proinflammatory signaling, which leads to increased osteoclast recruitment and activation. More recently, it has been established that wear also inhibits the protective actions of antiosteoclastogenic cytokines such as interferon gamma, thus promoting differentiation of macrophages to bone-resorbing osteoclasts. Osteoblasts, fibroblasts, and possibly lymphocytes may also be involved in responses to wear. At a molecular level, wear particles activate MAP kinase cascades, NFκB and other transcription factors, and induce expression of suppressors of cytokine signaling. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties (such as metal-on-metal) should be balanced by awareness that reducing particle size may increase biological activity. Finally, although therapeutic agents against proinflammatory mediators [such as tumor necrosis factor (TNF)] and osteoclasts (bisphosphonates and molecules blocking RANKL signaling) have shown promise in animal models, no approved treatments are yet available to osteolysis patients. Considerable efforts are underway to develop such therapies, and to identify novel targets for therapeutic intervention.

The low wear rates associated with ceramic hip articulations have made them a popular bearing for younger patients. Although few complications have been observed, one report revealed several instances of incomplete seating of the ceramic liner in the metallic shell. We performed a cohort study of consecutive THAs using a ceramic-ceramic bearing. Radiographic analysis showed 50 (7.2%) of the group of 694 hips had evidence of incomplete seating of the liner in the metallic shell. Although we observed no adverse effects at 6 to 12 weeks, we encourage surgeons to carefully assess liner placement in the metal shell at the time of surgery to avoid this unintended consequence and to assess placement at the time of followup so patients can be properly followed when incomplete seating is identified. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Wear-generated particulate debris is the main cause of initiating this destructive process. We present recent advances in understanding of how wear debris causes osteolysis in the aspect of cellular and molecular biological levels. Macrophages, the most important cellular target for wear debris, respond to particle challenge in two distinct ways of pro-inflammatory signaling and inhibition of the protective actions of anti-osteoclastogenic cytokines, finally leading to suppression of osteogenic activity as well as increased osteoclast activity. At a molecular level, such alterations of cellular activities occur through MAP kinase, transcription factors including NF-κB, Wnt/β-catenin signaling and cytokine signaling cascades in various kinds of cells.

Interactions between periprosthetic cells and prosthetic wear debris have been recognized as an important event in the development of osteolysis and aseptic loosening. Although the ability of wear debris to activate pro-inflammatory macrophage signaling has been documented, the full repertoire of macrophage responses to wear particles has not been established. Here, we examined the involvement of alternative macrophage activation and defective osteogenic signaling in osteolysis. Using real-time RT-PCR analysis of periprosthetic soft tissue from osteolysis patients, we detected elevated levels of expression of alternative macrophage activation markers (CHIT1, CCL18), chemokines (IL8, MIP1 alpha) and markers of osteoclast precursor cell differentiation and multinucleation (Cathepsin K, TRAP, DC-STAMP) relative to osteoarthritis controls. The presence of cathepsin K positive multinuclear cells was confirmed by immunohistochemistry. Reduced expression levels of the osteogenic signaling components BMP4 and FGF18 were detected. Expression levels of TNF-alpha, IL-6, and RANKL were unchanged, while the anti-osteoclastogenic cytokine OPG was reduced in osteolysis patients, resulting in elevated RANKL:OPG ratios. In vitro studies confirmed the role of particulate debris in alternative macrophage activation and inhibition of osteogenic signaling. Taken together, these results suggest involvement in osteolysis of alternative macrophage activation, accompanied by elevated levels of various chemokines. Increased recruitment and maturation of osteoclast precursors is also observed, as is reduced osteogenesis. These findings provide new insights into the molecular pathogenesis of osteolysis, and identify new potential candidate markers for disease progression and therapeutic targeting.

The Contour cage introduced in 1999 was designed to improve fixation and provide a surface for bone ongrowth. To determine whether the rates of radiographic loosening and/or revision have been reduced with the Contour design, we retrospectively reviewed the medical records and radiographs of 29 patients (average age, 68.1 years) undergoing 31 acetabular revisions with a Contour cage. The minimum followup was 24 months (mean 30 months, range, 24-58 months). Based on the Paprosky classification, two hips were Type 2B, seven were Type 3A, and 22 were Type 3B. Two hips (7%) were revised for loosening; one of these two was also infected. An additional five hips (16%) had signs of radiographic loosening. The mean Harris hip score improved from 45 to 80; functional scores improved less than the pain scores. Only 14 hips (45%) had an excellent or good clinical result and three of these 14 hips had radiographic signs of loosening; presuming these three hips eventually fail, only 35% of the hips had a good or excellent result. We found an association between number of previous surgeries and radiographic loosening and revision. Our data suggest the Contour cage offers little advantage over other antiprotrusio cages and highlight the substantial limitations of current methods available for treating patients with extensive acetabular bone loss.

The ability of prosthetic wear debris to induce pro-inflammatory responses in macrophages is widely appreciated, but little is known about the molecular mechanisms involved in particle recognition. Specifically, the nature of the cell surface receptors that interact with wear debris is poorly understood. Elucidating the identities of these receptors and how they interact with different types of wear debris are critical to understanding how wear debris initiates periprosthetic osteolysis. We examined the involvement of opsonization, complement receptor 3 (CR3), and scavenger receptor A (SRA), in responses to polymethylmethacrylate (PMMA) and titanium wear particles. Serum dependence of pro-inflammatory responses to PMMA and titanium was tested, and serum proteins that adhered to these two types of particles were identified. Several serum proteins, including known opsonins such as C3bi and fibronectin, adhered to PMMA but not titanium, and serum was required for pro-inflammatory signaling induced by PMMA, but not by titanium. Phagocytosis of PMMA and titanium by macrophages was demonstrated by flow cytometry. Blocking CR3 specifically inhibited phagocytosis of PMMA by macrophages, whereas blocking SRA specifically inhibited titanium uptake. Direct involvement of CR3 and SRA in cell-particle interaction was assessed by expression of these receptors in nonphagocytic HEK293 cells. CR3 specifically induced cell binding to PMMA particles and adhesion to PMMA-coated plates, while SRA specifically induced binding to titanium particles and adhesion to titanium-coated plates. Taken together, these results suggest involvement of opsonization, complement, and integrin receptors, including CR3 and fibronectin receptors, in PMMA action, and an involvement of scavenger receptors in responses to titanium.

In vivo identification of early-stage cartilage degradation could positively impact disease progression in osteoarthritis, but to date remains a challenge. The primary goal of this study was to develop an infrared fiber-optic probe (IFOP) chemometric method using partial least squares (PLS1) to objectively determine the degree of cartilage degradation. Arthritic human tibial plateaus ( N = 61) were obtained during knee replacement surgery and analyzed by IFOP. IFOP data were collected from multiple regions of each specimen and the cartilage graded according to the Collins Visual Grading Scale of 0, 1, 2, or 3. These grades correspond to cartilage morphology that displayed normal, swelling or softening, superficially slight fibrillation, and deeper fibrillation or serious fibrillation, respectively. The model focused on detecting early cartilage degradation and therefore utilized data from grades 0, 1, and 2. The best PLS1 calibration utilized the spectral range 1733–984 cm−1, and independent validation of the model utilizing 206 spectra to create a model and 105 independent test spectra resulted in a correlation between the predicted and actual Collins grade of R2 = 0.8228 with a standard error of prediction of 0.258 with a PLS1 rank of 15 PLS factors. A preliminary PLS1 calibration that utilized a cross-validation technique to investigate the possibility of correlation with histological tissue grade (33 spectra from 18 tissues) resulted in R2 = 0.8408 using only eight PLS factors, a very encouraging outcome. Thus, the groundwork for use of IFOP-based chemometric determination of early cartilage degradation has been established.

Introduction: Advantages of MIS TKR include less postoperative pain and improved early range of motion. However, all studies to date are either retrospective, or at best prospective comparisons with matched controls and as such fail to control for patient expectations/placebo effect and in many cases selection bias. The purpose of this study was to determine whether the MIS midvastus approach to TKR resulted in quantitative differences in quadriceps muscle strength and the previously cited advantages.

Tibiotalar dislocation without fracture is an unusual injury. Seventy-three cases have been reported in the literature. Closed posteromedial dislocation of the tibiotalar joint without fracture or diastasis is a very rare phenomenon. Eight cases have been reported. A case of this unique injury is presented, along with a literature review of purely ligamentous ankle dislocations. The proposed mechanism and classification of these injuries are summarized.

The purpose of this study was to determine whether the mini-midvastus approach to total knee arthroplasty (TKA) results in differences in quadriceps muscle strength as well as previously cited advantages in a double blind prospective randomized trial. Twenty-seven patients (54 TKAs) scheduled for bilateral TKA were randomized to undergo mini-midvastus approach on one knee and standard approach on the other. Incision lengths were the same. Postoperative strength was determined by isokinetic and isometric peak torque testing. Range of motion, pain Visual analog scale, side-preference, and gait analysis were assessed preoperatively and postoperatively. The only significant difference in strength testing was increased isokinetic and isometric extension torque at 3 weeks postoperatively for the mini-midvastus approach. No differences between the mini-midvastus and standard approach were observed for stride length, stance time, pain Visual analog scale, or knee range of motion. The mini-midvastus approach has limited benefit compared to the standard approach for TKA.

Radiographs were studied of 91 feet in 62 patients with the diagnosis of bunionette and no prior bunionette or hallux valgus operations. Various radiologic measurements were compared to a matched control group with no bunionette symptoms or previous forefoot operations. The bunionette group had a significantly increased metatarsophalangeal 5 angle, intermetatarsal 4–5 angle, and intermetatarsal 1–2 angle compared to the control group. Bunionettes were not commonly associated with lateral bowing of the fifth metatarsal or with an increased fifth metatarsal head width. Symmetry was noted between symptomatic and opposite asymptomatic feet, with the exception of an increased intermetatarsal 4–5 angle in the symptomatic feet.