Bryan J. Nestor

Magnetic Resonance Imaging After Total Hip Arthroplasty: Evaluation of Periprosthetic Soft Tissue

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.

The Central Role of Wear Debris in Periprosthetic Osteolysis

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.

Wear debris inhibition of anti-osteoclastogenic signaling by interleukin-6 and interferon-γ : Mechanistic insights and implications for periprosthetic osteolysis

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-gamma. 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-gamma. Interleukin-6 signaling was determined by measuring the activation of STAT3 signal transduction with use of immunoblotting and electrophoretic mobility shift assays. Interferon-gamma 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-gamma-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-gamma-induced activation of STAT1 and the expression of interferon-gamma-inducible genes, whereas polymethylmethacrylate had no effect on interferon-gamma signaling. CONCLUSIONS Titanium inhibits both interferon-gamma 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-gamma signaling is not dependent on mitogen-activated protein kinase activation and is accompanied by only modest induction of the interferon-gamma inhibitor SOCS1.

Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation

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.

Perioperative Management of Medications Used in the Treatment of Rheumatoid Arthritis

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.

Influence of total hip design on dislocation: a computer model and clinical analysis.

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.

A Chemometric Analysis for Evaluation of Early-Stage Cartilage Degradation by Infrared Fiber-Optic Probe Spectroscopy

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.

Mini-midvastus vs standard medial parapatellar approach: a prospective, randomized, double-blinded study in patients undergoing bilateral total knee arthroplasty.

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.

Acetabular revision with the Contour antiprotrusio cage: 2- to 5-year followup.

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.Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

MRI evaluation of rotational alignment and synovitis in patients with pain after total knee replacement

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.