Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis. In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition. Cite this article: Bone Joint J 2013;95-B:1021–5

Highly crosslinked polyethylene (XLPE) was introduced to decrease peri-prosthetic osteolysis related to polyethylene wear, a major reason for revision of total hip arthroplasty. There are few reports of wear and osteolysis at 10 years post-operatively. We asked the following questions: (1) What are the linear and volumetric wear rates of one remelted XLPE at 10–14 years using the Martell method? (2) What is the relationship between volumetric wear, femoral head size, and osteolysis? (3) What is the incidence of osteolysis using conventional radiographs with Judet views and the Martell method?. Methods We evaluated a previously reported cohort of 84 hips (72 patients) with one design of an uncemented acetabular component and one electron-beam irradiated, remelted XLPE at a mean follow-up of 11 years (range 10 to 14 years). Measurements of linear and volumetric wear were performed in one experienced laboratory by the Martell method and standard radiographs, with additional Judet views, were used to detect peri-prosthetic osteolysis. Statistical analysis of wear and osteolysis compared to head size was performed. Results The mean linear wear rate by the first-to-last method was 0.024 mm/year (median, 0.010 mm/year) and the mean volumetric wear rate by this method was 12.2 mm. 3. /year (median, 3.6 mm. 3. /year). We found no association between femoral head size and linear wear rate. However, there was a significant relationship between femoral head size and volumetric wear rates, with 36/40 mm femoral heads having significantly higher volumetric wear (p=0.02). Small osteolytic lesions were noted in 12 hips (14%), but there was no association with head size, acetabular component position, or linear or volumetric wear rates. Conclusion This uncemented acetabular component and this particular remelted XLPE had low rates of linear and volumetric wear. Small osteolytic lesions were noted at 10 to 14 years, but were not related to femoral head size, linear or volumetric wear rates

Aims: Given that all previous reports on the increased-crystalinity, increased modulus of elasticity, yield strength and density Hylamer polyethylene have been based on observations on uncemented metal-backed acetabular cups, the aim of the present study is to investigate the rate of wear of a cemented Hylamer UHMWPE acetabular cup. Methods: 36 consecutive cases of THA (mean age: 54.7 years) using a cemented Hylamer UHMWPE acetabular cup and a cemented femoral stem were prospectively followed-up with yearly radiographs for an average period of 54.4 months. Two-dimensional femoral head penetration was determined from AP pelvic radiographs, using computeraided uniradiographic methodology. Multiple regression analysis was used to identify all predictor variables that may account for increased average linear and calculated volumetric wear (Kabo’s formula), as well as for increased total area of peri-prosthetic osteolysis on the femoral and acetabular sides. Results: The average linear wear rate was 0.35 mm/year (SD 0.12) with a significantly high average linear wear rate during the initial (‘wear-in’) period (approximately 12–18 months). The average total volumetric wear was calculated to 764.4 mm3 and the average volumetric wear rate to 169.8 mm3/year. Significant osteolysis was seen in an average of 1.5 (range: 0 to 7) out of the 7 Gruen zones on the femoral side and an average of 1 (range: 0 to 3) out of the 3 Charnley-Delee zones on the acetabular side. Conclusions: Increased rate of linear wear and a high rate of peri-prosthetic osteolysis have been observed in the early results of our series of cemented Hylamer UHMWPE acetabular cups

Introduction: Electron beam irradiated highly cros-slinked polyethylene has been used in total hip arthroplasty for over 8 years. Due to its low wear characteristics, the use of femoral heads that are greater than 32mm in diameter is now available, allowing for an increase in range of motion and increased stability against dislocation when necessary. The purpose of this study is to provide a summary report on the radiographic analysis of the longest term data available on primary THR patients receiving highly cross-linked polyethylene and to compare the results of two methods of measuring femoral head penetration. Methods: Three prospective clinical studies involving electron beam irradiated highly cross-linked polyethylene have been initiated at our center. To date, the results of: 200 hips with a minimum of 6 year follow-up with conventional sized femoral heads (primarily 28 and 32mm); 45 hips with minimum 5 year follow-up with larger sized femoral heads (primarily 36 and 38mm); and 30 hips with 5 year follow-up enrolled in a Radiostereometric analysis (RSA) study (15 patients with 28mm and 15 patients with 36mm diameter femoral heads); were available for this summary report. Data from patient administered questionnaires (Harris Hip score, UCLA activity score, and WOMAC), radiographic review, and wear analysis using RSA or the Martell Hip Analysis Suite™. In addition, for comparative purposes, wear was measured in a subset of patients using the Devane Polyware™ program. Results: All hips had good clinical outcome at longest follow-up regardless of which femoral head size was used. There were no revisions due to polyethylene wear and no evidence of peri-prosthetic osteolysis. In general, after the bedding in period, there was no significant increase in femoral head penetration regardless of head size. For RSA, the wear rate for the 28mm femoral head group was 0.05±0.02 while the 36mm femoral head group was 0.03±0.02, p=0.13. For the Martell analysis, the average steady-state wear rate was −0.002 ± 0.01 mm per year and −0.026 ± 0.13 mm per year for 28mm and 32mm head sizes, respectively, p=0.62. There was no correlation between wear and time in situ or femoral head size for any of the clinical studies. In comparing the Martell and Devane programs, the total average wear rates were significantly different, 0.07±0.05 and 0.03±0.06mm/year respectively, p=0.01. However, when the absolute values of the Martell results were used, there was no difference, p=0.22. Conclusion: The mid-term follow-up of a large group of primary THR patients receiving highly cross-linked polyethylene components have shown no problems related to the new bearing material. Extremely low wear and lack of peri-prosthetic osteolysis are encouraging results requiring further long-term study

Introduction. The first highly crosslinked and melted polyethylene acetabular component for use in total hip arthroplasty was implanted in 1998. Numerous publications have reported reduced wear rates and a reduction in particle induced peri-prosthetic osteolysis at short to mid-term follow-up. The purpose of this study was to re-assemble a previous multi-center patient cohort in order to evaluate the radiographic and wear analysis of patients receiving this form of highly crosslinked polyethylene articulating against 32mm femoral heads or less at a minimum of 13 years follow-up. Methods. Inclusion criteria for patients was a primary THR with femoral heads 32mm or less and a minimum 13 year follow-up. 139 hips have been enrolled with an average follow-up of 13.7 years (13–16), 80 females (57%). Wear analysis was performed using the Martell Hip Analysis software. Radiographic grading was performed on the longest follow-up AP hip films. The extent of radiolucency in each zone greater than 0.5mm in thickness was recorded along with the presence of sclerotic lines and osteolysis. Results. Wear analysis: Using the average of the slopes of the individual regression lines, the wear rate was 0.006±0.033mm/yr. Using the early to latest film method, the wear rate was 0.003±0.056mm/yr. Radiographic analysis: Acetabular side: the greatest incidence of radiolucency occurred in zone 1 at 21%; sclerotic lines had a less than 2% incidence in any of the 3 zones; there was no identified osteolysis. Femoral side: the incidence of radiolucencies was limited to zone 1, 2%; sclerotic lines were rare in any zone, maximum in zone 3, 4%; there was no identified osteolysis. Conclusion. The wear of this form of irradiated and melted highly crosslinked polyethylene remained at levels lower than the detection limit of the software at minimum 13 year follow-up and there was no identified osteolysis

The most frequent cause of failure after total hip replacement in all reported arthroplasty registries is peri-prosthetic osteolysis. Osteolysis is an active biological process initiated in response to wear debris. The eventual response to this process is the activation of macrophages and loss of bone. Activation of macrophages initiates a complex biological cascade resulting in the final common pathway of an increase in osteolytic activity. The biological initiators, mechanisms for and regulation of this process are beginning to be understood. This article explores current concepts in the causes of, and underlying biological mechanism resulting in peri-prosthetic osteolysis, reviewing the current basic science and clinical literature surrounding the topic

INTRODUCTION. The hip arthroplasty implant is currently growing up both in orthopedic and trauma practice. This increases the frequency of prosthesis revision due to implant loosening often associated with periprosthetic osteolysis that determine the failure and lead to a loss of bone substance. Nowadays there are numerous biotechnologies seeking to join or substitute the autologous or omologous bone use. These biotechnologies (mesenchymal stromal cells, growth factors and bone substitutes) may be used in such situations, however, the literature doesn't offer class 1 clinical evidences in this field of application. MATERIALS AND METHODS. We performed a literature review using the universally validated search engines in the biomedical field: PubMed / Medline, Google Scholar, Scopus, EMBASE. The keywords used were: “Growth Factors”, “Platelet Rich Plasma”, “OP-1”, “BMP”, “BMP-2”, “BMP-7”, “Demineralized Bone Matrix”, “Stem Cell”, “Bone Marrow”, “Scaffold”, “Bone Substitutes” were crossed with “hip”, “revision”, “replacement” / “arthroplasty”, “bone loss” / “osteolysis.”. RESULTS. The search led to 321 items, of these were considered relevant: as regards the growth factors 21 articles related to in vivo animal studies and 2 articles of human clinical use of BMPs and 1 single article on the use of PRP; as regards the mesenchymal stromal cells 2 items of application in animals; as regards the use of bone substitutes we have analyzed a review of this application. DISCUSSION. The use of biotechnologies in hip prosthetic revisions has produced conflicting results: autologous growth factors (PRP) have definitely been proven effective in maxillofacial surgery, in animal studies the results of BMPs are inconsistent with articles that validate their use and others that don't recommend it. Clinical application has demonstrated, today, the limited use of BMP-7 in revisions with even an increased risk of early re-mobilization, PRP appears to be rather effective only in the early stages of peri-prosthetic osteolysis. The mesenchymal cells can increase the chances of recovery and integration of the grafts but an important variable is the number of cells that are still alive after the impaction of the graft which affects their vitality. The bone substitutes appear to be safe and very useful, particularly if applied in order to implement the omologous bone, which is still the most scaffolds used in this surgery. CONCLUSIONS. The systematic review of the literature has shown an important lack of clinical studies regarding the use of biotechnologies for prosthetic revisions. It is therefore difficult to draw guidelines that regulate the application, prospective randomized clinical studies are therefore needed to validate its effectiveness

INTRODUCTION. The hip arthroplasty implant is currently growing up both in orthopedic and trauma practice. This increases the frequency of prosthesis revision due to implant loosening often associated with periprosthetic osteolysis that determine the failure and lead to a loss of bone substance. Nowadays there are numerous biotechnologies seeking to join or substitute the autologous or omologous bone use. These biotechnologies (mesenchymal stromal cells, growth factors and bone substitutes) may be used in such situations, however, the literature doesn't offer class 1 clinical evidences in this field of application. MATERIALS AND METHODS. We performed a literature review using the universally validated search engines in the biomedical field: PubMed / Medline, Google Scholar, Scopus, EMBASE. The keywords used were: “Growth Factors”, “Platelet Rich Plasma”, “OP-1”, “BMP”, “BMP-2”, “BMP-7”, “Demineralized Bone Matrix”, “Stem Cell”, “Bone Marrow”, “Scaffold”, “Bone Substitutes” were crossed with “hip”, “revision”, “replacement” / “arthroplasty”, “bone loss” / “osteolysis.”. RESULTS. The search led to 321 items, of these were considered relevant: as regards the growth factors 21 articles related to in vivo animal studies and 2 articles of human clinical use of BMPs and 1 single article on the use of PRP; as regards the mesenchymal stromal cells 2 items of application in animals; as regards the use of bone substitutes we have analyzed a review of this application. DISCUSSION. The use of biotechnologies in hip prosthetic revisions has produced conflicting results: autologous growth factors (PRP) have definitely been proven effective in maxillofacial surgery, in animal studies the results of BMPs are inconsistent with articles that validate their use and others that don't recommend it. Clinical application has demonstrated, today, the limited use of BMP-7 in revisions with even an increased risk of early re-mobilization, PRP appears to be rather effective only in the early stages of peri-prosthetic osteolysis. The mesenchymal cells can increase the chances of recovery and integration of the grafts but an important variable is the number of cells that are still alive after the impaction of the graft which affects their vitality. The bone substitutes appear to be safe and very useful, particularly if applied in order to implement the omologous bone, which is still the most scaffolds used in this surgery. CONCLUSIONS. The systematic review of the literature has shown an important lack of clinical studies regarding the use of biotechnologies for prosthetic revisions. It is therefore difficult to draw guidelines that regulate the application, prospective randomized clinical studies are therefore needed to validate its effectiveness

Osteoclasts are cells that resorb bone. They derive from haemopoietic precursors in the presence of Macrophage-Colony Stimulating Factor (M-CSF) and the osteoclast growth factor, Receptor Activator of Nuclear Factor–kB Ligand (RANKL). Tumour Necrosis Factor-a (TNF-a) and M-CSF has been shown to form mature osteoclastic bone resorption in vitro murine cultures in the absence of RANKL. The aim of this study was to investigate the mechanism of action of the pro-inflammatory cytokine Tumour Necrosis Factor-a (TNF-a) with respect to osteoclastic bone resorption. Development of osteoclasts was performed using an in vitro assay of healthy human peripheral blood mononuclear culture (PBMNC) in the presence of M-CSF and RANKL. In the same cultures RANKL was replaced by TNF-a over a wide range of concentrations. Osteoclasts were generated in the presence of M-CSF, TNF-a and RANKL from human PBMNC. However, in the same experiments M-CSF and TNF-a in the absence of RANKL failed to support human osteoclast formation. Aseptic loosening and osteolysis are considered the main long-term complications of hip arthroplasty. Pathogenesis of peri-prosthetic osteolysis is multifactorial and both biological and mechanical factors are important. TNF-a is thought to be involved in orthopaedic implant oste-olysis induced by prosthesis-derived wear particles. The final osteolytic step is undertaken mainly by osteoclasts. This is the first report showing that TNF-a and M-CSF in the absence of RANKL in human PBMNC is not capable of inducing osteoclast formation. TNF-a therefore may increase peri-prosthetic loosening by enhancing the activity of the mature osteoclast

Background: This report presents the long term (over 20 years) experience with the use of a grit-blasted, press-fit femoral prosthesis. Methods: The first 300 consecutive primary THA procedures using a collarless, three-dimensional tapered, straight, titanium alloy stem with a grit-blasted surface (performed in 299 patients) were evaluated up to twentytwo years. A cementless all-polyethylene socket in 80 percent of the cases, were used. Radiographic evaluation, performed by an independent observer using a zonal analysis method, included assessment of component migration, Engh’s implant-bone femoral fixation score, implant-bone demarcations, and periprosthetic osteolysis. The average duration of long-term radiographic follow-up was 12.6 years (range; 10 to 16 years). Results: At last examination only five hips were lost to follow-up and 84 patients were deceased. The femoral revision rate was 7 percent (two hips for aseptic loosening, five hips for septic loosening, and twelve hips with osseointegrated stems for severe progressive femoral osteolysis) and the acetabular revision rate was 28% (revised for either socket migration or progressive peri-acetabular osteolysis or both). Survivorship, based on any revision (femoral or acetabular) was 89% at ten years and 65% at twenty years; survivorship of the femoral component was 95% at ten years and 89% at twenty years. The incidence of femoral periprosthetic osteolysis, was 47%, with 5% of distal endosteal osteolysis. Radiographic femoral implant-bone fixation was stable, bone-ongrowth in 97%; stable, fibrous-fixation in 1%. Conclusions: The grit-blasted, press-fit, collarless, tapered femoral component continued to perform well clinically and radiographically up to twenty years of follow-up despite the challenging environment of peri-prosthetic osteolysis associated with the acetabular component design. This implant is still in use virtually without design modifications. This study demonstrates the durability of the results of the grit-blasted femoral component and indicates that such an implant offers a viable alternative for fixation without bone cement

INTRODUCTION. The advantages of large diameter metal on metal total hip arthroplasty (MoM THA) and hip resurfacing arthroplasty are decreased wear rate, preservation of bone stock, anatomical restoration and enhanced stability. Large amounts of metal wear particles and metal ions are released which may induce adverse reactions including local soft tissue toxicity, hypersensitivity reactions, bone loss and risk of carcinogenesis. Aseptic loosening can be the result of a peri-prosthetic osteolysis generated as a result of a biological response to particulate wear debris. No reports in the literature exist as to whether circulating levels of Chromium (Cr) and Cobalt (Co) decrease upon removal of a symptomatic large diameter MoM implant or whether levels remain high due to the effect of metal ions debris left behind in the soft tissues after revision surgery. PATIENTS AND METHODS. Between June 2006 and June 2009 we undertook 44 revision surgeries of both large head MoM THAs (femoral head diameter 38mm) and metal-on-metal hip resurfacings for suspected metallosis. Mean time from original implant to revision was 4 years, 8 months (1yr 4mo–7yr 9mo). The mean follow up evaluation was 2 years and 2 months (1yr 2mo–4 years). Blood samples were taken for whole blood Cr and serum Co according to a recognised protocol and compared with reference levels indicated by the Medicines and Healthcare Regulatory Agency recommendation of less than 7ppb for Cr (130nM/L) and Co (119nM/L). RESULTS. 42 patients were found to have histological evidence of either metal allergy, metal toxicity or foreign body reaction. 2 patients had evidence of infection with no features of metal reaction. 3 patients suffered early dislocation requiring closed reduction. 1 patient had infective complications necessitating Girdlestones. 11 patients were lost to follow up, 8 patients were diagnosed pre operatively on Co and Cr levels in urine or synovial fluid aspirate alone. 23 patients had pre revision blood or serum metal ion level results available for direct comparison. Median serum Co level pre revision was 176.6nM/L, falling post revision to 5.1nM/L (p=<0.001∗). The median whole blood Cr level pre revision was 117nM/L and 19nm/L post revision (p=<0.001∗). Mean Oxford Hip Score was 23.7. DISCUSSION. This study demonstrates that at greater than one year post removal of a large diameter MoM hip implant for the indication of symptomatic metallosis or metal hypersensitivity, metal ion levels fall to almost normal levels and that outcome of revision surgery in terms of patient satisfaction is not adversely affected

There is a renewed interest in unicompartmental knee arthroplasty. The present report describes the minimum ten-year results associated with a – unicompartmental knee arthroplasty design that is in current use. Sixty-two consecutive unicompartmental knee arthroplasties that were performed with cemented modular Miller-Galante implants in 51 patients were studied prospectively both clinically and radiographically. All patients had isolated unicompartmental disease without patellofemoral symptoms. No patient was lost to follow-up. Thirteen patients (13 knees) died after less than 10 years of follow-up, leaving 38 patients (49 knees) with a minimum of 10 years of follow-up. The average duration of follow-up was 12 years. The mean Hospital for Special Surgery knee score improved from 55 points preoperatively to 92 points at the time of the final follow-up. Thirty-nine knees (80%) had an excellent result, six (12%) had a good result, and four (8%) had a fair result. At the time of final follow-up, 39 knees (80%) had flexion to at least 120 degrees. Two patients (two knees) with well-fixed components underwent revision to total knee arthroplasty, at seven and 11 years, because of progression of patello-femoral arthritis. At the time of the final follow-up, no component was loose radiographically and there was no evidence of peri-prosthetic osteolysis. Radiographic evidence of progressive loss of joint space was observed in the opposite compartment of nine knees (18%) and in the patello-femoral space of seven knees (14%). Kaplan-Meier analysis revealed a survival rate of 98.0% +/−2.0% at ten years and of 95.7% +/− 4.3% at 13 years, with revision or radiographic loosening as the end point. The survival rate was 100% at 13 years with aseptic loosening as the end point. After a minimum duration of follow-up of 10 years, this cemented modular uni-compartmental knee design was associated with excellent clinical and radiographic results. Although the 10 year survival rate was excellent, radiographic signs of progression of osteoarthritis in the other compartments continued at a slow rate. With appropriate indications and technique, this uni-compartmental knee design can yield excellent results into the beginning of the second decade of use

Introduction: Peri-prosthetic osteolysis due to wear has been acknowledged as a major challenge to long-term survival of hip arthroplasty and this has led to a search for alternative articular bearing couples. We present our experience with metal-on-metal (Metasul. ®. ) articulation with a minimum patient follow-up of 5 years. Materials and methods: 193 patients (215 hips) were reviewed; 187 (209 hips) had a follow-up of ≥ 5 years. Hip scores were completed and radiographs performed at follow-up visits and data was entered prospectively into software (orthocom) designed by Sulzer Ltd.. Serial radiographs were reviewed retrospectively along with hospital notes and the database. Results: mean age was 70 (± 7.46) years (range 47–86 years). Female: male was 143:44. Most common pre-operative diagnoses were: osteoarthritis (147) and intra-capsular hip fracture (22). Mean pre-operative HHS was 39.7 (±15.7) and the corresponding pain score was 13.4 (±8.49). The average post-operative scores were 89.5, 87.3, 88.4 and 85.8 at 1 year, 3 years, 5 years and final follow-up respectively. The corresponding pain scores were 42.7, 41.98, 42.1 and 41.94. Implant survival for the cohort as a whole was 95.5% at 12 years (ci: 88%–100%). Survivorship for the Weber Metasul cup was 93.4% at 12 years (ci: 82.7%–100%) and for armor cup was 100% at 11 years. Complications included: dislocations (7), periprosthetic fractures (8), deep infection- early (3) & late (3), aseptic loosening (cup) (2) & heterotopic ossification (9). There were no untoward systemic complications with regards to metal ion release. Discussion: We believe that second generation metal-on-metal implants (Metasul. ®. ) with improved design and better lubrication show better survival with regards to aseptic loosening and reduction in osteolysis in the medium-term. Concerns regarding metal ion and metal particle release remain theoretical but are kept under constant review

Peri-prosthetic bone loss may contribute to aseptic loosening after THA. The aims of this randomised controlled trial extension study were to study the effect of pamidronate therapy on Peri-prosthetic bone mineral density (BMD) and Peri-prosthetic osteolysis over 5 years after primary THA. 50 patients were enrolled in the study in 1998. All received a hybrid THA (Ultima-TPS stem, Plasmacup) for osteoarthritis. Subjects were randomised to receive either 90mg of pamidronate or placebo by intravenous infusion on the 5. th. post-operative day. At 5 years 36 patients (41 Hips: placebo n=21, pamidronate n=20) returned for measurement of BMD and clinical and plain radiographic assessment. Five patients had died and nine had withdrawn from the study. The effect of pamidronate in maintaining femoral bone mass in the region of the calcar previously reported at 2 years was maintained at 5 years (Gruen zone 6 pamidronate versus placebo ANOVA P=0.038; Gruen zone 7 ANOVA P=0.048). No differences in pelvic BMD were found between treatment groups at 5 years. Harris hip scores used to evaluate clinical outcome did not show any significant difference between the 2 groups over the 5-year period. (Mann Whitney p> 0.05). Isolated expansile osteolytic lesions were identified on AP radiographs of the hip at 5 years in 4 patients (2 placebo, 2 pamidronate; P> 0.05). One patient had a 5x9mm lytic lesion in the region of the femoral calcar, and 3 patients had pelvic lytic lesions in the region of the acetabular dome (largest measuring 20x10mm). Single-dose peri-operative pamidronate therapy preserves femoral calcar bone mass over a 5 year period after THA. However, although the number of subjects with osteolysis is small, we have seen no difference in the rate of osteolytic lesions between treatment groups. Long term study of this patient group is required to examine the rate of aseptic loosening between the treatment groups

Introduction: By compromising bone structure, peri-prosthetic osteolysis may increase the risk of fracture and/or aseptic loosening of components leading to revision surgery. Our purpose was to develop a reproducible rabbit model of periprosthetic osteolysis and observe the effects of implant type and fixation on the latency to onset and size of the osteolytic lesions. Methods: Thirty-seven New Zealand White rabbits (71 knees) underwent knee arthrotomy and placement of cylindrical intramedullary stainless steel or polymethylmethacrylate (PMMA) implants. Each knee contained both a metallic and PMMA implant in either the femur or tibia that communicated with a common synovial space. A suspension of polyethylene particles (size < 4.5 um and concentration of 1-5 x 106 particles/ul) was injected into each knee at two-week intervals for ten weeks to induce osteolysis. Serial radiographs were taken at 4, 8, 14, 18, and 22 weeks postoperatively to document the progression of osteolysis. Statistical analysis was performed utilizing a two-tailed, unpaired t-test and a Mantel-Cox test with the level of significance set a p < 0.05. Results: Radiographic analysis revealed that 96.9% of the stainless steel implants had evidence of osteolysis by 22 weeks compared to 22.9% of the PMMA implants (p< 0.001). The earliest onset of lesions in the metal implant group occurred at four weeks compared to 14 weeks in the PMMA group. We also found the area and volume of the osteolytic lesions to be significantly larger in the metal implants when compared to the implants composed of PMMA (p < 0.01). Conclusions: Onset of osteolysis around metal implants occurred in a significantly shorter period of time and more frequently when compared to implants composed of PMMA. Also, the area and volume of the osteolytic lesions around the metal implants was found to be significantly larger than those of the PMMA. We concluded that relative material effects on osteoclast induced bone resorption and differences in ease of transport of particulate debris along metallic compared to PMMA surfaces may account for observed differences in frequency and severity of osteolytic lesions

Improved cement technique by interposing less than two layers of hydroxyapatite (HA) granules between bone and bone cement at the cementing (Interface Bio-active Bone Cement : IBBC) have been performed in total knee arthroplasty (TKA) since 1987. We performed IBBC technique in 153 knees (130 patients) in TKA from 1987 to 1993. One hundred and forty knees (120 patients) could be followed up clinically and radiologically. Follow up rate was 91.5%. A mean follow-up period was 9.5 years (6 to 13 years) after surgery. As a control, clinical results of TKA with conventional cementing (Non-IBBC) which were operated in 44 knees (44 patients) in 1986 were used. In IBBC cases, radiolucent lines on the tibial components were seen 7.1%, 2.9%, 1.4%, 3.6%, 0%, 0% and 0% at Zone ‡T to ‡Z of the anteroposterior view, while in Non-IBBC cases, 40.9%, 13.6%, 9.1%, 27.3%, 11.4%, 4.5% and 13.6% at Zone ‡T to ‡Z, respectively. In IBBC cases peri-prosthetic osteolysis of the tibial components were seen in three knees (2.1%), while 29.5% in Non-IBBC cases. Aseptic loosening of the tibial component was only one case (0.7%) in IBBC cases, while 9.1% in Non-IBBC cases. In IBBC, bone cement bound to HA mechanically immediately after surgery and HA granules bound to the bone physicochemically after bone ingrowth into the spaces around the HA granules. In Non-IBBC, spaces will appear between bone and bone cement due to osteoporosis and/or atrophy after long years. However, in IBBC, bone and bone cement will contact by interposing HA forever due to osteoconductive effect of HA. In conclusion, the IBBC has significantly reduced the incidence of radiolucent lines and periprosthetic osteolysis in TKAs. IBBC is a method combining the advantage of cementless HA coating and bone cement

Highly cross-linked polyethylene (HXLPE) is one of the most widely utilized bearing surfaces for total hip arthroplasty (THA). The first patients to receive XLPE will be 10 years post-op as of December 31, 2008. The purpose of this study is to report the long-term clinical and radiographic outcomes of patients implanted with HXLPE. A group of 247 primary total hip replacements (224 patients) using HXLPE liners (Longevity or Durasul, Zimmer Inc.) with 22, 26, 28, or 32mm femoral heads were implanted between 1999 and 2001. Clinical evaluation measures included the Harris hip, EQ-5D, SF-36 functional scores, and UCLA activity scores. In addition to plain radiograph assessment, the computerized Martell method was used to measure head penetration over time. A matched group of 241 primary total hip replacements (201 patients) with the same head sizes using conventional polyethylene (PE) with a minimum of 7 years follow-up was used as a Martell method control group. The steady state penetration rate was defined as the slope of the linear regression line of the plot of head penetration from the 1 year film to each subsequent film to discount the early bedding-in process. A student’s t-test was used to compare wear rates between head sizes in each group, and a repeated-measures mixed model ANOVA was used to compare the groups for the 28mm head size. There were no osteolytic lesions around the cup or stem, and no revisions were performed for polyethylene wear or liner fracture. Clinical outcome scores were averaged: Harris Hip 88.1±11.97, EQ-5D 74.0±27.0, SF-36 physical activity scores 53.3±8.4, SF-36 mental score 46.9±11.1, and UCLA activity 6.4±2.1. The steady state wear of the conventional polyethylene patients increased with time for both 26 and 28mm head sizes (0.144 and 0.127mm/year, respectively). No significant difference was found between the head sizes coupled with conventional polyethylene (p=0.14). Femoral head penetration in the highly cross-linked polyethylene did not increase over time after the first year. The steady state wear rates of HXLPE liners with 28mm or 32mm femoral heads were not significantly different than a slope of zero (p=0.54 for both head sizes). Clinical follow-up results are typical of a primary THR patient population, and the radiographic results are excellent with no signs of peri-prosthetic osteolysis. Patients with PE show wear rates that are significantly different than zero indicating significant wear of the material. Conversely, patients with HXLPE display no measureable wear at 7–9 years as the wear rates were within the error detection of the Martell method. This long-term clinical and radiographic follow-up study for this new bearing material shows excellent clinical outcomes with very low in vivo wear

Aims

Total knee arthroplasty (TKA) is a common and safe orthopaedic procedure. Zimmer Biomet's NexGen is the second most popular brand of implant used in the UK. The primary cause of revision after the first year is aseptic loosening. We present our experience of using this implant, with significant concerns around its performance with regards early aseptic loosening of the tibial component.

Introduction: Our group has previously reported on microarray gene expression profiling of failed aseptic and septic THRs. The data obtained from the Affymetrix DNA chips suggested a range of 21 differentially expressed genes between the tissue samples obtained from the control and study patients with failed aseptic THRs. The variation in expression that was demonstrated did not suggest that the basis of the local tissue reaction that occurs in aseptic loosening of THR is primarily inflammatory in nature. In order to validate these results we have performed quantitative real-time polymerase chain reaction (RT-PCR) to analyse the transcriptional levels of genes expression in the samples used in our original study and to formulate a hypothesis of how these candidate genes can be related to aseptic join loosening. Methods: 3 control and 6 aseptic samples of peri-prosthetic membrane were subjected to RNA extraction. RNA quality analysis and quantification were performed. SYBRâ Green I real time quantitative PCR (RT qPCR) assays were designed using Primer Express [Applied Biosystems] and BLAST searching the resulting sequences. The comparative method for quantitation of gene expression levels, which utilizes arithmetic formulas to give the similar results to those achieved with standard curves, was utilised to validate the cDNA microarray data. Results: We were able to devise successful quantitative real-time PCR for 15 of the 21 candidate genes plus the reference gene GAPDH. The genes coding for complement component C4B, Osteonectin , ATP2A2 (an ATPase linked to the regulation of adhesion, differentiation and proliferation in tissue that expresses this gene such as bone) and Phospholipase2A, were all found to be under-expressed whereas SLC2A5 (a solute carrier that can facilitate glucose/fructose transport)and NPC1 (intimately involved in cholesterol and glycolipid trafficking and inversely related to PLA2-mediated release of eicosanoids such as PGE2) were found to be over-expressed. Conclusions: The data from our gene expression and RT-PCR studies have suggested novel pathways that may be intimately involved in the development of peri-prosthetic osteolysis and aseptic loosening that are distinctly different from the currently accepted theory of a proinflammatory cytokine cascade initiated by tissue reaction to particulate wear debris. These include possible alteration in both extra- and intracellular Ca2+ metabolism together with a possible effect upon extra-cellular matrix function. Altered lipid metabolism may also be evident and in particular decreased eicosanoid production. Intriguingly, the pattern of gene expression that is seen our studies would appear to be quite different than that seen in synovial inflammatory arthritidies such as rheumatoid and osteo-arthritis and suggests that previous studies that has used these pathological mechanisms as comparisons or controls may be flawed

Aseptic loosening is generally associated with the presence of wear particle-associated macrophages in the pseudomembrane commonly formed around failed prosthetic implants. The extent of the macrophage response evoked by the wear particles has been shown to correlate with the amount of periprosthetic osteolysis. Numerous studies have shown that wear particle-associated macrophages contribute to osteolysis by (i) releasing inflammatory cytokines and/or (ii) differentiating into bone resorbing osteoclasts. Although macrophages and macrophage polykaryons are the main inflammatory cells found in periprosthetic tissues, numerous fibroblasts are also present in the connective tissue pseudomembrane. The recently identified molecule, RANKL has been shown to play a central role in the osteoclast formation and bone resorption observed in aseptic loosening. We have shown that arthroplasty macrophages, which express RANK, the receptor for RANKL, are capable of osteoclast differentiation; this process is inhibited by osteoprotegerin (OPG), the soluble decoy receptor for RANKL. As fibroblasts are known to express RANKL, the aim of the present study was to determine whether fibroblasts isolated from periprosthetic tissues could induce the generation of bone resorbing osteoclasts that would contribute to the osteolysis commonly seen in the periprosthetic loosening. Fibroblast-like cells were isolated from pseudomembrane from patients (n=5) undergoing hip revision due to aseptic loosening, by routine collagenase enzyme digestion. The isolated cells were seeded in flasks for 2–4 weeks before being passaged for a further 3–4 times. Generated fibroblast-like cells (10. 4. ) were then co-cultured with 5x10. 5. normal human peripheral blood monocytes (n=5) on glass coverslips and dentine slices in the presence of (i) no added factors, (ii) macrophage colony stimulating factor (M-CSF) and (iii) M-CSF plus OPG. All cultures were maintained for 1,17 and 21 days. The extent of osteoclast differentiation was then determined by the expression of specific osteoclast markers including tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and evidence of lacunar resorption. In the absence M-CSF, no osteoclast formation was noted in 24 hours, 17 or 21 days in fibroblast/monocyte cultures. However, in the presence of M-CSF alone, large numbers of TRAP. +. and VNR. +. multinucleated cells capable of lacunar resorption were noted in these co-cultures. The addition of OPG, which is known to inhibit RANKL-mediated osteoclast formation, significantly reduced the extent of osteoclast formation and lacunar resorption in these co-cultures. These results indicate that one means whereby peri-prosthetic osteolysis may occur is by fibroblasts in the arthroplasty pseudomembrane inducing macrophage-osteoclast differentiation. Fibroblasts express RANKL and interact with arthroplasty macrophages, which express RANK and function as osteoclast precursors. These findings indicate that suppression of osteoclast formation by OPG may be a possible form of therapy for reducing prosthetic loosening