Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Pharmacoeconomic analysis of biologics and methotrexate for rheumatoid arthritis from the standpoint of the number needed to treat concept under the Japanese health insurance system.

OBJECTIVES: To evaluate the cost-effectiveness of biologics and methotrexate (MTX) for rheumatoid arthritis (RA) using the number needed to treat (NNT) concept and total actual health care cost. METHODS: This study included 121 RA patients with newly prescribed biologics and/or MTX between 2012 and 2017. The NNT was calculated based on the 24 week remission rate of Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI). RESULTS: Remission rates were 76.4% for DAS28-ESR and 45.4% for CDAI in the biologics group and 63.6% and 24.2%, respectively, in the MTX group. The NNT was calculated as 6.4 and 4.2 in the biologics group and 34.2 and 35.2 in the MTX group, respectively. Mean total actual health care costs were 1,044,066 JPY (9835 US$)/24 weeks per treated patient in the biologics group and 75,860 JPY (715 US$)/24 weeks in the MTX group. Although the effectiveness of biologics was superior to MTX from the standpoint of NNT, the mean total health care cost and mean cost per NNT were much higher in the biologics group. CONCLUSIONS: Cost-effectiveness is clearly higher for MTX than biologics from the standpoint of mean total health care cost per adjusted NNT under the Japanese health insurance system.

Risk Factors Associated with Aggravation of Cervical Spine Lesions in Patients with Rheumatoid Arthritis: A Retrospective Longitudinal Cohort Study.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To examine factors related to severe aggravation of preexisting cervical lesions in patients with rheumatoid arthritis (RA) under current pharmacologic treatments with biologics. SUMMARY OF BACKGROUND DATA: Advanced RA cervical lesions carry a risk of irreversible damage to the spinal cord; however, risk factors for aggravation are unclear after the use of biologics became more popular. METHODS: Of 166 patients with preexisting cervical lesions at baseline, 87 who had cervical X-ray images taken at baseline and at the final visit (with an interval of more than 1 yr) were evaluated retrospectively. Aggravated instabilities determined at the final visit, were defined as follows: atlantoaxial subluxation (AAS) = atlantodental interval ≧ 10 mm; vertebral subluxation (VS) = a Ranawat value < 10 mm; and subaxial subluxation (SAS) = an anterior vertebral slip ≧ 4 mm or a multilevel slip ≧ 2 mm. Patients were divided into two groups based on the radiographic results: severe aggravation and non-severe aggravation. Explanatory variables were gender, age of RA onset, duration of disease, average observation period, Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) at baseline, drug treatment history, presence of mutilating deformities in the hands, presence of RA-related joint surgery, and the prevalence of each cervical lesion at baseline. RESULTS: The severe group comprised 14 patients (16.1%). There was no significant difference between the two groups with respect to demographic data. Multivariate logistic regression analysis revealed that preexisting SAS lesions (odds ratio: 7.59, 95% confidence interval: 1.16-49.6) and no history of biologic treatment (odds ratio, 0.10; 95% confidence interval, 0.17-0.58) were associated with aggravation. CONCLUSION: Preexisting SAS lesions were associated with aggravation. Meanwhile, biologics may be effective at preventing aggravation.Level of Evidence: 3.

Risk factors associated with cervical spine lesions in patients with rheumatoid arthritis: an observational study.

BACKGROUND: Few reports have described the association between rheumatoid arthritis (RA) cervical lesions and osteoporosis, especially in patients with vertical subluxation (VS) that could be induced by the collapse of lateral masses in the upper cervical spine. Therefore, this study aimed to investigate the prevalence and risk factors for cervical lesions in patients with RA under current pharmacological treatments with biological agents, and to investigate the relationship between osteoporosis and VS development. METHODS: One hundred eighty-five consecutive patients with RA who underwent both cervical plain radiography and bone mineral density (BMD) scanning were enrolled. RA cervical lesions included atlantoaxial subluxation (AAS), VS, and subaxial subluxation (SAS). We assigned patients with AAS, VS, or SAS to the cervical-lesion group, and all other patients to the non-cervical-lesion group. Radiological findings, BMD, and clinical data on RA were collected. We used multivariate logistic regression analyses to assess the risk factors for cervical lesions in patients with RA. RESULTS: The cervical-lesion and non-cervical-lesion groups included 106 and 79 patients, respectively. There were 79 patients with AAS, 31 with VS, and 41 with SAS. The cervical-lesion group had a younger age of RA onset, longer RA disease duration, higher RA stage, and lower femoral neck BMD than the non-cervical-lesion group. Multivariate analyses showed that the risk factors for RA cervical lesions were prednisolone usage, biological agent usage, and higher RA stage. Prednisolone usage and femoral neck BMD were the risk factors for VS. CONCLUSIONS: Cervical lesions were confirmed in 57 % of the patients. Prednisolone usage, biological agent usage, and higher RA stage were significant risk factors for cervical lesions in patients with RA. The general status of osteoporosis might contribute to the development of VS.

Effects of forefoot arthroplasty on plantar pressure, pain, gait and disability in rheumatoid arthritis.

Objectives: The purpose of this study was to clarify the effect of forefoot arthroplasty on plantar pressure, pain, gait, and disability within 1 year after arthroplasty in patients with RA.Methods: Eleven patients with RA who underwent forefoot arthroplasty completed this quasi-experimental study. Outcome measures were in-shoe plantar pressure, visual analog scale (VAS) for pain, temporal gait parameters, and modified Health Assessment Questionnaire (mHAQ), obtained preoperatively and at 4 and 12 months postoperatively.Results: The average peak plantar pressure under the 2nd metatarsal head decreased at 4 months postoperatively, compared to preoperative values (p < .05) and the decreased plantar pressure was sustained at 12 months postoperatively. Similar changes were observed under the 3rd to 5th metatarsal heads. The median VAS for foot pain decreased from 25 mm preoperatively to 1 mm at 4 months postoperatively and the lower score was sustained at 12 months postoperatively (p < .05). The median mHAQ score remained lower (<1.0) at all measurement points. Regarding gait, there were no significant differences from the preoperative assessment to postoperative follow-up.Conclusion: Plantar pressure and forefoot pain decreased at 4 and 12 months after forefoot arthroplasty in patients with RA. No adverse effects on gait parameters or disability were observed.

Does Abatacept Increase Postoperative Adverse Events in Rheumatoid Arthritis Compared with Conventional Synthetic Disease-modifying Drugs?

OBJECTIVE: To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. RESULTS: A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). CONCLUSION: Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.

Factors associated with disease activity after orthopaedic surgery in patients with rheumatoid arthritis.

Objective: This study evaluated the effect of surgical intervention on disease activity and factors associated with postoperative disease activity in patients with rheumatoid arthritis (RA).Methods: One hundred and seventy-five patients with RA who underwent a single orthopaedic surgical procedure with 1 year of follow-up were retrospectively reviewed to assess postoperative changes in disease activity using disease activity score in 28 Joints calculated with C-reactive protein (DAS28-CRP). European League against Rheumatology (EULAR) response criteria were used to assess the response to surgical intervention.Results: Overall disease activity was significantly improved after surgery. Therapeutic regimens including biological/targeted-synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs), methotrexate (MTX), and prednisolone (PSL) were not significantly changed 1 year after surgery. Shorter disease duration, surgery of large joints, higher baseline DAS28-CRP, and no use of b/tsDMARDs affected postoperative improvement of disease activity. Multivariate logistic regression analysis revealed that large joint surgery and no preoperative use of b/tsDMARDs were independent factors leading to good response to EULAR criteria after surgery (OR = 2.70; 95% CI, 1.03-7.06; p < .05, OR = 4.09; 95% CI, 1.50-11.14; p < .01, respectively).Conclusion: Significant improvement of disease activity after surgical intervention may be expected in patients with RA with large joint surgeries or no preoperative use of b/tsDMARDs.

In Asian women undergoing total knee arthroplasty, lower leg morphology in those with rheumatoid arthritis differed from those with osteoarthritis.

Objectives: This retrospective, single-center study aimed to compare leg morphology between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA) undergoing total knee arthroplasty (TKA).Methods: We enrolled 70 RA and 327 OA female patients undergoing TKA. Hip-knee-ankle angle (HKA), femorotibial angle (FTA), valgus correction angle (VCA), and femoral/tibial bowing were measured using full-length radiographs. Femoral bowing of more than 3° or tibial bowing more than 2°, either laterally or medially, was considered substantial. Distribution of these results and the incidence of substantial bowing in RA and OA were compared.Results: HKA, FTA, and VCA were significantly smaller in RA than those in OA. Femoral bowing was significantly smaller in RA (mean angle: 0.04° ± 3.1°) than that in OA (mean angle: 2.1° ± 3.6°) (p < .05). In almost half of the patients with RA (48.6%), femoral bowing occurred medially, whereas femoral bowing occurred laterally in approximately three quarters of OA patients (73.1%). Tibial bowing did not differ. The incidence of substantial femoral bowing was significantly lower in RA (27.1%) than that in OA (43.0%) (p < .05).Conclusion: RA patients undergoing TKA had different leg morphology than OA patients. These findings have implications for surgical planning.

Clinical and radiographic evaluation of total hip arthroplasties using porous tantalum modular acetabular components: 5-year follow-up of clinical trial.

OBJECTIVES: Porous tantalum is a biomaterial newly applied for artificial joints. We present here 5-years follow-up report of a multicenter clinical trial of total hip arthroplasties (THA) with porous tantalum modular acetabular component (modular PTC). METHODS: Study participants received 82 hips in 79 cases, with 61.2 months follow-up on average. Age at operation was 60.9 years. Clinical results were evaluated using Merle d'Aubigne Postel score. Presence of implant loosening, periacetabular radiolucency, osteolysis, and gap filling were examined for radiographic results. RESULTS: Merle d'Aubigne Postel score improved from 10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year, with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm; however, all showed bone filling within 12 months. PTC with oversized reaming was significantly less likely to have a gap. No implant failure was noted related to modularity. Resulting survival rate of modular PTC was 100% at 5 years. CONCLUSIONS: Modular PTC showed excellent results at 5-years of follow-up. Some hips showed periacetabular gaps, which were filled with bone within 1 year. Further follow-up was needed to determine long-term efficacy.

Mid- term results of stryker® scorpio plus mobile bearing total knee arthroplasty.

BACKGROUND: The mobile bearing knee system was introduced to lessen contact stress on the articular bearing surface and reduce polyethylene wear. The purpose of the current study was to investigate the mid-term results of patients undergoing total knee arthroplasties (TKAs) using Scorpio Plus Mobile Bearing Knee System (Stryker, Mahwah, NJ), and compare the outcomes between patients with osteoarthritis and osteonecrosis (OA·ON group) and patients with rheumatoid arthritis (RA group). METHODS: Eight males and 58 females were followed up for a period of 4.4- 7.6 years from June 1, 2003 to December 31, 2005. There were 53 knees with osteoarthritis, 17 knees with rheumatoid arthritis, and 6 knees with osteonecrosis. Clinical and radiographic follow- up was done using The Japanese Orthopedic Association knee rating score (JOA score) and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. RESULTS: With regard to the JOA score, there was significant improvement in both groups. The postoperative range of motion was between 0.8°and 116.8° in OA·ON group, and between 0.0° and 113.7° in RA group. There were no significant differences with the radiographic evaluation between two groups. Spontaneous dislocation of a polyethylene insert occurred in one patient, and deep infection was occurred in one patient. CONCLUSION: There was significant improvement with regard to the clinical and radiographic results of patients undergoing TKAs using the model. The risk of polyethylene insert dislocation related to the mobile bearing TKA is a cause for concern.

Good long-term outcome of synovectomy in advanced stages of the rheumatoid elbow.

BACKGROUND AND PURPOSE: Synovectomy is an effective procedure for management of the rheumatoid elbow at radiographically early stages (Larsen grades 1 and 2). However, its efficacy for advanced stages (Larsen grades 3-5) is controversial. We investigated the outcome of synovectomy for advanced stages of the rheumatoid elbow. METHODS: Between May 1985 and September 1994, synovectomy was performed for 67 rheumatoid elbows in 59 patients (mean age 52 (26-72) years, 54 women). 3 elbows (3 patients) were lost to follow-up after mean 15 (10-23) years. Thus, 64 elbows were evaluated clinically and radiographically. RESULTS: The mean Mayo elbow performance score (MEPS) improved from 42 (15-75) points preoperatively to 78 (45-100) points at the final follow-up examination. In cases of Larsen grade 5, the mean MEPS at final follow-up examination (69 points) was lower than those of Larsen grade 3 and 4 cases (80 and 79 points, respectively) (p < 0.01). Recurrence of synovitis was obvious in 20/67 elbows. 12 cases had a total elbow arthroplasty mean 13 years after the synovectomy. The 10-year, 15-year, and 20-year survival rates were 97%, 75%, and 70%, respectively. INTERPRETATION: Our findings suggest that synovectomy for the rheumatoid elbow gives a good long-term outcome for radiographically judged destroyed joints of Larsen grades 3-4.

Change in pelvic tilt angle 2 to 4 years after total hip arthroplasty.

The purpose of this study was to evaluate the change in pelvic tilt angle (PA) in the sagittal plane in the standing and supine positions for 2 to 4 years after total hip arthroplasty (THA). Anteroposterior pelvic radiographs of 21 male and 65 female patients were investigated before and after THA yearly over 2 to 4 years. Both the standing and supine PA significantly posteriorly tilted after THA. The difference in PA between the standing and supine positions (dPA) significantly increased after THA. Although the PA in the standing and supine positions plateaued 1 year after THA, the dPA gradually increased. In addition, the percentage of patients who showed a difference of more than 10° in dPA tended to increase yearly. In particular, elderly female patients who showed posterior tilt in PA in the standing or supine positions or a large dPA before THA tended to show a dPA of more than 10° after THA.

Clinical and radiological results of GSB III total elbow arthroplasty in patients with rheumatoid arthritis.

Total elbow arthroplasty (TEA) with the GSB III prosthesis was performed in 32 patients (36 elbows) with rheumatoid arthritis between 2001 and 2009. At final follow-up, 31 patients (35 TEAs) were available for clinical and radiological evaluation. The mean follow-up period was 6.3 (2.0-10.3) years, with a minimum follow-up of 2 years. The mean Mayo elbow performance score was significantly improved from 48 points preoperatively to 83 points at final follow-up. The radiographic loosening rate was 14.3% for humeral components and 5.7% for ulnar components. There were 4 cases of intraoperative fracture and 1 case of humeral shaft fracture at 4 months after surgery. The rates for loosening and fracture were relatively low when compared with those in other studies of linked TEA. There were 2 cases of ulnar nerve palsy, but there was no deep infection or triceps disruption. The clinical results of TEA using the GSB III prosthesis in patients with rheumatoid arthritis were found to be satisfactory.

Risk of postoperative complications in rheumatoid arthritis relevant to treatment with biologic agents: a report from the Committee on Arthritis of the Japanese Orthopaedic Association.

PURPOSE: Since biologic agents were introduced to treat rheumatoid arthritis (RA) in 2003, the number of orthopedic surgical procedures under treatment with biologic agents has been increasing in Japan. However, whether biologic agents cause an increase in the prevalence of postoperative complications is as yet unknown. The Committee on Arthritis of the Japanese Orthopedic Association investigated the prevalence of postoperative complications in patients with RA in teaching hospitals in Japan. METHODS: Between January 2004 and November 2008, surveillance forms about medications and surgical procedures in patients with RA were sent to 2,019 teaching hospitals. Data were analyzed by the Rheumatoid Arthritis Committee. RESULTS: Biologic agents were administered to RA patients in 632 of 1,245 hospitals (50.8%); 430 of the 1,245 hospitals (34.5%) used surgical intervention under treatment with biologic agents. The number of surgical procedures under treatment with biologic agents was 3,468, and the prevalence of infection was 1.3% (46 cases). The prevalence of infection was 1.0% (567 procedures) in 56,339 procedures under treatment with nonbiologic disease-modifying anti-rheumatic drugs. There were no significant differences between biological and nonbiological treatment groups with respect to the prevalence of infection. In the joint arthroplasty group, the number of procedures under biological and nonbiological treatment was 1,626 and 29,903, and the prevalence of infection was 2.1% (34 procedures) and 1.0% (298 procedures), respectively. There was a significant difference between groups. The odds ratio was 2.12 (95% confidence interval 1.48-3.03, P < 0.0001). CONCLUSION: The chance of having biological treatment with joint arthroplasty was more than twofold greater in patients with surgical-site infections compared with those treated with nonbiologic agents. Caution is required for surgical procedure, perioperative course, and obtaining consent for joint arthroplasty for patients with RA undergoing surgery under biological agents.

Dystrophic calcinosis in a patient with rheumatoid arthritis.

We report a rare case of dystrophic calcinosis in a patient with rheumatoid arthritis in bilateral buttock lesions and the right elbow joint. The calcinosis was surgically removed because it caused severe local pain, possible infection, and difficulty in sitting. Because no recommended standard pharmacotherapy exists for dystrophic calcinosis, surgical treatment should be taken into consideration when calcinosis causes severe local pain or restricts activities of daily life.

Clinical and radiological results of non-cement impaction bone-graft method of total hip arthroplasty for rheumatoid arthritis.

We performed total hip arthroplasty using the non-cement impaction auto-bone-grafting method with the resected femoral head for acetabular protrusion that is not combined with the destruction of acetabular rim or dysplasia of the hip joint. Ten patients (eight women and two men) with rheumatoid arthritis who showed acetabular protrusion underwent total hip arthroplasty using this method. All patients were able to walk with full weight within 5 days after surgery. The short-term results of our cases were very good. The postoperative periods of the radiographic-bone incorporation of the grafting bone were 2 months after surgery in four joints, 3 months after surgery in four joints, and 4 months after surgery in three joints. There were no cases that showed any migration or radiolucency around the acetabular component at the time of follow-up. Our operative technique is simple and easy, and it is a useful method for the treatment of protrusion in patients with rheumatoid arthritis.

Primary cervical epidural malignant lymphoma with rheumatoid arthritis: a case report.

We report a case of primary cervical epidural malignant lymphoma with rheumatoid arthritis. Because of the acute progression of paralysis in both legs, surgical decompression and stabilization of the cervical spine were performed. The resected specimen showed proliferation of lymphoblastic cells diagnosed as malignant lymphoma. Four series of chemotherapy were administered after surgery, and the patient recovered from paralysis.

Alendronate does not inhibit early bone apposition to hydroxyapatite-coated total joint implants: a preliminary study.

BACKGROUND: Alendronate is a pyrophosphate analogue of bisphosphonate that has been shown to inhibit osteoclastic bone resorption. Bone formation and remodeling are necessary to establish initial fixation of uncemented implants, especially those coated with a bioactive surface such as hydroxyapatite. Because the process of bone-remodeling that culminates in new-bone formation is thought to be initiated by osteoclastic bone resorption, it is appropriate to test the influence of osteoclast-inhibiting medications on bone apposition to hydroxyapatite-coated implants. METHODS: Twelve dogs underwent staged bilateral total hip arthroplasty, with twenty weeks between the first and second operations, with use of a titanium-alloy femoral stem that had a proximal macrotextured surface and a plasma-sprayed hydroxyapatite coating. Six of the dogs received oral alendronate therapy from the time of the surgery until they were killed; the other six dogs were untreated controls. The animals were killed four weeks after the second operation. Sections from matched implant sites (proximal, middle, and distal) were histologically analyzed. The linear extent of bone apposition, the linear extent and the thickness of the hydroxyapatite coating, and the total amount of cortical and trabecular bone were measured with the use of an interactive image analysis system. RESULTS: There were no significant differences in radiographic or histologic findings between the two groups at either four or twenty-four weeks. Although the extent of the hydroxyapatite coating decreased significantly with time in both groups (p < 0.01), we identified no significant influence of alendronate on the extent of bone apposition, the extent or thickness of the hydroxyapatite coating, or the cortical or trabecular bone area around the implants. CONCLUSIONS: Many patients who are receiving alendronate for osteoporosis or other disorders may also be candidates for cementless total joint arthroplasty. Although bone formation is generally thought to be initiated by and coupled with bone resorption, our results suggest that alendronate has no discernible effect on the initial fixation of or the short-term bone-remodeling around hydroxyapatite-coated femoral total joint implants.

The effect of particle wear debris on NFkappaB activation and pro-inflammatory cytokine release in differentiated THP-1 cells.

Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. Previous in vitro studies have reported that particles of wear debris induce the release of pro-inflammatory cytokines and other inflammatory mediators from macrophages and other cells. Several recent investigations, however, have suggested that the wear particles themselves may not be primarily responsible for the inflammatory cellular responses, but that the observed cytokine release in vitro may be caused by endotoxin adsorbed to commercially available particle preparations. The intracellular pathways involved in macrophage signal transduction also are poorly understood. The purposes of this study are to use isolated orthopedic wear debris particles to evaluate pro-inflammatory cytokine release and nuclear factor kappa B (NFkappaB) activation from macrophages. Cells from human monocyte/macrophage cell line (THP-1) were differentiated and incubated with particles of debris that had been isolated from a failed human total hip arthroplasty. The titanium-alloy particles did not evoke release of TNF-alpha or IL-1beta whereas lipopolysaccharide (LPS) or LPS-treated debris particles induced both TNF-alpha and IL-1beta. LPS-treated particles, but not particles alone, stimulated NFkappaB activation. Our results suggest that at the concentrations tested in this study, endotoxin-free wear debris particles may not themselves initiate inflammatory cellular responses in differentiated THP-1 cells. It is unclear whether adsorbed endotoxin is clinically associated with osteolysis and/or loosening in total joint arthroplasties, but several factors, including adsorbed endotoxin, need to be investigated to explore the cellular responses responsible for osteolysis and/or loosening.

Histologic and quantitative wear particle analyses of tissue around cementless ceramic total knee prostheses.

We histologically analyzed tissue biopsy specimens obtained from 4 cases of revised cementless ceramic knee prostheses. Particles were isolated from the specimens, and their size and composition were determined. Implants were removed for aseptic loosening at an average of 64 months. Histologically, polyethylene particles were seen in all cases. The concentration of the particles showed wide variation among cases. The concentration of the particles also showed a wide variation among different biopsy locations, suggesting that the particles were not distributed uniformly around the knee prostheses. Although we analyzed only 4 cases, our results show good correlation between radiographic evidence of geographic osteolysis and the concentration of wear particles. Multiple biopsy specimens may be necessary to characterize adequately particle migration around knee prostheses.