Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Decennial trends in hip fractures over 20 years in Yamagata Prefecture, Japan.

BACKGROUND: Hip fracture is among the most common injuries in elderly people. We aimed to investigate the decennial trends in hip fractures in patients ≥65 years of age. METHODS: A questionnaire was distributed to all hospitals with a Department of Orthopaedic Surgery in Yamagata Prefecture to collect data on hip fractures occurring in 1996, 2006 and 2016. RESULTS: The response rate was 100%. The total numbers of hip fractures in 1996, 2006 and 2016 were 665, 1169 and 1,728, respectively (crude incidence: 258, 373 and 494 per 100,000 person-year, respectively). Injuries frequently occurred in the early morning and daytime morning in 1996. In contrast, they frequently occurred in activity times (e.g., morning and afternoon) in 2006 and 2016. Among the patients, 80-90% were injured by simple falls, and 70-80% were injured indoors. The incidence of trochanteric fractures was approximately 1.8-1.9 times greater than incidence of neck fractures in all years. Especially, trochanteric fractures in females of ≥90 years of age markedly increased. The rate of surgical treatment was the same in 1996 and 2006, but was lower in 2016. In 1996, the percentage of independent walkers at discharge and 1 year later was almost the same. In 2006 and 2016, the rate of independent walkers was low at discharge, but increased 1 year later. The rate of discharge to home decreased gradually. The combined percentage of patients discharged to home and to rehabilitation institutions in 2006 and the percentage of patients who entered the regional referral clinical pathway in 2016 were both approximately 70%, with no marked changes observed. CONCLUSIONS: Hip fractures, especially trochanteric fractures in super-aged females, increased. Discharge to home decreased, and the use of the regional referral clinical pathway was widespread. Ambulation ability was reduced at discharge, but improved after 1 year.

Differences in subtrochanteric and diaphyseal atypical femoral fractures in a super-aging prefectural area: YamaCAFe Study.

INTRODUCTION: Atypical femoral fractures (AFFs) have been correlated with long-term use of bisphosphonates (BPs), glucocorticoids (GCs), and femoral geometry. We investigated the incidence and characteristics of subtrochanteric (ST) and diaphyseal (DP) AFFs in all institutes in a super-aging prefectural area. MATERIALS AND METHODS: We performed a blinded analysis of radiographic data in 87 patients with 98 AFFs in all institutes in Yamagata prefectural area from 2009 to 2014. Among the 98 AFFs, 57 AFFs comprising 11 ST fractures in 9 patients and 46 DP fractures in 41 patients with adequate medical records and X-rays were surveyed for time to bone healing and geometry. RESULTS: Of the 87 patients, 67 received BPs/denosumab (77%) and 10 received GCs (11%). Surgery was performed in 94 AFFs. Among 4 AFFs with conservative therapy, 3 required additional surgery. In univariate regression analyses for ST group versus DP group, male-to-female ratio was 2/7 versus 1/40, mean age at fracture was 58.2 (37-75) versus 78 (60-89) years, rheumatic diseases affected 55.5% (5/9) versus 4.9% (2/41), femoral lateral bowing angle was 1.7 (0-6) versus 11.8 (0.8-24)°, GC usage was 67% (6/9) versus 4.9% (2/41), and bone healing time was 12.1 (6-20) versus 8.1 (3-38) months (p < 0.05). In multivariate analyses, higher male-to-female ratio, younger age, greater proportion affected by rheumatic diseases, and higher GC usage remained significant (p < 0.05). CONCLUSIONS: The incidence of AFFs in our prefectural area was 1.43 cases/100,000 persons/year. This study suggests that the onset of ST AFFs have greater correlation with the worse bone quality, vice versa, the onset of DP AFFs correlated with the bone geometry. The developmental mechanisms of AFFs may differ significantly between ST and DP fractures.

Disassembly of bilateral bipolar heads within 10 years after hip hemiarthroplasties for avascular necrosis of femoral heads: a case report.

Prosthetic joint surgeries, total hip arthroplasty (THA) or bipolar hemiarthroplasty (BHA) and joint preservation surgeries can be performed for avascular osteonecrosis of femoral head (ONFH) with collapse. Although excellent surgical results have been reported, long-term survivorship and postoperative complications are a great concern. The purpose of this study was to report a case of bilateral disassembly of bipolar heads within 10 years after BHA for ONFH. A 61-year-old man, whose occupation was carpenter, underwent bilateral BHA for ONFH at another hospital when he was 57 years old. He had acute right hip pain during working and visited our institute. Radiographs revealed intra-articular (outer and inner head) disassembly of the right bipolar head, and conversion to THA was performed. Five years later, he had contralateral (left) hip pain. Radiographs revealed disassembly of bipolar head, as had occurred with the right hip, and similar conversion surgery was performed for the left hip. Marked wear and detachment of the polyethylene bearings of the outer head and failure of the locking mechanism between a skirted 22-mm-diameter inner head and polyethylene insert were observed in both hips at each revision surgery. Degeneration of the acetabulum were also observed in both hips. The failure of the self-centering mechanism because of degenerative change of the acetabulum, impingement of the outer head and neck, and high activity seemed to be the causes of disassembly of the bilateral bipolar heads. Therefore, it is important to select the type of prostheses depending on the age, activity and occupation of each patient.

Rapid disappearance of gouty tophi of the foot by resection of massive gouty tophi of the opposite foot in a patient with hyperuricaemia: a case report.

Gouty tophi occur less frequently and disappear only with modern medication therapy for symptomatic or asymptomatic hyperuricaemia. However, the medication may require a long time to take effect due to the systemic urate pool associated with massive gouty tophi. We present the case of a 37-year-old woman who suffered from massive gouty tophi of both feet due to hyperuricaemia. After resection of the massive gouty tophi from her right foot and treatment with uricemia medication, the gouty tophi of her opposite foot disappeared rapidly due to reducing the patient's systemic urate pool with intensification of drug medication.

Quality of life of patients with osteonecrosis of the femoral head: a multicentre study.

PURPOSE: Quality-of-life (QOL) assessments in patients with osteonecrosis of the femoral head (ONFH) have rarely been reported. This multicentre study aimed to elucidate the relationship between disease severity, including necrotic lesion type and radiological staging, and QOL, as well as between patients' characteristics and QOL. METHODS: Two hundred seventy-four patients with ONFH (108 females, 166 males; median age, 46 years) were asked to complete self-assessment QOL questionnaires including the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire, Oxford Hip Score, and SF-12v2. RESULTS: Patients with large necrotic lesion type or collapsed ONFH had low QOL scores. Among patients with non-collapsed lesions, patients with alcohol-associated ONFH had lower QOL scores than those with steroid-associated ONFH, those with bilateral ONFH had lower mental scores, and male patients had worse social condition scores. Among patients with collapsed lesions, middle-aged patients exhibited lower mental QOL, and a strong correlation was observed between social activity and mental health. CONCLUSION: Collapsed ONFH was associated with low QOL scores. Among patients with non-collapsed lesions, alcohol-associated ONFH, bilateral disease, and male sex were linked to low QOL scores.

The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes.

Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased the messenger RNA (mRNA) levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1ß, whereas reinforced secretion of IL-1ß was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1ß release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions.

Prevention of excessive postoperative sliding of the short femoral nail in femoral trochanteric fractures.

INTRODUCTION: Lag screw cut-out is one of the major postoperative complications on femoral trochanteric fractures. However, precise analyses of excessive sliding and lag screw cut-out were limited. The purpose of this study was to investigate the factors that induce this unfavorable event. METHODS: From April 2010 to April 2013, 226 patients were operated in our institute using a short femoral nail. Among them, 177 patients (29 males and 148 females) with a mean age of 84 years (60-97 years), who were followed up >3 months, were included in this study. The postoperative sliding distance, fracture type (AO/OTA classification), tip-apex distance (TAD), reduction pattern in the postoperative X-ray (antero-posterior and lateral views), bone quality (canal flare and cortical indices), walking ability at the time of pre-injury and final follow-up, and complications were investigated retrospectively. RESULTS: The mean sliding distance was 3.7 mm, and one cut-out case (0.6 %) was observed. The sliding distance of the AO/OTA 31-A2 fractures was significantly longer than that of the A1 fractures (p < 0.0001). Regarding the reduction pattern, the sliding distance of the intramedullary type was longer than that of the extramedullary and anatomical types in the lateral view (p < 0.01, p < 0.001, respectively). Further, even in the medial and anatomical types, where the reduction patterns are recommended in the antero-posterior view, the sliding distance of the intramedullary type was significantly longer than that of the anatomical type in the lateral view. There was no correlation of bone quality with the sliding distance. CONCLUSIONS: Because the sliding distance increased in the intramedullary type in the lateral view of unstable fractures, an accurate reduction in the lateral view at surgery is important, particularly in unstable fractures.

Inflammatory immune cell responses and Toll-like receptor expression in synovial tissues in rheumatoid arthritis patients treated with biologics or DMARDs.

Biologic antirheumatic drugs (BIO) have been reported to be potent therapeutic agents in the prevention of inflammatory joint destruction in rheumatoid arthritis (RA). The aim of this study was to investigate the immune-inflammatory cells, including Toll-like receptor (TLR)-equipped cells, in synovial tissue samples from RA patients on BIO compared to patients, who are only on conventional disease-modifying antirheumatic drug (DMARD). We analyzed immune-inflammatory cells in RA synovitis in patients of BIO group (n = 20) or DMARD group (n = 20). The grading scores of synovitis was 1.7 and 1.8 in each BIO and DMARD group and correlated best with the CD3(+) T (r = 0.71/0.70, p < 0.05) and CD20(+) B (r = 0.80/0.84, p < 0.05) cells in the both groups, but less well with the CD68(+) macrophages and S-100(+) dendritic cells (DCs). Interestingly, both T (116 vs. 242, p < 0.05) and B (80 vs. 142, p < 0.05) cell counts were lower in the BIO than in the DMARD group, whereas macrophage and DC counts did not differ. In contrast, the C-reactive protein (CRP) and disease activity score DAS28-CRP did not show clear-cut correlations with the inflammatory grade of the synovitis (r range, 0-0.35). Similar numbers of cells immunoreactive for TLR-1 to TLR-6 and TLR-9 were found in synovitis in both groups. Patients clinically responding to biologics might still have the potential of moderate/severe local joint inflammation, composed in particular of and possibly driven by the autoinflammatory TLR(+) cells.

Minocycline-induced periarticular black bones in inflamed joints which underwent arthroplastic reconstruction.

BACKGROUND: Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone. METHODS: We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries. RESULTS: All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination. CONCLUSIONS: No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periarticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.

Postoperative prophylactic effect of fondaparinux for prevention of deep venous thrombosis after cemented total hip replacement: a comparative study.

The aim of this study was to estimate the effective administration procedure of fondaparinux for prevention of venous thromboembolism after cemented total hip replacement (THR) in Japanese patients. The study included 471 Japanese patients. The dose regimens were 2.5 mg daily for 14 days (2.5 mg/14 day group) or 10 days (2.5 mg/10 day group), 1.5 mg daily for 10 days (1.5 mg group), 2.5 mg daily for the first 3 postoperative days and 1.5 mg daily for the subsequent 7 days (Mixed group), and no administration of fondaparinux (Control group). Deep venous thrombosis (DVT) was diagnosed by ultrasonography on postoperative day 3 or 4 and day 14. The 2.5 mg/14 day, 2.5 mg/10 day and Mixed groups were regarded as one group in the assessment on postoperative day 3 or 4, and denoted as the 2.5 mg group. The incidence of DVT on postoperative day 3 or 4 in the 2.5 mg group was significantly lower than that in the Control and 1.5 mg groups. On postoperative day 14, the incidence of DVT in the 1.5 mg and Mixed groups was significantly lower than that in the Control group in both the intention-to-treat and per-protocol analyses. The incidence in the 2.5 mg/10 day and 2.5 mg/14 day groups was significantly lower than that in the Control group in only the per-protocol analysis. The results suggest that the administration protocol of the Mixed group is effective in preventing DVT in Japanese patients undergoing cemented THR.

Toll-like receptors and their adaptors are regulated in macrophages after phagocytosis of lipopolysaccharide-coated titanium particles.

Macrophages phagocytose metallic wear particles and produce mediators, which can induce cellular host response and aseptic implant loosening. Lipopolysaccharide (LPS) on the wear debris can stimulate macrophages via Toll-like receptor 4 (TLR4) and enhance the response. However, the precise functional role and interaction of TLRs and their adaptor molecules is still unclear. Rat bone marrow macrophages were stimulated with titanium particle (Ti) coated by LPS (Ti/LPS+) and LPS-free Ti (Ti/LPS-). mRNA levels of cytokines, TLRs and their adaptor molecules were measured using real time PCR. mRNA levels of TNF-α, IL-1ß, and IL-6 increased in Ti/LPS+ than Ti/LPS-. In contrast, mRNA levels of TLR4, TLR5, and TLR9 decreased in Ti/LPS+ compared to Ti/LPS-. mRNA levels of MyD88, IRAK1, IRAK4 decreased gradually, and TRAF6 underwent an initial transient increase, followed by suppression in Ti/LPS+. However, mRNA levels of TLR2 and IRAK2 increased after phagocytosis of Ti/LPS+ than Ti/LPS-. The increased expressions of proinflammatory cytokines found in Ti/LPS+ indicated that their productions cytokines could be enhanced by phagocytosis of LPS-coated particles. Subsequent down-regulation of TLR4, TLR5, TLR9, MyD88, IRAK1, and IRAK4 suggests that self-protective mechanisms to regulate excessive host responses are activated in macrophages. Increase of TLR2 and IRAK2 and a transient increase of TRAF6 in Ti/LPS+ suggest that another possible pathway to modulate TLR-mediated cellular response to prolong inflammatory response in foreign body reaction of aseptic loosening. This down- and/or up-regulation of the potential TLR-mediated responses to LPS-coated particles reflects the proactive behavior of effector cells.

Initial evaluation on subsidence of cemented collarless polished tapered stem applied to the patients with narrow femoral medullar canal.

PURPOSE: The geometry of the proximal femur is one of the important factors for choosing the suitable stem. We have been applied cemented collarless polished tapered (CPT) stem to the patients with small femur. Radiographic evaluation was performed to access the clinical feature of the stem in early stage of the follow-up. METHODS: One hundred total hip arthroplasties with CPT system were performed between October 2004 to February 2006. This study focused on the 53 cases to whom size 1 or smaller sized stem were implanted, and its post-operative period was 41 months (30-46 months). Morphologic classification of preoperative proximal femur, stem alignment, thickness of the cement mantle, cementing technique, subsidence of the stem, improvement in the bone-cement interface, and stress shielding were assessed. RESULTS: The size of the inserted stem was X-SMALL in one case, SMALL in two cases, SIZE 0 in 12 cases, and SIZE 1 in 38 cases. Canal shape of proximal femur was stovepipe type in five cases, normal type in 43 cases, and champagne-flute type in five cases. There was no subsidence in eight cases. 44 stems subsided within 1 mm, one stem subsided 1 to 2 mm, and no stem subsided over 2 mm. In 39 of 45 cases, subsidence was appeared within six months after operation. Marked progressive and excessive subsidence was not seen after the two years of follow-up. CONCLUSIONS: Short term radiographic results of THA with CPT stem to small femur were satisfactory with less unfavorable radiographic findings, which imply contribution to longer survivorship of the stem.

Antibiotics-impregnated cement spacers in the first step of two-stage revision for infected totally replaced hip joints: report of ten trial cases.

BACKGROUND: Periprosthetic infection is one of the serious complications after total hip arthroplasty (THA). This study analyzed the perioperative and postoperative status of patients who underwent antibiotics-impregnated cement spacer technique in the first step of the two-stage revision. METHODS: Ten joints of the nine patients (mean age, 65 years; seven women, two men) received two-stage revision as a result of infection that appeared after primary THAs in seven joints, aseptic revision in one, and recurrent type in two. An antibiotics-impregnated cement spacer made by a mold system was applied in the femoral side of all joints. An acetabular spacer was made by hand using a cup gauge in eight joints with extensive tissue loss. RESULTS: The change of leg length after the first stage was -2.2 mm, and range of hip flexion was 72 degrees on average, respectively. Patients could walk with crutches after the first stage, except one patient with simultaneous infections of both hips and one with fracture of the cement spacer. One fracture of femoral cement spacer, and one dislocation of femoral spacer accompanied by fracture of acetabular cement spacer and curable recurrent infection, were found. In all cases of the second-stage procedure, the acetabular side was reconstructed with allogeneic bone graft with cross plate and that of the femur was by impaction bone grafting method. In the latest follow-up, reconstructed implants were stable. Seven patients could walk without any supportive devices and two could walk with the support of a T-cane. CONCLUSIONS: An antibiotics-impregnated cement spacer in the first step of the two-stage revision was effective not only to compensate tissue loss after removal of the implants and to minimize discrepancy of leg length, but also to contribute to improvement of perioperative and postoperative daily activities of the patient's life as well as treatment of the infection.

Cement removal and bone bed preparation of the femoral medullary canal assisted by flexible endoscope in total hip revision arthroplasty.

PURPOSE: The flexible endoscope was applied to cemented femoral medullary canal to obtain better visual field and assist surgical procedures in total hip revision arthroplasty. METHODS: Fifteen cases of failed cemented total hip joints were analyzed. Efficacy of cement removal was assessed, combined with degree of implant loosening and bone defect, postoperative radiographic findings, and perioperative status of the patients and complications. Status of the bone bed between bone and cement and that of bone grafting were also evaluated. RESULTS: The cement mantle was efficiently extractable in all cases under good exposure and with maintenance of efficient working space. Endoscopic time for cement removal was dependent on the status of the cement-bone interface and bone defect. Rigid and less loosened interfaces, as well as cases of minimal bone defect, required a longer time. However, it was effective to confirm the status of the bone bed during the procedure. Occult foreign-body reaction was detectable in three cases of unloosened interface under endoscopic inspection. Impaction bone grafting was performed in eight cases. The scope was also helpful to confirm the status of a grafted bone bed. Three fractures occurred, of which two cases revealed minor cement leakage and one required additional osteosynthesis with extensive approach. JOA Hip Score was improved, and the implants were stable at latest follow-up. Dislocation was found in two cases. Neither thromboembolic events nor infection was found. CONCLUSIONS: Cement removal in the femoral medullar canal was effectively performed not only in the cases of loose interface but also those of rigid and less-loosened interface under flexible endoscopic inspection. The scope could support cement removal in femoral revisions under good exposure and maintenance of working space, as well as confirmation of bone bed state. Although one case required an additional approach, application of the flexible endoscope has potential merit to contribute to less invasive total hip revision arthroplasty, possibly combined with other refined devices of cement extraction.

Increased expression of toll-like receptors in aseptic loose periprosthetic tissues and septic synovial membranes around total hip implants.

OBJECTIVE: Toll-like receptors (TLR) are transmembrane proteins found in various cells. They recognize infectious and endogenous threats, so-called danger signals, that evoke inflammation and assist adaptive immune reactions. It has been suggested that TLR play a role in periprosthetic tissues and arthritic synovium. Our objective was to elucidate tissue localization and functional roles of TLR in periprosthetic tissues in 2 different pathologic conditions, aseptic and septic implant loosening. METHODS: For immunohistochemistry studies, aseptic synovial-like membranes of periprosthetic connective tissues (n = 15) and septic synovial capsular tissues (n = 5) were obtained at revision surgery and from salvage of infected totally replaced hips, respectively. Osteoarthritic synovial tissues were used for comparison (n = 5). Samples were processed for immunohistopathologic analyses for tissue colocalization of TLR with CD68 and/or CD15 using the Alexa fluorescent system. Total RNA was isolated from frozen tissues and converted into cDNA, TLR 2, 4, 5 and 9 sequences were amplified, and the products were quantified using real-time polymerase chain reaction. RESULTS: Immunofluorescent staining showed colocalization of TLR 2, 4, 5, and 9 with CD68 in the focal monocyte/macrophage aggregates in aseptic synovial-like membranes from loose total hip replacements. TLR 2, 4, 5, and 9 were also found colocalized with CD15+ polymorphonuclear leukocytes and CD68+ mononuclear cells of the synovial membranes from septic total hip replacements. In osteoarthritic synovial tissues, expression of TLR was found only in vascular cells and mononuclear cells, and the reactivity was weak. mRNA levels of TLR 2, 4, 5, and 9 were increased in both aseptic and septic periprosthetic tissues. TLR 2 and 5 were significantly higher than TLR 4 and 9 in aseptic and septic samples. CONCLUSION: Peri-implant tissues were well equipped with TLR in both aseptic and septic conditions. TLR 2- and TLR 5-mediated responses seemed to dominate. In aseptic loosening, monocytes/ macrophages were the main TLR-equipped cells apparently responsible for alarmin-induced responses. This could lead to production of inflammatory cytokines and extracellular matrix-degrading proteinases after phagocytosis of wear debris derived from an implant, but in septic cases they eventually respond to microbial components. Thus, inflammatory cells in both aseptic and septic tissues were equipped with TLR, providing them with responsiveness to both endogenous and exogenous TLR ligands.

Enhanced osteolytic potential of monocytes/macrophages derived from bone marrow after particle stimulation.

BACKGROUND: Total hip replacement can be complicated by periprosthetic osteolysis. Monocytes/macrophages play a major role in the formation of the foreign body granulomas induced by wear debris. We hypothesized that periprosthetic monocytes/macrophages do not only accelerate inflammatory and osteoclast-mediated osteolytic processes, but also resorb periprosthetic bone directly by themselves. This study was designed to evaluate the osteolytic potential in vitro of monocytes/macrophages derived from bone marrow. METHODS: Monocytes/macrophages were produced by filtration of rat bone marrow cells, followed by culture in the presence of macrophage-colony stimulating factor (M-CSF). Monocyte/macrophage properties were ascertained using immunocytochemistry and phagocytic activity. Osteolytic cytokines and extracellular matrix degrading proteinases were quantified at the mRNA level. RESULTS: Adherent cell fraction was immunoreactive for the monocyte/macrophage specific marker CD68 and active in the phagocytosis of carbon particles up to 72 h. They also showed immunoreactivity to cathepsin K, IL-1beta, IL-6, and M-CSF, but mostly did not react to TRAP. mRNA levels of osteolytic cytokines and extracellular matrix degrading proteinases were enhanced, but that of RANKL were not. Monocytes/macrophages resorbed dentine discs and carbonated calcium phosphate was very actively resorbed after stimulation with titanium particles. DISCUSSION: Harvested bone marrow cells expressed monocyte/macrophage phenotype, but not osteoclastic markers. The capacity of these cathepsin-K-positive phagocytic cells to resorb dentine discs and carbonated calcium phosphate in vitro suggests a direct role of monocytes/macrophages in bone resorption and periprosthetic osteolysis. The finding supports our hypothesis and previous histomorphometric observations on the presence of such osteolytic macrophages in vivo around loosening prosthesis.

Upregulation of matrix metalloproteinase (MMP)-1 and its activator MMP-3 of human osteoblast by uniaxial cyclic stimulation.

Proper mechanical loading is essential for bone remodeling and maintenance of human skeletal system. Matrix metalloproteinases (MMPs) are secreted by mesenchymal stromal lining cells and osteoblasts to prepare the initiation sites for osteoclastic bone resorption at the beginning of the remodeling cycle. However, only a few studies have addressed the effect of mechanical stress on MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) in osteoblasts. In this study, the response of human osteoblasts to uniaxial cyclic stretching was investigated to clarify this more in detail. Stretching affected the orientation of the osteoblasts, and quantitative reverse transcription-polymerase chain reaction revealed coordinated upregulation of MMP-1 and its activator MMP-3 mRNA by cyclic 5% stretching at 3 h (p < 0.01). Upregulation of cyclooxygenase-2 mRNA was also found in response to cyclic 1 and 5% stretchings at 1, 3, and 6 h (p < 0.01). No changes were found in MMP-2, TIMP-1, and -2. The mRNA expression of MMP-9 was low and MMP-13 was not detected. This study suggests that MMP-1 and -3, enhanced by uniaxial cyclic mechanical stimulation of osteoblasts, are candidate key enzymes in the processing of collagen on bone surface, which might be necessary to allow osteoclastic recruitment leading to bone resorption. The strain might also play a role in cleaning of demineralized bone surface during the reversal phase, before bone formation starts.