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To decrease hip abductor dysfunction after periacetabular osteotomy using a lateral/trochanteric approach, we aimed to modify transposition osteotomy of the acetabulum (TOA) to not cut the greater trochanter and abductor–iliac crest detachment. We subsequently compared abductor muscle strength recovery between TOAs with [conventional TOA (C-TOA)] and without [modified TOA (M-TOA)] trochanteric osteotomy. C-TOA and M-TOA were performed in 27 and 34 hips, respectively. Hip abduction, flexion and knee extension muscle strength were measured preoperatively and at 3, 5, 10, 24 and 52 weeks postoperatively. The muscle strength ratio of the affected and contralateral lower limbs was compared between the C-TOA and M-TOA groups. Neither the mean Merle d’Aubigné–Postel score at the final follow-up nor the postoperative center-edge angle showed significant differences between the M-TOA and C-TOA groups (15.7 versus 16.4 points; P = 0.25 and 38.5° versus P = 0.62 and 39.8°, respectively). The mean muscle strength ratios of hip abduction at 5, 12 and 24 weeks postoperatively were significantly higher in the M-TOA group than in the C-TOA group (0.62 versus 0.39, 0.76 versus 0.59 and 0.94 versus 0.70; P = 0.03, 0.04 and 0.01, respectively). There were no significant differences between groups at Postoperative Week 52 (P = 0.36). Discomfort at the greater trochanter was observed in 18 hips (66.7%) in the C-TOA group but only in 4 hips (11.2%) in the M-TOA group. In conclusion, M-TOA is less invasive than C-TOA and allows an earlier recovery of abductor muscle strength without significant correction loss.

Background To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient’s satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients. Methods This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient’s satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment. Results This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, “very satisfied” and “satisfied” were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50–64 years; OR 0.91; 65–74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas. Conclusions In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

We examined osteoporosis medication use and factors affecting persistence in 497 patients with fragility hip fractures. Only 25.5% of patients received continuous medication for 3 years, and 44.1% of patients received no treatment. Low Barthel index at discharge was a risk factor for both non-treatment and non-persistence to osteoporosis medication. Fragility hip fractures (FHF) caused by osteoporosis decrease the quality of life and worsen life expectancy. Use of osteoporosis medication may be an efficient method in the prevention of secondary FHF. However, previous studies have reported low rates of osteoporosis medication and persistence after FHF. This study aimed to evaluate osteoporosis medication use and factors affecting persistence in patients with FHF in the northern Kyushu area of Japan. A total of 497 FHF patients aged ≥ 60 years with a 3-year follow-up were included. We prospectively collected data from questionnaires sent every 6 months regarding compliance with osteoporosis medication. We compared baseline characteristics among three groups: no treatment (NT), no persistence (NP), and persistence (P), and conducted multivariable regression models to determine covariates associated with non-treatment (NT vs. NP/P) and non-persistence (NP vs. P). There were 219 (44.1%), 151 (30.4%), and 127 (25.5%) patients in the NT, NP, and P groups, respectively. Factors associated with non-treatment were male sex, chronic kidney disease, no previous osteoporosis treatment, and low Barthel index (BI) at discharge. The only factor associated with non-persistence was a low BI at discharge. Factors associated with a low BI at discharge were male sex, older age, trochanteric fracture, and surgical delay. Low BI at discharge is a risk factor for both non-treatment and non-persistence to osteoporosis medication. Therefore, appropriate interventions to improve BI may result in persistence to osteoporosis medication.

We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO.

Dislocation is a leading cause of failure after revision total hip arthroplasty (THA). This study was conducted to examine the risk factors for dislocation as well as their recurrence after revision THA. We retrospectively reviewed 178 revision THAs in 162 patients between 1998 and 2013. The mean patient age was 65.2 years at operation and the mean follow-up period was 6.7 years. Multivariate logistic regression was performed to identify risk factors for dislocation, and further comparison was made between patients with single and recurrent dislocations. Sixteen hips in 15 patients (9.0 %) dislocated at a mean of 9.1 months (range, 0–83 months) after revision THA. Multivariate analysis identified advanced age (odds ratio [OR] = 2.94/10 years) and osteonecrosis of the femoral head (OR = 7.71) as the independent risk factors for any dislocations. Risk factors for recurrent dislocations, which were observed in eight hips (50 %), were later dislocations (≥4 months) and lower BMI. Dislocation is a serious problem after revision THA with multiple risk factors. Although our findings were limited to revision THAs done through posterolateral approach, recognition of these factors is helpful in patient education and surgical planning.

This study was conducted to evaluate the period from symptom onset to diagnosis of ankylosing spondylitis (AS) in Japanese patients and to examine possible reasons for delayed diagnosis.Seventy-two consecutive patients with AS were studied. Diagnostic delay was defined as the gap between the first spondyloarthropathic symptom and diagnosis of AS according to the modified New York criteria.The mean patient ages at disease onset and diagnosis were 25.6 ± 11.3 and 33.3 ± 13.2 years old, respectively, resulting in diagnostic delay of 6.7 years. The number of medical institutions to which patients were referred before diagnosis was 2.4, and orthopedic surgeons were most commonly visited (62%). Non-specific low back pain or lumbar spondylitis (33%) and degenerative arthritis (28%) were the primary diagnoses preceding that of AS. Absence of articular symptoms significantly correlated with diagnostic delay. The patients with disease onset on year 2000 or later had significantly shorter periods until diagnosis than those before 2000 (3.6 vs. 7.5 years).The present study showed a marked diagnostic delay among Japanese patients with AS. Although it has been improved, continuing medical education focusing on inflammatory back pain in adolescent is required for early diagnosis of AS.

Femur deformities can make stem fixation difficult in total hip arthroplasty (THA). We report the clinical results of cementless THA using a press-fit stem in patients who had previously undergone femoral osteotomy for hip dysplasia. The subjects included 66 hips in 64 patients, with the mean follow-up period of 7.3 years. THA was performed at a mean period of 17.1 years after intertrochanteric femoral osteotomy. Valgus osteotomy was performed in 42 hips, and varus osteotomy in 24. Clinical results were evaluated by using the Merle d’Aubigne-Postel score. Implant survival was determined with revision as the end point, and any related complications were investigated. The Merle d’Aubigne-Postel score improved from 9.4 to 16.1 at the final follow-up, without any implant loosening. However, periprosthetic femoral fractures were observed in four hips (6.0 %), one intra-operatively and three within three weeks after THA. Among these cases, three hips previously had varus osteotomy (12.5 %) and one hip had valgus osteotomy (2.3 %). Two hips were revised with full porous stems and circumferential wiring. The five and ten year cumulative survivorship rates were 97 % (range, 88.8–99.3 %) and 97 % (88.8–99.3 %), respectively. Although the use of a press-fit cementless stem yielded acceptable results in most of the patients, perioperative femoral fracture was a major complication especially in the patients previously treated with intertrochanteric varus osteotomy. Careful planning and implant selection could be emphasized for these cases.

Objective To establish a method to culture synovial tissue explants from patients with rheumatoid arthritis (RA). Methods Synovial tissue explants obtained from 10 patients with RA were cultured at the air–liquid interface or were submerged in culture medium. As a control, synovial explants were engrafted subcutaneously into SCID mice. The synovial explants were harvested at different time points, and histologic or flow cytometric analysis was performed. Cytokine levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Infliximab was added to the air–liquid interface culture to evaluate the effect of tumor necrosis factor α blockade on inflammatory cytokine production. Results The histologic features of RA synovitis, including a hyperplastic lining layer and the presence of cellular infiltrate in the sublining layer, were maintained in synovial tissue explants in air–liquid interface culture. In synovial grafts harvested from SCID-HuRAg mice, the cellular infiltrate was well maintained in the sublining, but the lining layer was lost. Viable CD4+ T cells and macrophages were abundant after air–liquid interface culture but were virtually absent after submerged culture. Furthermore, synovial tissue explants in air–liquid interface culture produced interleukin-6 (IL-6) and IL-8 for a prolonged period of time. The addition of infliximab effectively reduced cytokine production. Conclusion RA synovial explants can be maintained for weeks using an air–liquid interface culture. This simple culture system might be useful for analyzing the pathogenesis of RA synovitis and for developing antirheumatic drugs.

Case A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD. Conclusion MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy.

Purpose: Fragility hip fractures (FHFs) are associated with a high risk of mortality, but the relative contribution of various factors remains controversial. This study aimed to evaluate predictive factors of mortality at 1 year after discharge in Japan. Methods: A total of 497 patients aged 60 years or older who sustained FHFs during follow-up were included in this study. Expected variables were finally assessed using multivariable Cox proportional hazards models. Results: The 1-year mortality rate was 9.1% (95% confidence interval: 6.8–12.0%, n = 45). Log-rank test revealed that previous fractures ( p = 0.003), Barthel index (BI) at discharge ( p = 0.011), and place-to-discharge ( p = 0.004) were significantly associated with mortality for male patients. Meanwhile, body mass index (BMI; p = 0.023), total Charlson comorbidity index (TCCI; p = 0.005), smoking ( p = 0.007), length of hospital stay (LOS; p = 0.009), and BI ( p = 0.004) were the counterparts for females. By multivariate analyses, previous vertebral fractures (hazard ratio (HR) 3.33; p = 0.044), and BI 2 (HR 2.70, p = 0.023), TCCI ≥5 (HR 2.61, p = 0.032), smoking history (HR 3.59, p = 0.018), LOS Conclusions: Previous vertebral fractures and BI 2, TCCI ≥5, smoking history, LOS

This study was conducted to assess the posterior inclination of the contralateral femoral epiphysis in patients with unilateral slipped capital femoral epiphysis (SCFE).The posterior sloping angle (PSA) was measured using lateral radiographs in 67 patients with a unilateral SCFE and in 41 age-matched normal controls. A symptomatic epiphyseal slip was defined as the development of SCFE.The contralateral PSA in SCFE patients was more widely distributed and significantly larger compared to controls (15.0° vs. 9.0°, p 0.0001). Forty-seven hips (70.1%) had a PSA of greater than 12.8°, which was +2SD of the control hips. Of the 65 hips excluding the two cases with prophylactic pinning, 11 hips (16.9%) eventually developed a contralateral SCFE during adolescence and their PSA at the initial visit was significantly larger compared to patients without a contralateral SCFE (18.0° vs. 14.3°, p 0.005) with a cutoff value of 19°.These findings suggested the possibility of bilateral hip involvement in SCFE patients. Hips with greater degrees of PSA (19°) are likely to become symptomatic.

This study was conducted to examine the risk factors for recurrent dislocation after total hip arthroplasty (THA) and test the hypothesis that late dislocations are associated with recurrence.A total of 1,250 hips in 1,017 patients were retrospectively reviewed. All operations were performed through the posterolateral approach with posterior soft tissue repair. An early or late dislocation was defined as a dislocation occurring before or after one year postoperatively, respectively.Dislocation occurred in 36 hips (2.9 %) and 20 of them experienced recurrence. Recurrent dislocations were observed in ten out of 25 hips (40.0 %) with early dislocation; however, ten out of 11 hips (90.9 %) with late dislocation experienced recurrence (p = 0.0046). Multivariate analysis revealed that late dislocation was significantly associated with recurrence with odds ratio of 5.94 per year. Seven in 20 hips with recurrent dislocation required surgical treatment.Late dislocation significantly contributed to the development of recurrent dislocations.

The purpose of this study was to examine the effects of ceramic femoral head material on the wear of annealed, crosslinked ultra-high molecular weight polyethylene (UHMWPE) (XLPE) in total hip arthroplasty compared to non-crosslinked conventional UHMWPE (CPE). XLPE was fabricated by crosslinking with 60 kGy irradiation and annealing. Femoral heads made from zirconia and alumina ceramics, and cobalt-chrome (CoCr) of 22 mm or 26 mm diameter were used. In this study, the femoral head penetration into the cup was measured digitally on radiographs of 70 hips with XLPE and 50 hips with CPE. The average follow-up periods were 6.1 and 12.7 years, respectively. The steady wear rate of XLPE was significantly lower than those of CPE (0.002 versus 0.08 mm/year, respectively). Zirconia displayed increased wear rates compared to alumina in CPE; however, there was no difference among head materials in XLPE (0.0028, 0.011 and 0.009 mm/year for zirconia, alumina and CoCr, respectively). Neither head size or implantation period impacted XLPE wear. In contrast to CPE, XLPE displayed low wear rates surpassing the effects of varying femoral head material, size, implantation period and patient demographics.

Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent with this observation, mice expressing constitutively active parathyroid hormone (PTH)/PTH-related peptide receptors (PPR) in osteoblasts (PPR*Tg) display BM fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a double-mutant mouse expressing constitutively active PPR and green fluorescent protein (GFP) under the control of the type I collagen promoter (PPR*Tg/GFP) was generated. Confocal microscopy and flow cytometry revealed the presence of a cell population expressing GFP (GFP(+)) that was also positive for the hematopoietic marker CD45 in the BM of both PPR*Tg/GFP and control animals. This cell population was expanded in PPR*Tg/GFP. The existence of cells expressing both type I collagen and CD45 in the adult BM was confirmed by IHC and fluorescence-activated cell sorting. An analysis of total RNA extracted from sorted GFP(+)CD45(+) cells showed that these cells produced type I collagen and PTH/PTH-related peptide receptor and receptor activator for NF-κB mRNAs, further supporting their features of being both mesenchymal and hematopoietic lineages. Similar cells, known as fibrocytes, are also present in pathological fibroses. Our findings, thus, indicate that the BM is a permissive microenvironment for the differentiation of fibrocyte-like cells and raise the possibility that these cells could contribute to the pathogenesis of BM fibrosis.

SummaryStem cell population size is highly regulated across species and tissue types, and alterations are associated with premature tissue failure or cancer. We assessed whether the tumor suppressor and mediator of cell contact inhibition Nf2/merlin plays a role in governing the hematopoietic stem cell pool by stem cell-autonomous or niche-determined processes. Hematopoietic stem cells in Nf2-deficient mice were increased in number and demonstrated a marked shift in location to the circulation. These changes were entirely dependent on changes in the microenvironment, with a marked increase in trabecular bone and marrow vascularity associated with increased VEGF, but without cell-autonomous alterations in stem cell characteristics. Nf2/merlin is critical for maintaining normal structure and function of the hematopoietic stem cell niche. It limits both bone and vascular components, and our model suggests that it thereby constrains stem cell number and position.

Background: Along with the recent advances in the pharmacological management of rheumatoid arthritis, there is a trend toward the use of joint-preserving surgery in the treatment of rheumatoid forefoot deformities. However, the clinical outcomes of joint-preserving surgery for rheumatoid forefoot deformities have not been assessed in comparison to resection arthroplasty. Methods: We retrospectively evaluated 23 feet in 17 patients with rheumatoid forefoot deformities who underwent surgery between January 2010 and December 2013. The patients included 1 male (1 foot) and 16 females (22 feet), with a mean age of 62 years. The mean length of follow-up was 28 months. The patients were treated by 3 surgeons. One surgeon performed joint-preserving procedures (JP group) to the feet in which (1) no pain with motion existed, and (2) the range of motion in the first metatarsophalangeal (MTP) joint was greater than 30 degrees (n = 10); otherwise, resection arthroplasty with arthrodesis of the first MTP joint was performed (n = 3). The other surgeons performed resection arthroplasty in all cases (n = 10) (RA group, n = 13 in total). The clinical outcomes of the patients were evaluated using the Japanese Society for Surgery of the Foot (JSSF) hallux and lesser toe scales. Results: There were no significant differences in the preoperative total JSSF scores for either the hallux (54.5 and 61.4 points) or the lesser toe (45.2 and 57.4 points) between the RA and JP groups, respectively. Postoperatively, the total JSSF scores for both the hallux (79.4 and 88.2 points) and lesser toes (73.6 and 87.7 points) showed significant improvement in both the RA and JP groups, respectively; however, the JP group showed a greater postoperative improvement. The scores relating to the function category on the hallux scale and the alignment category on the lesser toe scale were significantly higher in the JP group. Conclusion: With regard to the function of the hallux and the alignment of the lesser toes, the joint-preserving procedures for rheumatoid forefoot deformities resulted in better clinical outcomes than resection arthroplasty. Level of Evidence: Level III, comparative case series.

Total hip arthroplasty (THA) is often performed in the lateral decubitus (lateral) position. In this position, the pelvis may have various degrees of tilt leading to implant malposition. We sought to quantify the pelvic tilt in lateral position and further pelvic movement during surgery.In 95 cases with primary THA, three-dimensional pelvic tilts were quantified by superimposing images reconstructed from CT data onto antero-posterior radiographs taken in lateral position at set-up and after cup placement. Pelvises were fixed with a device compressing anterior superior iliac spines and sacrum.Various degrees of pelvic tilt occurred compared to the supine position; sagittal: -3.1° (-25.5° to 10.2°), axial: 3.9° (-8.4° to 17°), coronal: 0.9° (-11.9° to 13.2°). Absolute changes more than 5° were observed 43%, 47%, and 12% in the sagittal, axial, and coronal planes, respectively. The more preoperative posterior pelvic tilt resulted in the more change in the sagittal plane. Further pelvic movement of about 3° in three planes were observed ranging from -11° to 20° after cup placement.This study showed various pelvic tilt and movement during THA. As pelvic tilt directly alters the cup orientation, its changes should be well understood. Improved tools for positioning and holding the pelvis are required.

A 37-year-old female had been treated with corticosteroids for systemic lupus erythematosus clinically diagnosed at age 10. She suddenly had right hip pain without any antecedent trauma. Four months after the onset of pain, she visited her primary care physician. On magnetic resonance imaging, joint space narrowing at the weight-bearing area was already seen with bone marrow edematous lesions in both the femoral head and acetabulum. She was treated non-operatively; however, her pain continued to worsen in severity. Thirteen months after the onset of pain, she was referred to our hospital. A plain radiograph showed subluxation of the collapsed femoral head accompanied by destruction of the acetabular rim. Because of her severe intractable pain, she underwent total hip arthroplasty 1 month after her first visit. Histological examination of the resected femoral head revealed pseudogranulomatous lesions along with prominent callus formation, suggesting rapid destruction of the femoral head.

Introduction: Preventing post-traumatic osteoarthritis is a challenging problem following acetabular fracture. Progressive osteoarthritis is considered to be caused by an irregular articular surface of the acetabular roof or cartilage injury, but little is known about the pathogenesis of collapse of the femoral head after acetabular fracture. We report a case of post-traumatic osteoarthritis after acetabular fracture in which subchondral fracture of the femoral head contributed to the progressive collapse of the femoral head and osteoarthritis. To the best of our knowledge, there has been no previous report of subchondral fracture of the femoral head after acetabular fracture. Case presentation: A 58-year-old Japanese man fell from a ladder. He was diagnosed with a left acetabular fracture, which was managed conservatively. He developed left coxalgia six months after injury and was seen at our institution one year after the onset of pain. The left acetabular fracture had fused, but his left femoral head had collapsed. The images at the time of injury showed a fracture of the acetabular roof, and an approximately 2mm step-off existed in the articular surface. Retrospective evaluation of the plain radiographs and computed tomography images showed that his femoral head had progressively collapsed. Our patient underwent total hip arthroplasty. Histopathologic findings demonstrated that the collapse of his femoral head was caused by a subchondral fracture of his femoral head. Conclusion: Our experience with this case indicates that in addition to post-traumatic osteonecrosis, subchondral fracture may need to be considered in cases with progressive collapse of the femoral head after acetabular fracture.

OBJECTIVE The aim of the study was to assess the degree and location of the reparative process in early osteonecrosis of the femoral head on the basis of single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m hydroxymethylene diphosphonate. MATERIALS AND METHODS This study was approved by the institutional review board. We retrospectively evaluated SPECT/CT scans of 23 consecutive hips. On the basis of the classification system used, 12 hips were classified as stage 1 (no radiographic abnormality), six hips as stage 2 (demarcating sclerosis without femoral head collapse), and five hips as stage 3A (

To establish a method to culture synovial tissue explants from patients with rheumatoid arthritis (RA).Synovial tissue explants obtained from 10 patients with RA were cultured at the air-liquid interface or were submerged in culture medium. As a control, synovial explants were engrafted subcutaneously into SCID mice. The synovial explants were harvested at different time points, and histologic or flow cytometric analysis was performed. Cytokine levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Infliximab was added to the air-liquid interface culture to evaluate the effect of tumor necrosis factor α blockade on inflammatory cytokine production.The histologic features of RA synovitis, including a hyperplastic lining layer and the presence of cellular infiltrate in the sublining layer, were maintained in synovial tissue explants in air-liquid interface culture. In synovial grafts harvested from SCID-HuRAg mice, the cellular infiltrate was well maintained in the sublining, but the lining layer was lost. Viable CD4+ T cells and macrophages were abundant after air-liquid interface culture but were virtually absent after submerged culture. Furthermore, synovial tissue explants in air-liquid interface culture produced interleukin-6 (IL-6) and IL-8 for a prolonged period of time. The addition of infliximab effectively reduced cytokine production.RA synovial explants can be maintained for weeks using an air-liquid interface culture. This simple culture system might be useful for analyzing the pathogenesis of RA synovitis and for developing antirheumatic drugs.

To investigate the impact of adalimumab on the biologic-naive (bio-naïve) and bio-switch rheumatoid arthritis (RA) patients, and to clarify the appropriate indications for adalimumab treatment.The retention rate, efficacy and safety of adalimumab in twenty-one RA patients were analyzed. Fourteen of the patients were bio-naive and seven were bio-switched from other biologics. Concomitant methotrexate was used in 85% of the bio-naive and 71% of the bio-switch patients. The radiographic findings before and after the 1 year and the two years treatment were also surveyed.In the bio-naive group, 63% of patients continued adalimumab for 2 years, and remission was achieved in approximately 50% of patients. The mean 28-joint Disease Activity Scores improved from 5.2 to 2.6. Radiographically, the joint damage did not progress in either erosions or joint space narrowing. In the bio-switch group, the retention rate was 29%, and only patients who were switched from infliximab showed responses to the treatment. Herpes zoster requiring hospitalization occurred in two cases and injection site reactions were noted in other two cases.Adalimumab combined with methotrexate would be a useful first choice biologic regimen in bio-naïve RA patients. As a second biologic, adalimumab could be useful only when treatments are switched from infliximab.

Stem version is not always equivalent to femoral neck version (native version) in cementless total hip arthroplasty (THA). We therefore examined the discrepancy of version between the native femoral neck and stem using pre- and postoperative computed tomography (CT), the level of the femur where the canal version most closely fit the stem version, and the factors influencing version discrepancy between the native femoral neck and stem.A total of 122 hips in 122 patients who underwent primary THA using a metaphyseal-fit stem through the postero-lateral approach were included. Pre- and postoperative CT images were utilized to measure native and stem version, and the version of the femoral canal at four levels relative to the lesser trochanter.The mean native and stem versions were 28.1 ± 11.0° and 38.0 ± 11.2°, respectively, revealing increased stem version with a mean difference of 9.8° (p0.0001). A total of 84 hips (68.9 %) revealed an increase in version greater than 5°. Femoral canal version at the level of the lesser trochanter most closely approximated that of stem version. Among the factors analysed, both univariate and multivariate analysis showed that greater degrees of native version and anterior stem tilt significantly reduced the version discrepancy between the native femoral neck and stem version.Since a cementless stem has little version adjustability in the femoral canal, these findings are useful for surgeons in preoperative planning and to achieve proper component placement in THA.

Sea-dyke is sometimes constructed, so one part of bay has been enclosed. This kind of situation is also observed at Isahaya of Nagasaki, that is a big project of construction of sea-dyke and reclamation. In order to make clean the enclosed water bodies, integrated management based on rivers and watershed should also be emphasized. On this viewpoint, pollutant runoff analysis by means of the Digital Elevation Model (DEM) has been carried out, and how to make available the water environmental management has been discussed, considering the environmental changes around at the enclosed sea area.Following to the purpose described above, in this paper, runoff rate of nitrogen from the watershed has been estimated, using the two-dimensional model of pollutant runoff by DEM. Even though parameter included in the model should be identified based on a lot of field data, it has been shown that proposed model might be useful for the prediction and control of non-point pollutant sources distributed over the watershed.

We examined the remodelling of the femoral head-neck junction in patients with slipped capital femoral epiphysis (SCFE) and the frequency of residual cam deformities.We reviewed 69 hips in 56 patients with stable SCFE who had undergone in situ pinning. Mean age at slip was 11.7 years and the follow-up period 63.4 months. Cam deformity was evaluated using the anterior offset alpha (α) angle and head-neck offset ratio (HNOR).The average α angle and HNOR significantly improved from 76.2° to 51.3° and 0.086 to 0.135, respectively; 25 hips (36.2%) still had an α angle greater than 50°, and 32 hips (46.4%) had an HNOR of under 0.145. A multivariate analysis selected age at onset and slip angle as risk factors for cam deformity, with cutoff values 11.1 years and 21.0°, respectively.Although most hips had remodelling of the head-neck junction, 29.4 % had residual cam deformities that may be susceptible to femoroacetabular impingement.

The purpose of this study was to report results at a minimum of 10 years for hydroxyapatite (HA) coating on the titanium arc-sprayed cementless total hip arthroplasty (THA) and to evaluate the impact of cross-linked polyethylene (XLPE) on implant longevity. A total of 131 consecutive primary THAs in 123 patients using an AMS acetabular cup and a PerFix HA stem were retrospectively reviewed. Conventional PE was used for 62 hips (CPE group) and cross-linked PE for 69 hips (XLPE group), with mean follow-up periods of 13 and 11.5 years, respectively. These patients were reviewed using the Japanese Orthopaedic Association (JOA) Hip Score and evaluated in terms of PE wear, osteolysis, and implant survival. The JOA score improved from 42.6 to 83.9 points at the final follow-up. The mean wear rate of 0.12 mm/year in the CPE group was significantly greater than that of XLPE at 0.007 mm/year. In the CPE group, ten (16.1 %) and two (3.2 %) hips, respectively, underwent PE exchange due to severe wear and acetabular revision due to loosening associated with osteolysis. Three patients had revision in the XLPE group: one cup for aseptic loosening, one PE for recurrent dislocation, and one stem for neck fracture. No evident osteolysis was seen in the XLPE group. Kaplan–Meier survivorship with any revision as the end point shows that the 12-year survival rate was 97.7 % for cups, 93.8 % for PE liners, and 99.2 % for stems. Multivariate analysis revealed that the use of XLPE significantly reduced the risk of revision, with the odds ratio (OR) of 4.3. AMS and PerFix HA components in this series show excellent implant fixation; however, high rates of PE wear and subsequent osteolysis were limiting factors in long-term success. Low wear rates with XLPE suggest improved implant longevity.

The purpose of this study was to examine the effects of ceramic femoral head material, size, and implantation periods on the wear of annealed, cross-linked ultra-high molecular weight polyethylene (UHMWPE) (XLPE) in total hip arthroplasty compared to non-cross-linked conventional UHMWPE (CPE). XLPE was fabricated by cross-linking with 60 kGy irradiation and annealing. Femoral heads made from zirconia and alumina ceramics and cobalt-chrome (CoCr) of 22 or 26 mm diameter were used. In this retrospective cohort study, the femoral head penetration into the cup was measured digitally on radiographs of 367 hips with XLPE and 64 hips with CPE. The average follow-up periods were 6.3 and 11.9 years, respectively. Both XLPE creep and wear rates were significantly lower than those of CPE (0.19 mm vs. 0.44 mm, 0.0001 mm/year vs. 0.09 mm/year, respectively). Zirconia displayed increased wear rates compared to alumina in CPE; however, there was no difference among head materials in XLPE (0.0008, 0.00007, and -0.009 mm/year for zirconia, alumina, and CoCr, respectively). Neither head size or implantation period impacted XLPE wear. In contrast to CPE, XLPE displayed low wear rates surpassing the effects of varying femoral head material, size, implantation period, and patient demographics. Further follow-up is required to determine the long-term clinical performance of the annealed XLPE.

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).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.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 gap1 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.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.

Objective Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). The aim of this study was to examine the effects of tofacitinib in vitro and in vivo in RA, in order to elucidate the role of JAK in the disease process. Methods CD4+ T cells, CD14+ monocytes, and synovial fibroblasts (SFs) were purified from the synovium and peripheral blood of patients with RA and were evaluated for the effect of tofacitinib on cytokine production and cell proliferation. For in vivo analysis, synovium and cartilage samples obtained from patients with RA were implanted in immunodeficient mice (SCID-HuRAg mice), and tofacitinib was administered via an osmotic minipump. Results Tofacitinib treatment of CD4+ T cells originating from synovium and peripheral blood inhibited the production of interleukin-17 (IL-17) and interferon-γ (IFNγ) in a dose-dependent manner, affecting both proliferation and transcription, but had no effect on IL-6 and IL-8 production. Tofacitinib did not affect IL-6 and IL-8 production by RASFs and CD14+ monocytes. However, conditioned medium from CD4+ T cells cultured with tofacitinib inhibited IL-6 production by RASFs and IL-8 production by CD14+ monocytes. Treatment of SCID-HuRAg mice with tofacitinib decreased serum levels of human IL-6 and IL-8 and markedly suppressed invasion of synovial tissue into cartilage. Conclusion Tofacitinib directly suppressed the production of IL-17 and IFNγ and the proliferation of CD4+ T cells, resulting in inhibition of IL-6 production by RASFs and IL-8 production by CD14+ cells and decreased cartilage destruction. In CD4+ T cells, presumably Th1 and Th17 cells, JAK plays a crucial role in RA synovitis.

Intracortical porosities and marrow fibrosis are hallmarks of hyperparathyroidism and are present in bones of transgenic mice expressing constitutively active parathyroid hormone/parathyroid hormone-related protein receptors (PPR*Tg). Cortical porosity is the result of osteoclast activity; however, the etiology of marrow fibrosis is poorly understood. While osteoclast numbers and activity are regulated by osteoprotegerin (OPG), bisphosphonates suppress osteoclast activity but not osteoclast numbers. We therefore used OPG and bisphosphonates to evaluate the extent to which osteoclasts, as opposed to bone resorption, regulate marrow fibrosis in PPR*Tg mice after treatment of animals with vehicle, OPG, alendronate, or zoledronate. All three agents similarly increased trabecular bone volume in both PPR*Tg and control mice, suggesting that trabecular bone resorption was comparably suppressed by these agents. However, the number of trabecular osteoclasts was greatly decreased by OPG but not by either alendronate or zoledronate. Furthermore, intracortical porosity and marrow fibrosis were virtually abolished by OPG treatment, whereas alendronate and zoledronate only partially reduced these two parameters. The greater reductions in cortical porosity and increments in cortical bone mineral density with OPG in PPR*Tg mice were associated with greater improvements in bone strength. The differential effect of OPG versus bisphosphonates on marrow fibrosis, despite similar effects on trabecular bone volume, suggests that marrow fibrosis was related not only to bone resorption but also to the presence of osteoclasts.

Following the identification of bone marrow multipotent cells that could adhere to plastic and differentiate along numerous mesenchymal lineages in vitro, a considerable effort has been invested in characterizing and expanding these cells, which are now called "mesenchymal stem cells" (MSCs), in vitro. Over the years, numerous lines of evidence have been provided in support of their plasticity, their extraordinary immunomodulatory properties, their potential use for tissue engineering purposes, as well as their ability to be recruited to sites of injury, where they might contribute a "natural in vivo system for tissue repair." Moreover, some studies have attempted the characterization of their cell-surface specific antigens and of their anatomical location in vivo. Lastly, it has been shown that similar cells could be also isolated from organs other than the bone marrow. Despite this impressive body of investigations, numerous questions related to the developmental origin of these cells, their proposed pluripotency, and their role in bone modeling and remodeling and tissue repair in vivo are still largely unanswered. In addition, both a systematic phenotypic in vivo characterization of the MSC population and the development of a reproducible and faithful in vivo assay that would test the ability of MSCs to self-renew, proliferate, and differentiate in vivo are just beginning. This brief review summarizes the current knowledge in the field of study of MSCs and the outstanding questions.

Bone metabolism and the immune system have a correlative relationship, and both are controlled by various common cytokines, such as IFNs and ILs, produced in the bone microenvironments. The suppressor of cytokine signaling-1 (SOCS1) and SOCS3 are negative regulators of such cytokines. Although SOCSs are shown to be induced during osteoclast differentiation, their physiological roles in osteoclast differentiation and function have not been clarified. Thus, we examined the roles of SOCS1 and SOCS3 in osteoclastogenesis using SOCS1- and SOCS3-deficient mice. IFN-γ-mediated inhibition of osteoclast differentiation from bone marrow-derived monocytes (BMMs) was strongly enhanced in SOCS1-deficient BMMs, but was diminished in SOCS1-overexpressing BMMs. Moreover, LPS-induced osteoclastogenesis and bone destruction in vivo were suppressed in SOCS1+/− mice compared with those in wild-type mice, suggesting that SOCS1 antagonizes the inhibitory effect of IFN-γ on osteoclastogenesis. SOCS3 did not alter the inhibitory effect of IFNs in osteoclastogenesis in both gain and loss of functional assays; however, the suppressive effect of IL-6 on osteoclast differentiation was greater in SOCS3-deficient BMMs than in wild-type BMMs in vitro. In addition, IL-6 significantly prevented LPS-induced bone destruction in SOCS3-deficient mice, although it failed in wild-type mice in vivo. In SOCS3-deficient BMMs, expression levels of TNF-receptor-associated factor-6 and IκB were drastically reduced and receptor activator of the NF-κB ligand-induced IκB phosphorylation was severely impaired in the presence of IL-6. These data suggest that both SOCS1 and SOCS3 regulate osteoclastogenesis by blocking the inhibitory effect of inflammatory cytokines on receptor activator of the NF-κB ligand-mediated osteoclast differentiation signals. Selective suppression of SOCS1 and SOCS3 in osteoclast precursors may be a possible therapeutic strategy for inflammatory bone destruction.

Immune and inflammatory systems are controlled by multiple cytokines, including interleukins and interferons. These cytokines exert their biological functions through Janus tyrosine kinases and signal transducer and activator of transcription factors. The cytokine-inducible Src homology 2 protein (CIS) and suppressors of cytokine signaling (SOCS) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine responses, including those that regulate the inflammatory systems. In this short review, we focused on the molecular mechanism of the action of CIS/SOCS family proteins and their roles in Toll-like receptor signal regulation and inflammatory diseases.

Inflammation is progressed by the action of pro-inflammatory cytokines, including IL-1, TNF, IFN-gamma and IL-6, and is resolved by anti-inflammatory cytokines, such as IL-4, IL-10, IL-13, IFN-alpha and transforming growth factor-beta (TGF-beta). Intracellular signal transduction pathways initiated by these cytokines have been studied extensively; these pathways ultimately activate transcription factors, such as NF-kappa B, Smad and STATs. Recently, negative feedback regulation of these pathways, mediated by molecules such as A-20, Smad7 and CIS/SOCS family proteins, has been identified. Negative regulation of cytokine signaling is quite important for inflammation.

Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4. We show here that the suppressor of cytokine-signaling-1 (SOCS1/JAB) is rapidly induced by LPS and negatively regulates LPS signaling. SOCS1(+/-) mice or SOCS1(-/-) mice with interferon-gamma (IFNgamma)-deficient background were more sensitive to LPS-induced lethal effects than were wild-type littermates. LPS-induced NO(2)(-) synthesis and TNFalpha production were augmented in SOCS1(-/-) macrophages. Furthermore, LPS tolerance, a protection mechanism against endotoxin shock, was also strikingly reduced in SOCS1(-/-) cells. LPS-induced I-kappaB and p38 phosphorylation was upregulated in SOCS1(-/-) macrophages, and forced expression of SOCS1 suppressed LPS-induced NF-kappaB activation. Thus, SOCS1 directly suppresses TLR4 signaling and modulates innate immunity.

Background Although a substantial percentage of patients with rheumatoid arthritis (RA) experience low back pain, the characteristics of lumbar spine pathology in RA patients has been poorly investigated. In our institutions, lumbar spine radiographs indicated scoliosis in 26 patients. The present study aimed to clarify the characteristics of lumbar scoliosis in RA patients. Methods This is a retrospective study of 26 RA patients with lumbar scoliosis. Patient characteristics such as disease duration, disease stage and class according to Steinbrocker's classification, and medication for RA and osteoporosis were reviewed. Radiologic evaluation of scoliosis was performed at two different time points by measuring Cobb angles. The progression of scoliosis per year was calculated by dividing the change in Cobb angles by the number of years. Apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at the first observation were also measured. The correlation between different factors and changes in the Cobb angles per year was analyzed. Results Majority of the patients had a long disease duration and were classified as stage 3 or 4 according to Steinbrocker's classification. During the observation period, most patients were treated with glucocorticoids. Unlike the previous studies on degenerative scoliosis, apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at initial observation were not significantly related to the progression of scoliosis. Initial Cobb angles were inversely related to the progression of scoliosis. Patients who were treated with bisphosphonates showed slower progression of scoliosis. Conclusions Our results indicate that the characteristics of lumbar scoliosis in RA patients differ from those of degenerative lumbar scoliosis. Bone fragility due to the long disease duration, poor control of disease activity, and osteoporosis is possibly related to its progression.