Knee dynamics during take-off and landing in spike jumps performed by volleyball players with patellar tendinopathy.

[Purpose] Patellar tendinopathy is a common sports injury. The risk factors for this injury can be categorized as intrinsic, extrinsic, and dynamic. We examined the dynamic factors in this study. [Participants and Methods] The participants were volleyball players who were assigned to a patient group (n=6) if they had medial patellar tendinopathy in the left knee or to a control group (n=7) otherwise. The participants performed spike jumps, and their ground reaction force and three-dimensional kinematic data were recorded. Knee angle and moment data were extracted at the peak extension moment of take-off and landing. [Results] The two groups showed no differences in knee angles. A tendency for abduction/external rotation moments at take-off and landing on both sides was observed in the control group, while the patient group showed adduction and internal rotation moments at take-off and adduction moment at landing in the left (injured) knee. [Conclusion] The observed knee joint moments in the left (injured) knee of the patient group may have been involved in the pathophysiological mechanism underlying the development of patellar tendinopathy.

Dynamic femoral head translations in dysplastic hips.

BACKGROUND: Developmental dysplasia of the hip is an important disease leading to osteoarthritis. Recently, researchers have focused on hip instability as a potentially important dynamic factor for osteoarthritis, but the detailed kinematics of dysplastic hips during weight-bearing gait have not been reported. The purpose of this research is to contrast femoral translation in contralateral healthy hips and dysplastic hips during weight-bearing stepping. METHODS: Twelve dysplastic hips and eight healthy hips were investigated. Hip joint kinematics were analyzed using 3D-2D model-image registration with dynamic fluoroscopic images of each hip during a stepping-in-place activity. Femoral translation relative to the acetabular center was quantified as instability. FINDINGS: Total femoral head translations were significantly different between dysplastic and contralateral healthy hips. Mean translation was 1.0mm in dysplastic hips and 0.4mm in contralateral healthy hips during swing-phase, and consisted of inferior translation during early swing phase with a complementary superior translation just before foot strike. Total femoral translation was significantly correlated to several radiographic indices of hip dysplasia. INTERPRETATION: Superior translations of the femur during the end of swing phase may result in altered articular contact mechanics, abnormal stresses on the labrum and lost lubricant sealing. All of these factors may contribute to joint degeneration and osteoarthritis in dysplastic hips.

Three-dimensional shape optimization of a cemented hip stem and experimental validations.

This study proposes novel optimized stem geometry with low stress values in the cement using a finite element (FE) analysis combined with an optimization procedure and experimental measurements of cement stress in vitro. We first optimized an existing stem geometry using a three-dimensional FE analysis combined with a shape optimization technique. One of the most important factors in the cemented stem design is to reduce stress in the cement. Hence, in the optimization study, we minimized the largest tensile principal stress in the cement mantle under a physiological loading condition by changing the stem geometry. As the next step, the optimized stem and the existing stem were manufactured to validate the usefulness of the numerical models and the results of the optimization in vitro. In the experimental study, strain gauges were embedded in the cement mantle to measure the strain in the cement mantle adjacent to the stems. The overall trend of the experimental study was in good agreement with the results of the numerical study, and we were able to reduce the largest stress by more than 50% in both shape optimization and strain gauge measurements. Thus, we could validate the usefulness of the numerical models and the results of the optimization using the experimental models. The optimization employed in this study is a useful approach for developing new stem designs.

Early weight-bearing after periacetabular osteotomy leads to a high incidence of postoperative pelvic fractures.

BACKGROUND: It has not been shown whether accelerated rehabilitation following periacetabular osteotomy (PAO) is effective for early recovery. The purpose of this retrospective study was to compare complication rates in patients with standard and accelerated rehabilitation protocols who underwent PAO. METHODS: Between January 2002 and August 2011, patients with a lateral center-edge (CE) angle of < 20°, showing good joint congruency with the hip in abduction, pre- or early stage of osteoarthritis, and age younger than 60 years were included in this study. We evaluated 156 hips in 138 patients, with a mean age at the time of surgery of 30 years. Full weight-bearing with two crutches started 2 months postoperatively in 73 patients (80 hips) with the standard rehabilitation protocol. In 65 patients (76 hips) with the accelerated rehabilitation protocol, postoperative strengthening of the hip, thigh and core musculature was begun on the day of surgery as tolerated. The exercise program included active hip range of motion, and gentle isometric hamstring and quadriceps muscle sets; these exercises were performed for 30 minutes in the morning and 30 minutes in the afternoon with a physical therapist every weekday for 6 weeks. Full weight-bearing with two axillary crutches started on the day of surgery as tolerated. Complications were evaluated for 2 years. RESULTS: The clinical results at the time of follow-up were similar in the two groups. The average periods between the osteotomy and full-weight-bearing walking without support were 4.2 months and 6.9 months in patients with the accelerated and standard rehabilitation protocols (P < 0.001), indicating that the accelerated rehabilitation protocol could achieve earlier recovery of patients. However, postoperative fractures of the ischial ramus and posterior column of the pelvis were more frequently found in patients with the accelerated rehabilitation protocol (8/76) than in those with the standard rehabilitation protocol (1/80) (P = 0.013). CONCLUSION: The accelerated rehabilitation protocol seems to have advantages for early muscle recovery in patients undergoing PAO; however, postoperative pelvic fracture rates were unacceptably high in patients with this protocol.

Intermediate- to long-term results after hybrid total hip arthroplasty in patients with rheumatoid arthritis.

There have been few reports describing intermediate- to long-term results after hybrid total hip arthroplasty in patients with rheumatoid arthritis. We followed up 52 hips in 44 patients aged 5 men and 39 women, with a mean of 11.5 years (range, 5-23.5 years). Revisions had been performed in 6 hips in 6 patients: 1 both acetabular and femoral components for infection, 1 acetabular component for aseptic loosening, 3 acetabular components for recurrent dislocation, and 1 acetabular component for dislodgement of the polyethylene liner from the metal shell. None of other acetabular or femoral components were revised or found to be loose at the final follow-up. Although postoperative dislocation remains a concern, hybrid total hip arthroplasty had an acceptable result in patients with rheumatoid arthritis.

Blockade of JNK and NFAT pathways attenuates orthopedic particle-stimulated osteoclastogenesis of human osteoclast precursors and murine calvarial osteolysis.

Particles released from orthopedic implants attract immune host defense cells to the bone-implant interface and contribute to development of inflammation. The inflammatory microenvironment supports recruitment and differentiation of osteoclasts, the primary culprit of osteolysis. Therefore, understanding the complex signals that contribute to osteoclastogenesis and osteolysis is a sensible approach to design strategies to inhibit bone loss. The signaling cascades that coordinate osteoclastogenesis have been widely investigated. These include MAP kinases, Akt/PI3K pathway, NF-κB signal transduction pathway, and NFAT pathway. We have recently reported that polymethylmethacrylate (PMMA) particles activate the NFAT pathway in murine osteoclast precursors and that NFAT inhibitors dose-dependently block PMMA-induced osteoclastogenesis. In the current study, we examined the role of JNK and NFATc1 in mice in response to PMMA particles using murine calvaria model. We show that locally administered MAPK/JNK inhibitor SP600125 and calcineurin/NFAT inhibitor cyclosporine-A effectively blocked PMMA-induced osteolysis in murine calvaria. To buttress the clinical relevance of JNK/NFATc1-based regulation of PMMA-induced osteoclastogenesis, we evaluated the effect of PMMA using human macrophages. We demonstrate that SP600125 and cyclosporine-A abolished particle-induced osteoclastogenesis in human osteoclast progenitors retrieved from patients undergoing total hip replacement. Thus JNK and NFATc1 appear to act as significant mediators of orthopedic particle-induced osteolysis in humans.

Epidemiology of degenerative lumbar scoliosis: a community-based cohort study.

STUDY DESIGN: A 12-year prospective study of pre-existing and de novo degenerative lumbar scoliosis (DLS) among community-based female volunteers. OBJECTIVE: To investigate serial entire spine radiographs of healthy female volunteers and to clarify radiographical characteristics and predictors of pre-existing and de novo DLS. SUMMARY OF BACKGROUND DATA: DLS is among the most frequent spinal defomities in the aging spine; however, the onset or the natural course of this condition has not been elucidated. METHODS: A total of 144 female volunteers were recruited from population register. Radiographical measurements using entire spine radiographs included thoracic kyphosis (T4-12), lumbar lordosis (LL) (L1-5), sacral inclination angle, pelvic incidence, sagittal balance (C7 plumb), coronal L4 endplate angle (L4 tilt), and scoliotic angle by Cobb method. More than 10° of scoliosis was diagnosed as DLS. L4 vertebral size was measured (divided by body height) as well as lateral osteophyte formation and lateral disc wedge angle. RESULTS: Mean baseline age and follow-up period were 54.4 years and 12.1 years, respectively. Pre-existing DLS (pre-DLS) was found in 42 subjects (29.2%) at baseline. Among pre-DLS, 11 subjects (26%) showed more than 5° progression in scoliosis. De novo DLS has developed in 30 subjects (29.4%) among those without baseline scoliosis.Cox proportional hazards models revealed younger age, smaller L4 size, lower LL, greater DLS angle, and L4 tilt at baseline to be the risk factors of progression of pre-DLS and smaller L4 size, unilateral osteophyte formation, and lateral disc wedging to the risk of development of de novo DLS. CONCLUSION: This study indicated that younger age, smaller L4 size, lower LL, greater DLS angle, and L4 tilt at baseline should be evaluated as predictors of progression of pre-DLS. Early signs of asymmetric disc degeneration and smaller L4 size should also be evaluated as predictors of development of de novo DLS.

Radiological classification of glenoid deformity in rheumatoid arthritis.

We report a classification system based on the changes in shape of the glenoid fossa and on an evaluation of the upward migration of the humeral head, because a simple classification based on X-ray evaluation would be of great assistance to physicians dealing with the diagnosis and treatment of RA. We evaluated 150 shoulders of 118 RA patients who showed changes in the glenoid fossa after radiological examinations. The morphology of the glenoid fossa of the RA shoulder was classified into 3 types and we were able to classify a total of six types of deformities by adding the problem of upward migration of the humeral head. An additional investigation on the difference in the type of deformity between the right and left shoulder, the changes in type during the course of the study, and the relationship between this particular classification and certain patient characteristics was also included.

Intermediate to long-term results of periacetabular osteotomy in patients younger and older than forty years of age.

BACKGROUND: The treatment of middle-aged patients with periacetabular osteotomy remains controversial. The goal of the present retrospective study was to analyze the intermediate to long-term functional and radiographic results of periacetabular osteotomy in patients below and above the age of forty years. METHODS: Between February 1990 and December 2004, 166 periacetabular osteotomies were performed in 146 patients. We evaluated 158 hips in 139 patients who had a mean age of thirty-two years at the time of surgery. The mean duration of follow-up was eleven years (range, five to twenty years). We compared thirty-six patients (forty-one hips) who were forty years of age or older with 103 patients (117 hips) who were younger than forty years of age at the time of surgery. RESULTS: The average Harris hip score increased from 70 points preoperatively to 90 points postoperatively. The mean Harris hip scores at the time of the five-year follow-up were similar in the older and younger groups (p = 0.57), although the latest follow-up scores were significantly higher in the younger group than in the older group (91 compared with 88 points; p = 0.02). The average modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (with 0 representing the worst score and 100 representing the best score) was higher for the younger group than for the older group (92 compared with 90 points; p = 0.03). Kaplan-Meier analysis with progression of the Tönnis grade of osteoarthritis as the end point showed a ten-year survival rate of 90.8% (95% confidence interval, 88.3% to 93.3%) and a fifteen-year survival rate of 83.0% (95% confidence interval, 78.5% to 87.5%); the ten-year survival rates in the younger and older groups were 94.4% and 81.3%, respectively, and the fifteen-year survival rates were 86.9% and 71.2%, respectively (p = 0.025). CONCLUSIONS: Periacetabular osteotomy yielded similar results for the two groups at the time of the five-year follow-up, although the results for the older group deteriorated thereafter. Decrease in physical function due to aging and increased susceptibility to the progression of osteoarthritis may be responsible for the poorer results over time in the older group.

Supplemental treatment of rheumatoid arthritis with natural milk antibodies against enteromicrobes and their toxins: results of an open-labelled pilot study.

BACKGROUND: Environmental factors, particularly commensal bacteria in the gastrointestinal tract, may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to evaluate whether natural milk antibodies against a wide spectrum of pathogenic enteromicobes and their toxins modify the disease activity in RA. METHODS: Twenty patients with RA, whose disease activity was uncontrolled by authentic medications due to drug resistance, complications and/or risk factors were treated for 3 months with an oral administration of a whey protein concentrate (WPC) containing high levels of natural milk antibodies. Eighteen background-matched RA patients, not supplemented with milk antibody adjunct, were used as controls. RESULTS: Statistically significant reduction of arthritis symptoms and improvement of intestinal disorders were observed only in the test group: effective in 8 (44%), possibly effective in 2 (12%) and not effective in 8 (44%) of 18 patients treated (2 patients withdrew) based on an ad hoc "evaluation point", the sum of variables that are improved more than 20% among the 8 core variables used for the American College of Rheumatology (ACR) response criteria. This disease modifying effect of the WPC disappeared upon cessation of treatment, but was reappeared upon reintroduction of it. Importantly, 7 of 8 non-responders carry DR15 haplotype (DRB1-1501 and 1502), whereas only 1 of 7 responders was DR15 positive (risk ratio: 6.1). Furthermore, the pre-clinical serum anti-LPS and anti-type II collagen antibody levels in the responders were higher or tended to be higher than those in the non-responders, suggesting that there are 2 sub-types of RA based on an interaction between gastrointestinal pathogens and MHC class II haplotypes. CONCLUSIONS: The natural milk antibody preparation containing high levels antibodies against pathogenic enteromicrobes and their toxins seems to be effective in a certain RA subset, and deserves more attention as a potential adjunct in the treatment of RA. TRIAL REGISTRATION NUMBER: UMIN000003128.

Cemented calcar replacement femoral component in revision hybrid total hip arthroplasty.

We evaluated intermediate-term to long-term survival of cemented calcar replacement femoral components in hybrid revision total hip arthroplasty. We followed up 52 hips in 50 patients for a mean of 11.4 years. Six (12%) femoral components had been revised: 2 for aseptic loosening, 2 for periprosthetic fracture, and 2 for deep infection. One additional femoral component was definitely loose. The number of previous revision operations (P = .004), preoperatively poorer femoral bone stock (P = .005), and postoperative poor cement mantle grading (P = .003) were significant factors for failure. Kaplan-Meier analysis revealed that the 15-year survival rate was 90% with mechanical failure as the end point. This technique remains a reasonable option for the first-time revision, especially for older and less active patients.

Hybrid total hip arthroplasty using specifically-designed stems for patients with developmental dysplasia of the hip. A minimum five-year follow-up study.

A 4-U hybrid total hip arthroplasty (THA) system was specifically designed for patients with developmental dysplasia of the hip (DDH). Straight stem with an appropriate offset and various size variations are advantages. We followed 128 hips in 124 patients, 13 men and 111 women, for a mean of 6.5 years (range, 5.0-7.5 years). Two acetabular and femoral components in two patients had been revised for infection, one acetabular component had been revised for recurrent dislocation, and one femoral component had been revised for periprosthetic femoral fracture. None of the acetabular or femoral components were revised for loosening or were found to be loose at follow-up. The Harris hip score increased from a preoperative average of 42 points to 88 points at the most recent follow-up. Primary THA using the 4-U system had a good mid-term result in patients with DDH. This system could be applied for all patients including those with the narrowest and deformed femurs.

Use of a deep polyethylene liner for the treatment of recurrent dislocation.

Modular component exchange is one of several viable options for treating instability after total hip arthroplasty (THA). Recently, we reported that polyethylene liners retrieved from stable THAs had significantly deeper cup articular geometry than liners retrieved from dislocated THAs. Modular liner exchange with implantation of a deeper cup articulation for the treatment of THA instability may be an option in certain cases. We describe the use of modular liner exchange with implantation of a custom polyethylene liner with a deepened articular geometry for surgical treatment of recurrent dislocation after primary THA in a 70 year old patient. The patient did not feel unstable and no symptoms of subluxation or dislocation have been experienced in the 3 years of follow-up subsequent to treatment. Surgeons should consider the articular geometry of the polyethylene liner as an important design parameter, and we recommend that deeper polyethylene liners be considered for treatment of recurrent dislocation after primary THA.

Radiographic analysis of newly developed degenerative spondylolisthesis in a mean twelve-year prospective study.

STUDY DESIGN: Prospective study of community-based female volunteers. OBJECTIVE: To investigate the incidence of newly developed degenerative spondylolisthesis (DS) among those without baseline deformity, and to clarify radiographic characteristics and predictors of DS. SUMMARY OF BACKGROUND DATA: There has been limited number of prospective studies of DS. Our on-going cohort study of healthy volunteers enabled long-term observation of highly susceptible perimenopause female subjects. METHODS: A final total of 142 female subjects without spondylolisthesis at baseline radiographs were included and followed up for more than 8 years. Standardized serial entire spine radiographs were used to measure spinopelvic alignment, including pelvic incidence (PI), vertebral inclination angle, disc height, vertebral size, and facet orientation. RESULTS: The incidence of newly developed DS was 12.7%. Comparison between DS and non-DS subjects demonstrated that DS subjects had significantly greater baseline lumbar lordosis, PI, vertebral inclination angle, and smaller vertebral size. Exaggerated lumbopelvic alignment was more prominent in L3-DS than in L4-DS, and L4-DS was associated with the decrease in L4/5 disc height. Multivariate analysis revealed that PI, L4 vertebral inclination, adjusted vertebral size, and facet sagittalization were independent predictors of the development of DS. CONCLUSION: This was the first study to confirm the relationship of PI and the development of DS in a long-term prospective observation. Proposed pathogenetic differences might explain the fact that L4-DS is far more prevalent than L3-DS. The development of DS could be predicted by baseline lumbopelvic morphology among the highly susceptible perimenopause women.

Spinal metastasis from lung cancer fifteen years after surgery presenting a pseudohemangioma appearance of the vertebra: a case report.

STUDY DESIGN: Case report. OBJECTIVE: To describe a case of solitary metastasis of the seventh thoracic vertebra (T7) from lung cancer 15 years after surgery. SUMMARY OF BACKGROUND DATA: Late recurrence of the bone over 5 years after curative surgery for lung cancer is highly exceptional. In addition, bone metastasis from lung cancer showing a coarse trabecular pattern of the vertebra on computed tomography (CT) is quite unusual. METHODS: A case of solitary metastasis of T7 from lung cancer 15 years after surgery showing a pseudohemangioma appearance of the vertebra on CT is presented. RESULTS: A 66-year-old man presented with a 2-month history of gradually progressed numbness and muscle weakness of the bilateral leg, with a more recently developed spastic gate. He had undergone a left lower lobectomy for lung cancer 15 years previously. Magnetic resonance imaging showed an ill-defined mass lesion involving the entire vertebral body of T7 with extension into the posterior element and surrounding soft tissue, which resulted in moderate spinal canal stenosis. CT showed a coarse trabecular pattern at T7 with a mild compression fracture. No other lesion was detected by whole-body CT and bone scintigraphy. Tumor resection and T5-T9 posterior spinal fusion had been performed, and a pathologic diagnosis of metastatic pulmonary adenocarcinoma of the bone was established. Additional radiation therapy (40 Gy) was added, and the patient recovered and continued to survive uneventfully at the 3-month follow-up. CONCLUSION: We have reported a rare case of solitary metastasis to T7 appearing 15 years after surgery for lung cancer. The incidence of lung cancer recurrence more than 5 years after surgery is exceedingly low; however, even in patients with lung cancer, late occurrence of bone metastasis should be considered and included in the differential diagnosis of a pseudohemangioma appearance of the vertebra.

Porous-coated cementless acetabular components without bulk bone graft in revision surgery.

We previously reported the average 9.3-year (range, 5-13 years) results of 74 patients (83 hips) with porous-coated acetabular components that were placed without bulk bone graft at revision surgery. Since the previous report, 7 patients (7 hips) died before the minimum follow-up of 10 years, and 1 patient (1 hip) was lost to follow-up. We now report the average 15.6-year (range, 10-20 years) results for 66 patients (75 hips). Three additional acetabular components were removed or revised again: 2 for infection and 1 for dislodgement of the polyethylene liner from the metal shell. Overall, 7 (7%) components required removal or repeat revision. No shell was revised for aseptic loosening, and none was categorized as loose during the entire follow-up period.

Changes in the sagittal spinal alignment of the elderly without vertebral fractures: a minimum 10-year longitudinal study.

BACKGROUND: Thoracic hyperkyphosis, or loss of lumbar lordosis, is often equated with osteoporosis because vertebral fractures are assumed to be a major causative factor. However, recent evidence suggests that up to one-half of the patients with hyperkyphosis have no evidence of underlying vertebral fracture. The shape characteristics of the intervertebral discs and their role in determining kyphotic curvature have been investigated. The spinal sagittal parameters and segmental disc angles of elderly subjects were examined during a longitudinal follow-up. METHODS: A total of 53 subjects (20 men, 33 women) without vertebral fractures during a more than 10-year follow-up were included in this study, undergoing standing lateral radiographs of the spine using 36-inch film at baseline and final follow-up. The mean age of the subjects was 63 years (range 50-77 years) at baseline and 75 years (range 62-88 years) at follow-up; and the mean follow-up period was 11 years 11 months. RESULTS: The lumbar lordosis and the sacral inclination angle decreased and the C7-plumbline distance increased with age. Among a total of 664 discs, 70 discs (10.5%) showed anterior wedging over 5 degrees at follow-up. In contrast, 39 discs (5.9%) showed posterior wedging over 5 degrees . The subjects had only discs with anterior wedging, decreased total lumbar lordosis, and the C7 plumbline displaced anteriorly. However, when the subjects had discs with posterior wedging, the C7 plumbline and sagittal spinal balance tended to be maintained. This compensatory mechanism was seen in younger subjects. CONCLUSIONS: A decrease in the total lumbar lordosis and the sacral inclination angle occurred with age. Increasing age correlated with a more forward sagittal vertical axis, depending on a decrease in the total lumbar lordosis. The cause of loss of lumbar lordosis in the subjects without vertebral fracture was anterior wedging of the segmental discs. Posterior wedging of the thoracic and lumbar segmental discs then could occur, compensating for the loss of lumbar lordosis.

Serological monitoring of progression of alveolar echinococcosis with multiorgan involvement by use of recombinant Em18.

Two cases of alveolar echinococcosis (AE) with multiple-organ involvement (the liver, lungs, and bone) were monitored by imaging and serology for 20 years. Resection of the bone lesion was complete in one case but incomplete in the other case. Albendazole treatment was markedly to moderately effective against hepatic and pulmonary AE lesions in both cases, whereas it had almost no effect against the bone lesion in one case. The results of the serological tests with recombinant Em18 antigen coincided with the clinical findings in each case. An enzyme-linked immunosorbent assay for the detection of immunoglobulin G (IgG) responses, especially IgG4 responses, is expected to be a real-time indicator of the dynamics of active AE.

Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retrospective comparison with methotrexate for Japanese rheumatoid arthritis patients.

We retrospectively compared treatment impact with leflunomide (LEF) or methotrexate (MTX) on retarding joint damage and clinical symptom including a 28-joint-count Disease Activity Score/erythrocyte sedimentation rate (DAS28-ESR) between two similar groups in patients with rheumatoid arthritis (RA) over an approximately 3-year treatment. One group included 29 patients treated with LEF alone (average dose 16.1 mg/day); the other group included 26 patients treated with MTX (average dose 7.4 mg/week) alone or combined with other disease-modifying antirheumatic drugs. At baseline, mean disease duration was 7.1 and 6.9 years, and mean DAS28-ESR was 5.79 and 5.69, respectively. The average DAS28-ESR improvement of 1.750 (from 5.79 to 4.04) in the LEF-treated group was significantly greater than the effect of 1.007 (from 5.69 to 4.68) seen in the MTX group (P = 0.0455), with the same results being observed on European League Against Rheumatism (EULAR) response criteria. Annual changes observed in Larsen score in total joints were 0.030 in the LEF group and 0.085 in the MTX group: LEF retards joint damage significantly better than MTX (P = 0.003). This inhibitory effect was better in small joints (P = 0.004) than in middle and large joints (P = 0.075). A negative correlation was noticed between improved DAS28-ESR and the progression of joint damage in the LEF group (r = -0.7068, P < 0.0001), whereas there was no correlation in the MTX group (r = -0.0311, P = 0.882). In daily clinical practice, LEF showed significant clinical and radiological improvement compared with the standard MTX regimen in Japan.