A multicentre study of clinical features and HLA typing in Japanese patients with ankylosing spondylitis.

OBJECTIVES: Due to the low prevalence of HLA-B27 and ankylosing spondylitis (AS) in Japan, rheumatologists have little experience with AS. We conducted a multicentre study to identify the characteristics and frequency of HLA-B types. METHODS: We analysed epidemiological and clinical data, blood tests, spine radiographs, and HLA-B types in Japanese AS patients. RESULTS: We evaluated 111 AS patients, predominantly men (82.9%). The mean age, disease onset, diagnosis, and time from onset to diagnosis were 43.7, 24.2, 36.0, and 11.6 years, respectively. Inflammatory low back pain was found in 96 cases (86.5%); peripheral arthritis in 59 (53.2%), enthesitis in 35 (31.5%), and dactylitis in 6 (5.4%). Extra-articular symptoms included uveitis, psoriasis, and inflammatory bowel disease in 41 (36.9%), 1 (0.9%), and 5 (4.5%) cases, respectively. HLA-B27 was positive in 83 cases (74.8%; odds ratio, 1146.0); and HLA-B48 in 9 (8.1%; odds ratio, 3.0). HLA-B27-positive patients were younger at onset and had a shorter diagnostic delay. CONCLUSIONS: AS clinical symptoms were almost the same as other countries except for the low coexistence of psoriasis. HLA-B27 positivity in Japanese patients was 78%. HLA-B27-positive patients were younger and diagnosed earlier. In addition to HLA-B27, a relationship with HLA-B48 was suggested.

Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry.

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.

Prevalence of spondyloarthritis symptom in inflammatory bowel disease patients: A questionnaire survey.

OBJECTIVES: We clarified the prevalence of spondyloarthritis (SpA) symptom in inflammatory bowel disease (IBD). METHODS: We performed the questionnaire survey of SpA symptom in IBD patients on their office visit. RESULTS: One hundred and thirty seven patients were evaluated. The SpA features group included 46 (33.6%) patients (32 Men). Among them there were 22 Crohn's disease (CD) patients and 24 ulcerative colitis (UC) patients. The patients had a mean age of 48.3 years with a mean disease duration of 12.3 years. Non-SpA group (66.4%) included 91 patients (49 Men). Among them there were 27 CD patients and 64 UC patients. The patients had a mean age of 43.3 years with a mean disease duration of 9.2 years. In univariate analysis, the SpA group (33.6%) had longer disease duration than non-SpA group (p < 0.05). However, age at onset and sex were not significantly different among the groups. Multivariate analysis showed that disease duration was independently associated with SpA symptom (OR, 1.05; 95% CI, 1-1.09; p = 0.036). CONCLUSIONS: The prevalence of SpA symptom was relatively higher than what we had expected. Physicians should consider SpA when they observe IBD patients with arthralgia, and refer them to an appropriate department if needed.

Transposition osteotomy of the acetabulum for advanced-stage osteoarthritis of the hips.

BACKGROUND: Transposition osteotomy of the acetabulum (TOA) was the first periacetabular osteotomy in which the acetabulum was transposed with articular cartilage. TOA improves coverage of the femoral head and joint congruity. The purpose of this study was to investigate whether TOA is an appropriate option for treating osteoarthritis of the hips at the advanced stage by comparing it with matched control hips at the early stage. METHODS: Between 1998 and 2001, TOA was performed in 104 hips of 98 patients. Altogether, 16 of 17 hips (94%) with osteoarthritis at the advanced stage were examined and compared with 37 matched control hips at the early stage. The mean age at the operation was 48 years (38-56 years), and the mean follow-up period was 88 months (65-107 months). RESULTS: TOA corrected the acetabular dysplasia and significantly improved containment of the femoral head. Clinical scores were also significantly improved in both groups. In the advanced osteoarthritis cases, there was a tendency for abduction congruity before transposition osteotomy of the acetabulum to reflect the clinical outcome. CONCLUSIONS: TOA is a promising treatment option for advanced osteoarthritis of the hips as well as for patients at an early stage when preoperative radiographs show good congruity or containment of the joint.

Vertebral strength changes in rheumatoid arthritis patients treated with alendronate, as assessed by finite element analysis of clinical computed tomography scans: a prospective randomized clinical trial.

OBJECTIVE: Finite element analysis of clinical computed tomography (CT) scans provides a noninvasive means of assessing vertebral strength that is superior to dual x-ray absorptiometry (DXA)-measured areal bone mineral density. The present study was undertaken to compare strength changes, measured using this newer method, in rheumatoid arthritis (RA) patients who were treated with alendronate (ALN) versus those who were not. METHODS: Thirty female RA patients without radiologic signs of L3 compression fractures or a history of osteoporosis medication were enrolled in a prospective randomized clinical trial. Patients were randomly assigned to the ALN group (5 mg orally, once daily) or the control group not receiving antiresorptive treatment. All patients were evaluated by DXA and quantitative CT at baseline and reevaluated after a mean of 12.2 months. Nonlinear finite element analysis was performed on the CT scans (n = 29 available for analysis) to compute an estimate of vertebral compressive strength and to assess strength changes associated with changes in the trabecular compartment and the outer 2 mm of bone (peripheral compartment). RESULTS: On average, vertebral strength was significantly decreased from baseline in the control group (n = 15) (median change -10.6%; P = 0.008) but was maintained in the ALN group (n = 14) (median change +0.4%; P = 0.55), with a significant difference between the 2 groups (P < 0.01). Strength decreased more rapidly within the trabecular bone, and ALN treatment was much more effective in the peripheral than the trabecular compartment. CONCLUSION: Our results indicate that patients with RA can lose a substantial amount of vertebral strength over a relatively short period of time, and this loss can be prevented by ALN, primarily via its positive effect on the outer 2 mm of vertebral bone.

Interleukin-15 selectively expands CD57+ CD28- CD4+ T cells, which are increased in active rheumatoid arthritis.

Proinflammatory cytokines as well as CD4(+) T cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recently, an increase of CD57(+) or CD28(-)CD4(+) T cells was demonstrated in RA, although the mechanism of the increase of these T cells is unclear. In this study, we first examined the relationship between CD57(+)CD4(+) T cells and CD28(-)CD4(+) T cells and found CD57(+)CD28(-)CD4(+) T cells, but neither CD57(+)CD28(+) nor CD57(-)CD28(+) cells, expanded in the peripheral blood of active RA. In vitro experiments revealed that CD57(+)CD28(-)CD4(+) T cells selectively expanded in response to IL-15. Furthermore IL-15-stimulated CD57(+)CD28(-)CD4(+) T cells induced TNF-alpha production from monocytes. These results suggest that CD57(+)CD28(-)CD4(+) T cells are involved in the pathogenesis of RA by responding to IL-15.

The accuracy of socket orientation using a pelvic fixation device for total hip arthroplasty with the patient in the lateral decubitus position in comparison to the vacuum bag fixation method.

BACKGROUND: In our department, a vacuum bag with two lateral boards used to be utilized in order to maintain patients in the lateral decubitus position during THA. However, we recently changed this modality to a three-point fixation device for the pelvis in order to accurately control the position of the acetabular socket. The purpose of this study was to retrospectively compare the orientation of the acetabular socket when THA was carried out using two different positioning methods. METHODS: Group 1 consisted of 66 hips that underwent THA in 1997 using a vacuum bag, which became rigid with suction. Group 2 consisted of 42 hips that were treated in 2000 using a three-point fixation device for the pelvis. This device was designed to able to rigidly fix the bilateral anterior superior iliac spines and the sacrum. Before fixation with the device, the angle between the line aligning the anterior-superior iliac spines and the vertical plane in the lateral decubitus position was measured as the lateral pelvic tilt. The orientation of the fixed acetabular socket was evaluated based on postoperative radiographs. RESULTS: The average absolute value from 45 degrees in the abduction angle was significantly lower in group 2 than that in group 1 (p < 0.01). In 18% of the cases in group 1, the anteversion angle was over 30 degrees. In contrast, no such cases were observed in group 2. Postoperative dislocation occurred in six cases (9%) in group 1. In contrast, it only occurred in one case (2%) in group 2. CONCLUSIONS: The positioning method using the pelvic fixation device enabled surgeons to more accurately control the position of the sockets during THA comparison to using the vacuum bag. The positioning of the patient is therefore suggested to be an important first step in successfully performing THA procedures.

Subchondral insufficiency fracture of the femoral head in younger adults.

We report two cases of subchondral insufficiency fracture of the femoral head observed in younger adults without any history of overexertion. In both cases, MRI revealed an irregular, discontinuous low-intensity band on the T1-weighted images. Both patients were treated operatively, and histological examination confirmed the diagnosis of subchondral fracture. A diagnosis of subchondral insufficiency fracture needs to be put in as one of the diagnoses in younger patients with a hip pain.

Outcome of the contralateral hip in rapidly destructive arthrosis after total hip arthroplasty: a preliminary report.

We investigated the outcome of the contralateral hip in patients with rapidly destructive arthrosis of the hip after total hip arthroplasty. Twenty-four patients were included, and the mean duration of radiographic follow-up was 7.0 years (range, 3.8-17.8 years). To assess the capable parameters for predicting the development of osteoarthritis, we evaluated the receiver operating characteristic curves. Three (12.5%) of 24 patients developed osteoarthritis and underwent total hip arthroplasty within 3.8 to 6.5 years. In these 3 patients, both the acetabular-head index and the center-edge angle were significantly lower than those in patients without osteoarthritis (P < .005). Based on the receiver operating characteristic curves, both an acetabular-head index of less than 72% and a center-edge angle of less than 16 degrees were considered to be associated with the development of osteoarthritis.

The protective effects of incadronate on inflammation and joint destruction in established rat adjuvant arthritis.

The effects of a new generation bisphosphonate, incadronate, in established adjuvant arthritis rats were evaluated according to the arthritis index, hind paw volume, and radiological and histopathological examinations. Incadronate suppressed the radiological and histopathological changes of hind paws, as well as the joint swelling in a dose-dependent manner. In contrast, the arthritis control rats showed drastic joint inflammation, marked destruction of bone and articular cartilage. The remains of articular cartilage lost Safranin O staining, and were attached with numerous TRAP-positive multinuclear cells. Some of resorption lacunas could be seen at the cartilage matrix nearby the TRAP-positive multinuclear cells. As regards the chondroprotective effects of bisphosphonates, we speculate that it is probably concerned with the inhibition of the chondroclasts. These data indicate that bisphosphonates may be a class of effective agent that can be considered for treatment of various arthritic conditions, including human rheumatoid arthritis.

Early MRI findings of the acetabulum and femoral head in a dysplastic hip resulting in a rapid destruction of the hip joint.

We documented a case of rapidly destructive arthrosis of the hip joint (RDA), in whom abnormal findings were observed not only in the femoral head but also in the acetabulum on magnetic resonance images (MRI) in the early stage. Radiographs made 1 month after the onset of pain showed a slight narrowing of the joint space. MRI obtained 2 months after the onset detected small foci of low signal intensity in the subchondral area of the femoral head on the T1-weighted images, and a linear pattern of high signal intensity in the lateral side of the acetabulum on the T2-weighted images. During the 17-month follow-up period, this case eventually underwent massive destruction of the femoral head as well as the acetabulum.

Bilateral subchondral insufficiency fracture of the femoral head after renal transplantation: a case report.

This report describes the case of a 47-year-old woman who was found to have subchondral insufficiency fractures in both femoral heads after renal transplantation. Initially, plain radiographs showed no obvious changes, but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low-intensity band on the T1-weighted image of both hips. The patient was treated nonsurgically. Ten months after onset, the pain in both hips disappeared, and plain radiographs and MRI showed no abnormalities. Subchondral insufficiency fracture should be considered in the diagnosis of patients who have hip pain after renal transplantation.

[Bone quantity and quality to its mechanical integrity].

Bone strength is made up of quantity (mass, mineralization), geometry (anatomy, micro architecture, collagen structure), and turnover/damage accumulation. While most of the mechanical behavior can be explained by measures of porosity, several additional descriptors of the geometry have been proposed for better predictions of fracture risk. This review introduces various aspects of these relationships between bone quantity and quality to its mechanical integrity.

Atlantoaxial instability in neck retraction and protrusion positions in patients with rheumatoid arthritis.

STUDY DESIGN: Radiographic analysis of the upper cervical spine was performed in patients with rheumatoid arthritis who had C1-C2 instability. OBJECTIVE: To assess whether neck retraction or neck protrusion movements can cause C1-C2 subluxation in patients with C1-C2 instability. SUMMARY OF BACKGROUND DATA: Cervical protrusion is the position where the head is maximally translated anteriorly with zero sagittal rotation, and this position has been shown to produce maximal C1-C2 extension. In contrast, cervical retraction is the position where the head is maximally translated posteriorly, and this position produces maximal C1-C2 flexion. To date, there have been no studies evaluating the effects of these two positions on C1-C2 status in patients with C1-C2 instability. METHODS: Twenty-four patients with rheumatoid arthritis who showed an atlantodental interval of at least 5 mm during neck flexion were evaluated in this study. These patients were instructed to actively hold the neck in protrusion and retraction positions, as well as in flexion and extension positions. Lateral cervical radiographs were taken to measure the C1-C2 angle and the atlantodental interval in the sagittal plane in each position. RESULTS: Retraction produced both maximal C1-C2 flexion and anterior C1-C2 subluxation, of a degree just the same as that produced by cervical flexion. Protrusion reversely produced maximal C1-C2 extension. However, 9 of 24 patients exhibited C1-C2 subluxation even in this protrusion position, in marked contrast to the cervical extension position in which only 2 of 24 patients showed C1-C2 subluxation. The patients who showed C1-C2 subluxation in the protrusion position tended to have more severe C1-C2 instability and less capacity for C1-C2 extension than the other patients who achieved a reduction of C1-C2 in the protrusion position. CONCLUSION: In patients with C1-C2 instability, not only cervical flexion but also cervical retraction constantly led to both maximal C1-C2 flexion and subluxation. In some patients with severe C1-C2 instability, protrusion also resulted in C1-C2 subluxation, even though the C1-C2 was maximally extended.

Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis.

OBJECTIVE: Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA). METHODS: Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed. CONCLUSION: Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.

Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints.

Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.

Involvement of CD4+,CD57+ T cells in the disease activity of rheumatoid arthritis.

OBJECTIVE: To evaluate the relationship between the frequency of peripheral CD57+ T cells and the physical status of rheumatoid arthritis (RA) patients, and to perform cytokine analysis of these CD57+ T cells. METHODS: Four-color fluorescence-activated cell sorter analysis was performed to detect both cell surface antigens and intracellular cytokines in peripheral blood leukocytes, using monoclonal antibodies against CD3, CD4, CD8, CD57, interferon-gamma (IFNgamma), and interleukin-4 (IL-4). RA patients were clinically evaluated with a modified Health Assessment Questionnaire (M-HAQ), joint score, face scale, and visual analog scale (VAS) assessing pain and disease activity. RESULTS: There was a significant correlation between the frequency of CD4+,CD57+ T cells and erythrocyte sedimentation rate (ESR), whereas a correlation was not found between the frequency of CD8+,CD57+ T cells and ESR. The frequency of CD4+,CD57+ T cells also showed a significant correlation with the mHAQ score, VAS, and face scale. Again, there was no significant correlation between the above-mentioned clinical scores and the frequency of CD8+,CD57+ T cells. Flow cytometric analysis of intracellular cytokines revealed that 14.5% of the CD57+ T cells produced IFNgamma, whereas only 2.8% of the CD57+ T cells produced IL-4 in RA patients. CONCLUSION: Evidence showing that the frequency of CD4+,CD57+ T cells among CD3+ cells of RA patients had a significant correlation not only with ESR but also with the physical status of the patients, and that a large proportion of the CD4+,CD57+ T cells had the capacity to produce IFNgamma, strongly suggests that these CD4+,CD57+ T cells are involved in the immunopathogenesis of RA.

Relationship between the maximum flexion-internal rotation test and the torn acetabular labrum of a dysplastic hip.

To determine the relationship between pain at flexion-rotation and the status of a labral tear in patients with dysplastic hips, physical examination maneuvers and hip arthroscopy were carried out in 59 patients with dysplastic osteoarthritis (5 men and 54 women; mean age, 41 years; range, 16 to 64 years). Between January 1998 and June 2000, these patients underwent 60 hip arthroscopies at Kyushu University Hospital. All hip joints arthroscoped demonstrated incomplete or complete detaching tears of the acetabular labrum in one portion of the weight-bearing area. Twenty-three patients (39%) experienced pain during the maximum flexion-internal rotation test; 16 patients (27%) showed a positive result for the maximum flexion-external rotation test. There was no statistically significant relationship between the results of the maximum flexion-external rotation test and the arthroscopic findings of labral tears. A positive maximum flexion-internal rotation test result, however, correlated well with incomplete detaching tears in the posterosuperior portion of the acetabular labrum. In contrast, a complete detaching tear of the posterosuperior labrum was associated with a negative maximum flexion-internal rotation test result. The maximum flexion-internal rotation test is useful for assessing the magnitude of a labral tear in the posterosuperior portion of the acetabular labrum in dysplastic hips.