中村 順一

OBJECTIVE: We aimed to determine the prevalence and risk factors for osteonecrosis of the femoral head (ONFH) in a multicentre cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: One hundred and eighty-six AAV patients who underwent radiographs and MRI screening of bilateral hip joints at more than 6 months after initial remission induction therapy (RIT) were retrospectively assessed for the presence of ONFH. RESULTS: Among 186 AAV patients, 33 (18%) were diagnosed with ONFH. Among the patients with ONFH, 55% were asymptomatic and 64% had bilateral ONFH. Seventy-six per cent of ONFH joints were in precollapse stages (stage ≤2), whereas 24% of ONFH joints were in collapse stages (stage ≥3). Moreover, 56% of the precollapse stage joints were already at risk of future collapse (type ≥C-1). Even in asymptomatic ONFH patients, 39% of the precollapse stage joints were type ≥C-1. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH in AAV patients (OR 1.072, 95% CI 1.017 to 1.130, p=0.009). Rituximab use was a significant beneficial factor against ONFH (p=0.019), but the multivariate analysis rejected its significance (p=0.257). CONCLUSION: Eighteen per cent of AAV patients developed ONFH, and two-thirds of the ONFH joints were already in collapse stages or at risk of future collapse. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH. A rapid reduction of glucocorticoids in RIT and early detection of precollapse ONFH by MRI may decrease and intervene ONFH development in AAV patients.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

BACKGROUND: Osteoarthritis (OA) is the most common disease of the hip in adults, and its etiology is divided into two groups: primary and secondary. Although acetabular dysplasia is the most frequent reason for total hip arthroplasty (THA) in Japan, primary OA has increased recently. Although there are two types of femoral head migration in primary OA: superior and medial, there are some patients with prominent femoral head lateralization. This study aimed at evaluating the relationship between femoral head lateralization and bone morphology of the acetabulum and proximal femur using radiographic factors in primary OA of the hip. METHODS: A retrospective study was conducted between 2008 and 2017 to assess 1308 hips with OA who underwent primary THAs at our institute. The diagnostic criteria for primary OA were Crowe type 1, Sharp's angle <45°, and center-edge (CE) angle >25°. We classified patients with primary OA into two groups based on femoral head lateralization: group L with lateralization or group N without. Radiographic factors included Sharp's angle, CE angle, acetabular inclination, acetabular depth ratio (ADR), acetabular head index (AHI), and femoral neck-shaft angle (FNA), all examined on an anteroposterior pelvic radiograph. Femoral neck anteversion was calculated using computerized axial tomography. RESULTS: Primary OA was diagnosed in 210/1308 hips (16.1%) (group L: 112 hips (8.6%); group N: 98 (7.5%)). Patient demographics were not significantly different. Radiographic factors with observed significant differences between group L and group N were the average CE angle (33.0° vs. 35.1°, respectively, p = 0.009), ADR (251.6 vs. 273.4, p < 0.001), AHI (77.2 vs. 80.4, p < 0.001), and FNA (136.9° vs. 134.8°, p = 0.012). CONCLUSIONS: This investigation suggests that primary OA with femoral head lateralization demonstrated specific identifiable radiographic characteristics in the acetabulum and proximal femur that might contribute to hip joint instability such as the dysplastic hip.

Abstract Objectives Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA). However, the precise mechanisms by which MTX stalls RA progression and alleviates the ensuing disease effects remain unknown. The aim of the present study was to identify novel therapeutic target molecules, the expression patterns of which are affected by MTX in patients with RA. Methods CD4⁺ T cells from 28 treatment-naïve patients with RA before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression levels of semaphorin 3G, a differentially expressed gene, and its receptor, neuropilin-2, were evaluated in the RA synovium and collagen-induced arthritis synovium. Collagen-induced arthritis and collagen antibody-induced arthritis were induced in semaphorin3G-deficient mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of semaphorin 3G-stimulated bone marrow-derived macrophages were analyzed in vitro. The effect of local semaphorin 3G administration on the clinical score and number of infiltrating macrophages during collagen antibody-induced arthritis was evaluated. Results Semaphorin 3G expression in CD4⁺ T cells was downregulated by MTX treatment in RA patients. It was determined that semaphorin 3G is expressed in RA but not in the osteoarthritis synovium; its receptor neuropilin-2 is primarily expressed on activated macrophages. Semaphorin3G deficiency ameliorated collagen-induced arthritis and collagen antibody-induced arthritis. Semaphorin 3G stimulation enhanced the migration and proliferation of bone marrow-derived macrophages. Local administration of semaphorin 3G deteriorated collagen antibody-induced arthritis and increased the number of infiltrating macrophages. Conclusions Upregulation of semaphorin 3G in the RA synovium is a novel mechanism that exacerbates joint inflammation, leading to further deterioration, through macrophage accumulation.

BACKGROUND: Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). METHODS: We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. RESULTS: Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. CONCLUSION: DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.

PURPOSES: To analyze T2 relaxation times of the facet joint by MRI T2-mapping in patients with degenerative lumbar disorders (DLD), and to determine the correlation with lumbar instability in radiographs. METHODS: We conducted a T2-mapping of the lumbar facet joint using a 1.5 T MRI system. We classified patients with degenerative lumbar disorders scheduled to undergo decompression surgery into groups with stability and instability using radiographs, and compared the T2 relaxation times of the lumbar facet. Lumbar instability was defined as the presence of anterior translation ratio > 5% or disk range of motion (ROM) > 5° in the sagittal plane of SLFE radiographs. RESULTS: Inclusion criteria were met by 22 patients (45 levels, mean age 64.3 years). Facet effusions had high sensitivity (90%) but had low specificity (28%) for diagnosis of lumbar instability. Mean T2 relaxation times of right and left facet joints are significantly longer (98.4 ms) in the instability group than they are (87.6 ms) in the stability group (p < 0.001). Anterior translation ratio was positively correlated with mean T2 relaxation times of facet joint (R2 = 0.493, p < 0.05). From a ROC analysis, the cutoff value of T2 relaxation times for lumbar instability was 98.65 ms (sensitivity 60.0%, specificity 95.7%, AUC 0.763). CONCLUSIONS: The T2 relaxation times were positively correlated with lumbar instability. This new quantitative evaluation of lumbar facet joint using MRI T2-mapping might be useful to determine lumbar instability.

BACKGROUND: Monoiodoacetate (MIA)-induced arthritis models are used widely in osteoarthritis (OA) research to develop effective conservative treatments for hip OA, as an alternative to joint replacement surgery. In joint OA models, such as the MIA-induced knee OA model, various doses of MIA are utilized, depending on the purpose of the research. So far, only 2 mg of MIA has been used for MIA-induced hip OA research. We hypothesized that the amount of MIA should be adjusted according to the osteoarthritis model under investigation. We performed radiographic and histological evaluations in rats for hip OA models induced by different doses of MIA. METHODS: One hundred and eighty right hips of six-week-old, male Sprague-Dawley rats (n = 30 rats per group) were treated with either a single intra-articular injection of various doses of MIA (0.25, 0.5, 1.0, 2.0, and 4.0 mg) dissolved in 25 μl of sterile saline (MIA group), or with 25 μl of sterile saline alone (Sham group). Radiographic and histological evaluations of the hip joint were performed at one, two, four, eight, and 12 weeks after administration (n = 6 rats per group per time point). RESULTS: OA changes progressed from 1 week after administration in the 1.0-mg, 2.0-mg, and 4.0-mg MIA groups. The degree of OA changes increased as the dose of MIA increased. The 0.25-mg and 0.5-mg MIA groups presented fewer OA changes than the 2.0-mg and 4.0-mg MIA groups during the entire study period (up to 12 weeks). The administration of 0.25 mg and 0.5 mg of MIA-induced both radiographic and histological OA changes in a time-dependent manner, whereas more than 2 mg of MIA provoked end-stage OA at 8 weeks after injection. Absolute, dose-dependent histopathological OA changes were observed 4 weeks after MIA administration. CONCLUSIONS: Intra-articular MIA injection to the hip joints of rats induced diverse OA changes dose-dependently. Research for developing novel conservative treatments for hip OA and intractable pain should consider the pathological condition when determining the dose of MIA to be employed.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

ラット脊椎固定術モデルを用いて、ロモソズマブによる骨癒合促進および骨強度上昇効果について検討した。対象は、8週目齢のSprague-Dawley雄ラット12匹とした。第10胸椎～第2腰椎までの棘突起から骨移植骨として採取し、左右両側の椎間関節部から横突起までの間に置き、自家骨移植とした。体格差を徐すため、体重を基準にロモソズマブ群(R群)6匹と、Control群(C群)6匹に分類した。R群にはロモソズマブ、C群には生理食塩水を25mg/kg、10週間、毎週2回皮下注射を投与した。術直後と術後10週目にCT装置撮影を行い、両群における椎間関節および横突起間の骨癒合率と骨癒合部の体積を比較検討した。さらに、大腿骨の骨密度の計測と、腰椎後側方固定術を施行した脊椎背側の圧縮強度を評価した。その結果、平均骨癒合率はC群に対し、R群が有意に高かった。骨癒合部の体積は、術後直後は両群間で有意差はなかったが、術後8週目では、R群が有意に大きかった。平均骨密度については、R群が有意に大きかった。脊椎背側の平均圧縮強度は、R群が有意に高かった。破断後のCTで、骨折部位は全例で、椎体軟骨の終板上に認められた。

Introduction We compared preoperative skeletal muscle, pre-and post-operative spinal alignment or clinical symptoms between tandem spinal stenosis (TSS) patients who underwent simultaneous cervical and lumbar decompression and lumbar spinal stenosis (LSS) patients who underwent only lumbar decompression and the efficacy of one-stage surgery was examined. Methods This study included 82 patients, identifying 13 patients for the TSS group (mean age 77.2 years) and 69 patients for the LSS group (mean age 72.2 years). One-stage decompression surgery was performed on both groups. The spinal alignments were evaluated using Lumbar scoliosis (LS), Sagittal vertical axis (SVA), Lumbar lordosis (LL), Pelvic tilt (PT), Pelvic incidence (PI), and Sacral slope (SS). The clinical symptoms were evaluated using the visual analogue scale (VAS) score for low back pain (LBP), the Japanese Orthopedic Association scoring system (JOA score), the Roland-Morris Disability Questionnaire (RDQ), the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and Oswestry Disability Index (ODI). Results The amount of bleeding was not significantly different between the two groups (p > .05). SVA, LL, PT, and SS were significantly improved in the LSS group (p < 0.05). In the TSS group, SVA, LL, PT, and SS tended to improve, but without significant differences. The proportion of JOABPEQ gait dysfunction that was difficult to climb stairs was 83% in the TSS group, and social life disturbance that was difficult to engage in ordinary activities was 67% in the TSS group, which was significantly higher than that in the LSS group (p < .05). Although clinical symptoms improved by surgery in both groups (p < .05), there was no significant difference in the degree of clinical symptom improvement before and after surgery (p > .05). Conclusions One-stage surgery for TSS is effective because it has the same intraoperative bleeding volume as LSS alone and is minimally invasive. It also improves forward-leaning posture and clinical symptoms equivalent to LSS alone.

PURPOSE: We investigated changes in skeletal muscle mass and bone mineral density in degenerative lumbar scoliosis (DLS) patients during a 2-year follow-up following diagnosis. METHOD: This study included 418 Japanese women, identifying 50 patients for the DLS group (mean age 76.4 years) and 368 patients for the control group (mean age 73.4 years). Whole-body skeletal muscle mass was measured using a Bioelectrical Impedance Analyzer. Bone mineral density (BMD) was measured using DXA. Skin autofluorescence (SAF), a marker of advanced glycation end products in the skin, was measured using a spectroscope. Spinal alignment, skeletal muscle mass, BMD, grip strength, and SAF were examined and the amount of change 1 and 2 years from the initial examination for each item was compared between groups. RESULTS: Height, body fat mass, grip strength, upper limb muscle mass, and trunk muscle mass in the DLS group were significantly lower, and lumbar spine BMD was significantly greater compared to controls at the first visit (p < 0.05). There was no significant difference in spinal alignment in the DLS group after 2 years compared with baseline. Trunk muscle mass also decreased significantly more in the DLS group (-2.7%) than in the control group (-1.1%) over the 2-year follow-up (p < 0.05). DISCUSSION: In this study, trunk muscle mass in the DLS group decreased about 2.4 times more in 2 years compared with the control group (p < 0.05). It may be possible to clarify the mechanism of kyphoscoliosis progression in the future with large-scale longitudinal studies.

BACKGROUND: Proximal femur fractures are usually categorized as either a cervical or trochanteric fracture, but the relationship between fracture type and fall direction is not clear. By cadaveric mechanical testing and finite element analysis (FEA), the aims of this research were to verify the factors that define the proximal femur fracture type and to clarify the change in stress distribution based on fall direction. METHODS: From fresh frozen cadavers, we obtained 26 proximal femora including ten pairs of 20 femora. We conducted quasi-static compression tests in two fall patterns (lateral and posterolateral), and identified the fracture type. We then examined the relationship between fracture type and the following explanatory variables: age, sex, neck shaft angle, femoral neck length, bone mineral density (cervical and trochanteric), and fall direction. In addition, for the ten pairs of femurs, the effect of fall direction on fracture type was examined by comparing the left and right sides. In addition, we generated the proximal femur finite element (FE) models from computed tomography data to simulate and verify the change of external force in different fall directions. RESULTS: In mechanical tests, only fall direction was found to have a significant relationship with fracture type (p = 0.0227). The posterolateral fall group had a significantly higher incidence of trochanteric fractures than lateral fall group (p = 0.0325). According to FEA, the equivalent stress in the lateral fall was found to be more concentrated in the cervical area than in the posterolateral fall. CONCLUSION: In proximal femur fractures, fall direction was significantly associated with fracture type; in particular, trochanteric fractures were more likely to occur following a posterolateral fall than a lateral fall.

INTRODUCTION: Cemented femoral component design including its mechanical behavior in total hip arthroplasty (THA) has influenced the occurrence of postoperative periprosthetic femoral fracture (PPFF). The main aim of this study was to investigate the influence of the calcar collar and surface finish in the cemented femoral component on the risk of PPFF. MATERIALS AND METHODS: This retrospective review was undertaken of 1082 primary THAs in 912 patients using cemented femoral components followed for a minimum of five years (mean, 9.4 years; range, 5-24 years). The incidence of PPFF, patients' demographics and surgical details were evaluated. Kaplan-Meier survivorship analysis was performed for four different outcomes: any PPFF, revision of the femoral component for PPFF, aseptic loosening, and for any reason. RESULTS: The overall incidence of PPFFs was 1.0% (n = 11): 1.4% (n = 10) in the collarless polished (CLP) group, none in the collared polished (CP) group and 0.6% (n = 1) in the collared non-polished (CNP) group (p > 0.05). Kaplan-Meier survival analysis for the femoral component at 12 years with PPFF as the end point was 97.4% (95% confidence interval [CI], 94.9 to 99.8) in the collarless group and 99.7% (95% CI, 99.1 to 100) in the collared group (p = 0.048). With revision of the femoral component for aseptic loosening as the end point, survivorship was 100.0% in the CLP and CP groups, and 98.1% (95% CI, 95.9 to 100) in the CNP group (CLP vs CP, p > 0.999; CLP vs CNP, p = 0.001; CP vs CNP, p = 0.112). CONCLUSION: This study demonstrated that the calcar collar in the cemented femoral component could play an important role to reduce the incidence of PPFF. The surface finish in the cemented femoral components influenced the incidence of femoral component revision for aseptic loosening over 5-12 years. Surgeons should consider not only the geometry and the mechanical function of the femoral components based on different design philosophies, but also potential complications associated with different designs that may require revision arthroplasty.

BACKGROUND: The preservation of soft tissues is an important factor for preventing dislocation after total hip arthroplasty. Anatomical studies have revealed that the inferior iliofemoral ligament (ILFL) contributes significantly to the native stability of the hip. This study aimed to investigate the anatomical structures of the iliocapsularis muscle (ICM) and ILFL from a surgical perspective. METHODS: In total, we assessed 50 hip specimens from 25 embalmed cadavers. The size and location of ICM and ILFL (at the upper, middle, and lower parts of the femoral head) were assessed in a neutral position. The ratio of ICM and ILFL widths to the femoral head was evaluated. RESULTS: The mean ICM and ILFL widths were 7.5 and 14.6, 12.0 and 14.2, and 12.8 and 15.2 mm at the upper, middle, and lower levels, respectively. The mean ICM thicknesses were 1.3, 9.0, and 9.1 mm at the upper, middle, and lower levels, respectively. The distributions of ICM and ILFL from the lateral edge of the femoral head were 21.1%-37.4% and 4.9%-36.5%, 9.5%-35.6% and 7.9%-38.7%, and 11.0%-38.7% and 9.5%-42.4% at the upper, middle, and lower levels, respectively. CONCLUSION: ICM and ILFL were located at the anterolateral side of the femoral head, and the medial edge of the ILFL corresponded to that of the ICM. ICM can serve as a landmark for preserving ILFL in total hip arthroplasty using the anterior approach.

OBJECTIVE: To compare the effects of 3 implant designs, with and without hydroxyapatite reinforcement, on push/pull-out strength and rotational torque. METHODS: Three implant designs (Gamma 3, INTERTAN, and PFNA-II) were selected for comparison. A hydroxyapatite cylinder (NEOBRACE) was used to reinforce the interface between the femoral head and the lag screw. Maximum push-out strength, maximum pull-out strength, and peak rotational torque were measured in cellular blocks mimicking osteoporotic cancellous bone, with and without NEOBRACE. RESULTS: In the push-out test, INTERTAN produced a significantly higher push-out strength in osteoporotic bone density cellular blocks than the other lag screws and blades (P < .05). With the addition of NEOBRACE, push-out strength was significantly higher for INTERTAN and PFNA-II (P < .05) than for the non-NEOBRACE group. In the pull-out test, INTERTAN produced a significantly higher pull-out strength in the osteoporotic bone density cellular blocks than did the other lag screws and blades (P < .05). With the addition of NEOBRACE, the pull-out strengths of INTERTAN and Gamma 3 versus those of the non-NEOBRACE group significantly increased (P < .05). In the rotational torque test, INTERTAN produced significantly greater rotational torque in the osteoporotic cellular blocks than the other lag screws and blades (P < .05). The addition of NEOBRACE resulted in a significant increase in rotational torque only for INTERTAN (P < .05). CONCLUSION: The use of NEOBRACE supported an increase in push/pull-out strength and rotational torque, especially in systems with a relatively increased bone or implant interface area.Level of Evidence: Level V.

<title>Abstract</title> <sec> <title>Introduction</title> Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. </sec> <sec> <title>Methods</title> We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in-silico analyses. </sec> <sec> <title>Results</title> The Japanese GWAS identified four significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 (OR = 1.99, P-value = 1.1 × 10−9), TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10−8) and MYO16 (OR = 3.91, P-value = 4.9 × 10−10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. </sec> <sec> <title>Conclusions</title> We identified three novel susceptibility loci for S-ONFH in SLE. </sec>

OBJECTIVES: The pain of hip osteoarthritis (OA) is generally recognized as nociceptive in origin because of the local pathology. However, some patients with OA experience a neuropathic pain component as an essential part of some nociplastic pain subtype. Here, we sought to examine the mechanism of chronic pain of symptomatic hip OA by the association of its distribution, complex pain mechanism screening, and the prevalence of lumbar spinal stenosis. MATERIALS AND METHODS: We conducted a prospective cross-sectional study of 100 hips in 100 patients with symptomatic hip OA in a chronic state. We examined all baseline clinical characteristics including clinical and functional score, location of pain and numbness, and pain score (PainDETECT questionnaire and the Leeds Assessment of Neuropathic Symptoms and Signs), and magnetic resonance imaging of the hip and lumbar spine. RESULTS: The PainDETECT questionnaire and Leeds Assessment of Neuropathic Symptoms and Signs revealed that 23% of the patients had a neuropathic pain component. There were 24 variations of the pain pattern. By contrast, the pain localized around the hip joint was only 15%. Pain distal to the thigh and any numbness was significantly more frequent in the group with neuropathic pain (P<0.001). Lumbar spinal stenosis grade was not significantly different between patients with nociceptive pain and those with neuropathic pain. Pain score was significantly correlated with the pain in clinical and functional scores. DISCUSSION: Among patients with symptomatic hip OA, the distribution of pain was various, and about 23% of patients had neuropathic, nociplastic, or mixed pain as a possibility for somatosensory system disturbances.

We investigated the analgesic effects of tramadol and the arthritic changes following tramadol administration in the rat hip osteoarthritis (OA) model using mono-iodoacetate (MIA). The right hip joints of male Sprague-Dawley rats (n = 5 rats/group) in the Sham group were injected with 25 μl of sterile saline and 1% of fluorogold (FG) retrograde neurotracer. In the MIA + Vehicle and MIA + Tramadol groups, FG and 25 μl of sterile saline with 0.5 mg of MIA were injected into the right hip joint. The MIA + Vehicle and MIA + Tramadol groups were administered daily for 4 weeks, either sterile saline (10 mg/kg, intraperitoneal [i.p.]) or tramadol (10 mg/kg, i.p.). We assessed hyperalgesia every week after MIA administration. Histopathological changes and immunoreactive neurons for calcitonin gene-related peptide (CGRP) in dorsal root ganglia (DRG) were evaluated after 4 weeks of treatment. MIA injection into the hip joint led to mechanical hyperalgesia (p < 0.01), which was significantly reduced by tramadol administration (p < 0.01). Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001). MIA + Vehicle and MIA + Tramadol groups showed significant cartilage reduction and degeneration compared to the Sham group (p < 0.0001). Interestingly, OA changes significantly progressed in the MIA + Tramadol group compared to the MIA + Vehicle group (p < 0.0001).

PURPOSE: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. MATERIALS AND METHODS: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1-2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5-7 months after the administration of romosozumab. RESULTS: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1-2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5-7 months after romosozumab administration; and a significant increase only observed in the lumbar spine. CONCLUSION: Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.

Study Design: Prospective cohort study (open-label, single-arm, and non-blinded). Purpose: This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. Overview of Literature: IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. Methods: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months' chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions: Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1-4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Study Design: Retrospective observational study. Purpose: We investigated the correlation between T2 relaxation times and clinical symptoms in patients with cervical radiculopathy caused by cervical disk herniation. Overview of Literature: There are currently no imaging modalities that can assess the affected cervical nerve roots quantitatively. Methods: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. Results: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. Conclusions: In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.