Relationship between medial partite hallux sesamoid and hallux valgus in the general population.

BACKGROUND: An association between the medial partite hallux sesamoid (MPHS) and hallux valgus (HV) has been suggested; however, a causal relationship has not been confirmed. This study aimed to determine their causal relationship using a cross-sectional radiographic survey of a large-scale population cohort covering a wide age group. PATIENTS AND METHODS: The fifth survey of the Research on Osteoarthritis/Osteoporosis against Disability study involved 1997 participants aged 21-95 years who had undergone anteroposterior radiography of bilateral feet. The presence of MPHS, its morphology, and radiographic parameters related to the HV were assessed using radiographs. Changes in the prevalence of MPHS with age were assessed using trend tests. The relationship between the MPHS and HV was assessed based on sex and age. RESULTS: MPHS was found in 508 out of 3994 feet (12.7 %), with a significant difference in prevalence between men and women (10.0 % vs. 13.7 %, p < 0.001). Trend analysis demonstrated a significant decrease in MPHS occurrence with age in both sexes. HV angle was significantly higher in feet with MPHS than in those without (Men: 17.8 ± 7.0° vs. 14.0 ± 5.9°, p < 0.0001; Women: 19.6 ± 7.7° vs. 17.7 ± 7.9°, p < 0.0001). The prevalence of HV angle ≥ 20° was also significantly higher in feet with MPHS than in those without (Men: 33.3 % vs. 14.6 %, p < 0.0001; Women: 46.5 % vs. 34.6 %, p < 0.0001). This association between MPHS and HV was noticeable in younger adults and became less prominent with age. CONCLUSIONS: MPHS is associated with HV. The weakening of this relationship and the decreased prevalence of MPHS with age suggest that MPHS is not caused by HV, but is one of the causes of HV, especially in younger adults.

Trends in the prevalence of atrophic gastritis and Helicobacter pylori infection over a 10­year period in Japan: The ROAD study 2005­2015.

Few large population-based studies have examined the prevalence of atrophic gastritis (AG) and Helicobacter pylori infection in Japan. The purpose of the present study was to estimate the prevalence of AG and H. pylori infection by age, in addition to investigating their change rates from 2005 to 2016 in Japan using data from a large population-based cohort. A total of 3,596 participants [1,690 in the baseline survey (2005-2006) and 1,906 at the fourth survey (2015-2016)] aged 18 to 97 years were included in the cohort. The prevalence of AG and H. pylori infection were examined at baseline and in the fourth survey based on serological tests for the H. pylori antibody titer and pepsinogen levels. The prevalence of AG and H. pylori infection were 40.1% (men, 44.1%; women, 38.0%) and 52.2% (men, 54.8%; women, 50.8%), respectively, at baseline. AG seropositivity rates showed a significant decrease from 40.1 to 25.8% in 10 years. H. pylori seropositivity rates decreased significantly from 52.2 to 35.5% in 10 years. Stratified for age, the prevalence of AG showed an increasing trend with age, whereas the prevalence of H. pylori infection increased with aging, except for in the elderly group, showing an inverted U-shaped association. In this population-based, cross-sectional study with a 10-year interval survey, the prevalence of AG and H. pylori infection decreased significantly. This change may influence the prevalence of H. pylori-related diseases, including extra-gastric disorders associated with H. pylori-induced systemic subclinical inflammation and hypochlorhydria, such as colorectal neoplasia and arteriosclerosis.

Involvement of orthopaedic surgeons for cancer patients in orthopaedic training facilities certified by the Japanese Orthopaedic Association - A nationwide survey.

BACKGROUND: In order to improve cancer care in Japan further, it is now required for orthopaedic surgeons to get actively involved in managing locomotive organs such as bones, muscles and nerves in cancer patients. In 2018, the Japanese Orthopaedic Association (JOA) conducted a questionnaire survey to investigate the current status of cancer treatment at the orthopaedic training facilities certified by the JOA. We analyzed the results of that questionnaire survey, focusing on the data from the core hospitals for cancer care (designated cancer hospitals), to clarify the involvement of orthopaedic surgeons in cancer treatment. MATERIALS AND METHODS: A nationwide survey was conducted in the orthopaedic training facilities certified by the JOA using an online questionnaire from March 15th to 31st, 2018. To clarify the involvement of orthopaedic surgeons in cancer treatment, we analyzed the results of that questionnaire survey, focusing on the data from the designated cancer hospitals in Japan. RESULTS: From the questionnaire survey, it became clear that 24% of the orthopaedic training facilities certified by the JOA are designated cancer hospitals. There were significant differences concerning cancer treatment and the prospect of orthopaedic surgeons' involvement in the treatment for bone metastases between institutions classified according to number of both certified orthopaedic surgeons by the JOA and specialists for bone and soft tissue tumors. In addition, in 45% of the designated cancer hospitals, orthopaedic surgeons treated bone metastases that occur in cancer patients, but in the rest of the institutions, orthopaedic surgeons did not yet adequately respond. CONCLUSION: In order to further improve the locomotive function and quality of life (QOL) in cancer patients, it was seemed to be necessary that all medical professionals engaged in cancer treatment, including orthopaedic surgeons, recognize the importance of locomotive management for cancer patients. In addition, the results of this study suggested that the presence of more than six certified orthopaedic surgeons by the JOA, including one or more specialists for bone and soft tissue tumors, may be able to create an environment conducive to the involvement of orthopaedic surgeons in cancer treatment at the facility.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

Practical guidance to handle missing values in the 25-question Geriatric Locomotive Function Scale (GLFS-25): a simulation study.

OBJECTIVES: Despite the possible large number of missing values on the 25-question Geriatric Locomotive Function Scale (GLFS-25), how we should treat them is unknown. In a simulation study, we investigated how to handle missing values in the GLFS-25. DESIGN, SETTING AND PARTICIPANTS: We used three datasets with different participant characteristics: community dwellers who could walk by themselves, outpatients of orthopaedics owing to pain, and patients who required surgery for total knee replacement or lumbar spinal canal stenosis. OUTCOME MEASURES: The missing items of the datasets were artificially created, and four statistical methods, complete case analysis, multiple imputation, single imputation using individual mean, and single imputation using individual domain average, were compared in terms of bias and mean squared error. Simulation studies were conducted to compare them under varying numbers of participants with missing values (5%-40%) and under varying numbers of missing items of GLFS-25 (4-16). RESULTS: Multiple imputation had the lowest root mean squared error. Complete case analysis showed the largest bias, and the performances of the single imputation were between those methods. The relative performances were similar across the three datasets. The absolute bias of the single imputation was<0.1. The bias and mean squared error of multiple imputation and single imputation were comparable when the number of missing items was less than or equal to eight. CONCLUSIONS: Multiple imputation is preferable, although single imputation using subject average/subject domain average can be used with practically negligible bias as long as the number of missing items is up to 8 out of 25 items in each individual of the population.

Association between acetabular dysplasia and sagittal spino-pelvic alignment in a population-based cohort in Japan.

The relationship between acetabular dysplasia and spino-pelvic alignment remains unclear. The aim of this study was to clarify the association between acetabular dysplasia and spino-pelvic alignment, based on a large-scale population-based cohort in Japan. From the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, 1,481 participants (491 men and 990 women; mean age, 65.3 years) were analyzed. Center-edge (CE) angle and spino-pelvic parameters (lumbar lordosis, LL; sacral slope, SS; pelvic tilt, PT; pelvic incidence, PI) were measured radiographically. Acetabular dysplasia was defined as a CE angle < 20°, and associations between acetabular dysplasia and spino-pelvic parameters were assessed. The group with acetabular dysplasia had significantly higher age, higher percentage of female, higher SS and higher PI than the group without acetabular dysplasia in a univariate analysis. On the other hand, acetabular dysplasia was not significantly associated with spino-pelvic parameters in a multiple logistic regression analysis that include age, sex, SS and PI as explanatory variables; however, PI demonstrated a positive odds ratio (odds ratio, 1.02; 95% CI 1.00-1.04). In conclusion, acetabular dysplasia was not significantly associated with spino-pelvic parameters, but higher PI may be an associated factor for acetabular dysplasia.

Is radiographic lumbar spinal stenosis associated with the quality of life?: The Wakayama Spine Study.

OBJECTIVES: This prospective study aimed to determine the association between radiographic lumbar spinal stenosis (LSS) and the quality of life (QOL) in the general Japanese population. METHODS: The severity of radiographic LSS was qualitatively graded on axial magnetic resonance images as follows: no stenosis, mild stenosis with ≤1/3 narrowing, moderate stenosis with a narrowing between 1/3 and 2/3, and severe stenosis with > 2/3 narrowing. Patients less than 40 years of age and those who had undergone previous lumbar spine surgery were excluded from the study. The Oswestry Disability Index (ODI), which includes 10 sections, was used to assess the QOL. One-way analysis of variance was performed to determine the statistical relationship between radiographic LSS and ODI. Further, logistic regression analysis adjusted for gender, age, and body mass index was performed to detect the relationship. RESULTS: Complete data were available for 907 patients (300 men and 607 women; mean age, 67.3±12.4 years). The prevalence of severe, moderate, and non-mild/non-radiographic were 30%, 48%, and 22%, respectively. In addition, the mean values of ODI in each group were 12.9%, 13.1%, and 11.7%, respectively, and there was no statistically significant difference between the three groups in logistic analysis (P = 0.55). In addition, no significant differences in any section of the ODI were observed among the groups. However, severe radiographic LSS was associated with low back pain in the "severe" group as determined by logistic analysis adjusted for gender, age, and body mass index (odds ratio: 1.53, confidence interval: 1.13-2.07) compared with the non-severe group. CONCLUSION: In this general population study, severe radiographic LSS was associated with low back pain (LBP), but did not affect ODI.

The prevalence of tandem spinal stenosis and its characteristics in a population-based MRI study: The Wakayama Spine Study.

PURPOSE: Tandem spinal stenosis (TSS) is a condition of combined spinal stenosis in the cervical and lumbar regions. The purpose of this study was to determine the prevalence of radiographic TSS and its association with developmental canal stenosis (DCS). The second purpose was to investigate the extent to which radiographic TSS is associated with cervical myelopathy and symptomatic LSS. METHODS: We recruited 1011 (336 men and 675 women) participants in this population-based study. After excluding those with a pacemaker, a history of cervical or lumbar surgery, disqualification, the MRI data of whole spine was analysed in 931 (mean, 67.3 years) participants. Cervical cord compression (CCC) and radiographic lumbar spinal stenosis (LSS) were evaluated by MRI. The canal-to-body ratio was also measured by plain X-ray. DCS was diagnosed as canal-to-body ratio <0.75. The diagnosis of cervical myelopathy and symptomatic LSS was made by presentation of both symptoms and radiographic compression using MRI. RESULTS: The prevalence of CCC was 24.7%, that of radiographic LSS was 30.2%, and that of radiographic TSS was 11.0% (men, 14.1%; women, 9.4%). The prevalence of TSS was significantly higher in the DCS group than in the non-DCS group (p < 0.001). Among the participants with radiographic TSS, the prevalence of cervical myelopathy and symptomatic LSS was 9.8 and 18.6%, respectively. The coexisting cervical myelopathy and symptomatic LSS was 6.1% in the participants with LSS. CONCLUSIONS: The present study is the first population-based study to clarify TSS characteristic using whole-spine MRI.

Psychometric Assessment of the Japanese Version of the Zurich Claudication Questionnaire (ZCQ): Reliability and Validity.

PURPOSE: The Zurich Claudication Questionnaire (ZCQ) is a self-administered measure to evaluate symptom severity, physical function, and surgery satisfaction in lumbar spinal stenosis (LSS). The purpose of this study is to assess the psychometric properties of the Japanese ZCQ in LSS patients. METHODS: LSS patients who are scheduled to undergo surgery were recruited from 12 facilities. Responses to several questionnaires, including the Japanese ZCQ; the visual analogue scale (VAS) to evaluate the degree of pain in the buttocks/legs, numbness in the buttocks/legs, and low back pain; the Oswestry Disability Index (ODI); and the SF-36v2, were collected before surgery and again 3 months after surgery (the post-surgery ZCQ was administered twice for test-retest reliability). For reliability, test-retest reliability was evaluated using the intra-class coefficient (ICC) and internal consistency was evaluated using Cronbach's alpha coefficient. Concurrent validity was assessed using Spearman's correlation coefficients between the Japanese ZCQ and other questionnaires. Effect size (ES) and standard response mean were calculated for responsiveness. All analyses were performed individually for the Japanese ZCQ symptom, function, and satisfaction domains. RESULTS: Data from 180 LSS patients were used in this analysis. The ICCs were 0.81, 0.89, and 0.88 and Cronbach's alpha coefficients were 0.78, 0.84, and 0.92 for the Japanese ZCQ symptom, function, and satisfaction domains, respectively. Regarding the concurrent validity, strong correlations (±0.5) were demonstrated between the Japanese ZCQ domains and the VAS leg pain, ODI, and SF-36v2 physical functioning or bodily pain, whereas correlations were approximately 0.3 in scales measuring other symptoms that are less related to symptom, function, or satisfaction domains. ESs showed high values for the ZCQ symptom and function domains (-1.73 for both). CONCLUSIONS: These psychometric assessments demonstrate that the Japanese ZCQ is a psychometrically reliable and valid measure in LSS. The Japanese ZCQ can evaluate both multi-dimensional aspects and the level of surgery satisfaction.

Development of a screening program to assess motor function in the adult population: a cross-sectional observational study.

BACKGROUND: Motor dysfunction is a major reason why the elderly lose their independence in their daily lives. The concept of locomotive syndrome has been proposed to describe the risk of mobility dependence caused by various locomotive organ disorders. The preservation of locomotive organs is now socially important in the middle-aged and geriatric population. Therefore, it is important to establish a screening program to evaluate motor function and related quality of life in a wide range of ages. METHODS: We propose a new set of pre-existing scales (the Two-Step test, Stand-Up test, and 25-question Geriatric Locomotive Function Scale) as screening tools to identify the population at high risk for locomotive syndrome. We performed a preliminary survey on 777 subjects who had no apparent disorders related to motor function. We also examined the reliability of the Two-Step test and Stand-Up test. RESULTS: We found that each scale did not show ceiling or floor effects in various age groups. Because the correlations between the three scales were significant but weak, we assume that each scale covers different aspects of mobility. The test-retest reliability was found to be satisfactory for the Two-Step test and the Stand-Up test. CONCLUSION: Our results suggest that our "Short Test Battery for Locomotive syndrome" is a feasible and reliable tool for screening the adult population as a preventative strategy for locomotive syndrome in a super-aged society.

Prevalence of diffuse idiopathic skeletal hyperostosis (DISH) of the whole spine and its association with lumbar spondylosis and knee osteoarthritis: the ROAD study.

We aimed to assess the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) and its association with lumbar spondylosis (LS) and knee osteoarthritis (KOA) using a population-based cohort study entitled Research on Osteoarthritis/osteoporosis Against Disability (ROAD). In the baseline ROAD study, which was performed between 2005 and 2007, 1,690 participants in mountainous and coastal areas underwent anthropometric measurements and radiographic examinations of the whole spine (cervical, thoracic, and lumbar) and both knees. They also completed an interviewer-administered questionnaire. Presence of DISH was diagnosed according to Resnick criteria, and LS and KOA were defined as Kellgren-Lawrence (KL) grade ≥3. Among the 1,690 participants, whole-spine radiographs of 1,647 individuals (97.5%; 573 men, 1,074 women; mean age, 65.3 years) were evaluated. Prevalence of DISH was 10.8% (men 22.0%, women 4.8%), and was significantly higher in older participants (presence of DISH 72.3 years, absence of DISH 64.4 years) and mainly distributed at the thoracic spine (88.7%). Logistic regression analysis revealed that presence of DISH was significantly associated with older age [+1 year, odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03-1.14], male sex (OR: 5.55, 95% CI: 3.57-8.63), higher body mass index (+1 kg/m(2), OR: 1.08, 95% CI: 1.02-1.14), presence of LS (KL2 vs KL0: 1, OR: 5.50, 95% CI: 2.81-10.8) (KL ≥3 vs KL0: 1, OR: 4.09, 95% CI: 2.08-8.03), and presence of KOA (KL ≥3 vs KL0: 1, OR: 1.89, 95% CI: 1.14-3.10) after adjusting for smoking, alcohol consumption, and residential area (mountainous vs coastal). This cross-sectional population-based study clarified the prevalence of DISH in general inhabitants and its significant association with LS and severe KOA.

Mutual associations among musculoskeletal diseases and metabolic syndrome components: A 3-year follow-up of the ROAD study.

OBJECTIVE: This study aimed to assess the mutual associations between musculoskeletal diseases (knee osteoarthritis [KOA], lumbar spondylosis [LS], osteoporosis [OP]) and metabolic syndrome components (obesity [OB], hypertension [HT], dyslipidemia [DL], impaired glucose tolerance [IGT]). METHODS: Of the 1,690 participants (596 men, 1,094 women) at baseline, 1,384 individuals (81.9%; 466 men, 918 women) had complete data at the first follow-up in 2008. Logistic regression analysis included the occurrence or nonoccurrence of the musculoskeletal diseases or metabolic components as the outcome variable and the remaining musculoskeletal diseases and metabolic components at baseline as explanatory variables, adjusted for age, sex, residential region, smoking, and alcohol consumption. RESULTS: The risk of KOA occurring increased significantly with HT (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.22-5.42; p = 0.013) and IGT (OR, 1.99; 95%CI, 1.07-3.70; p = 0.029). The risk of OP occurring at the lumbar spine increased with OP at the femoral neck (OR, 4.21; 95%CI 1.46-12.1; p = 0.008), and vice versa (OR, 2.19; 95%CI, 1.01-479; p = 0.047). KOA increased the risk of HT (Kellgren-Lawrence [KL] grade = 0, 1 vs. KL = 2: OR, 1.84; 95%CI, 1.09-3.12; p = 0.024) and DL (KL = 0, 1 vs. KL ≥ 3: OR, 1.66; 95%CI, 1.05-2.61; p = 0.029) occurring. Reciprocal relationships existed between the presence of metabolic components and the occurrence of the other metabolic components. CONCLUSION: Mutual relationships existed between the occurrence and presence of musculoskeletal diseases, particularly KOA, and metabolic syndrome components.

Lipopolysaccharide preconditioning facilitates M2 activation of resident microglia after spinal cord injury.

The inflammatory response following spinal cord injury (SCI) has both harmful and beneficial effects; however, it can be modulated for therapeutic benefit. Endotoxin/lipopolysaccharide (LPS) preconditioning, a well-established method for modifying the immune reaction, has been shown to attenuate damage induced by stroke and brain trauma in rodent models. Although such effects likely are conveyed by tissue-repairing functions of the inflammatory response, the mechanisms that control the effects have not yet been elucidated. The present study preconditioned C57BL6/J mice with 0.05 mg/kg of LPS 48 hr before inducing contusion SCI to investigate the effect of LPS preconditioning on the activation of macrophages/microglia. We found that LPS preconditioning promotes the polarization of M1/M2 macrophages/microglia toward an M2 phenotype in the injured spinal cord on quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analyses. Flow cytometric analyses reveal that LPS preconditioning facilitates M2 activation in resident microglia but not in infiltrating macrophages. Augmented M2 activation was accompanied by vascularization around the injured lesion, resulting in improvement in both tissue reorganization and functional recovery. Furthermore, we found that M2 activation induced by LPS preconditioning is regulated by interleukin-10 gene expression, which was preceded by the transcriptional activation of interferon regulatory factor (IRF)-3, as demonstrated by Western blotting and an IRF-3 binding assay. Altogether, our findings demonstrate that LPS preconditioning has a therapeutic effect on SCI through the modulation of M1/M2 polarization of resident microglia. The present study suggests that controlling M1/M2 polarization through endotoxin signal transduction could become a promising therapeutic strategy for various central nervous system diseases. © 2014 Wiley Periodicals, Inc.

Midterm results of resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis and the risk factors associated with patient dissatisfaction.

We investigated the midterm results of resection arthroplasty of all 5 metatarsal heads in patients with rheumatoid arthritis and forefoot deformity and analyzed the factors that affect patient satisfaction levels. Of 64 patients (1 male, 63 females), 107 feet were treated with resection arthroplasty for forefoot deformity at our hospital from January 1992 to December 2005. The mean follow-up period was 5.8 ± 3.1 years, with all patients having at least 1 year of follow-up. Of the 64 patients, 75% were satisfied with the surgery. The mean score for the postoperative Japanese Society for Surgery of the Foot lesser metatarsophalangeal-interphalangeal scale was 75.0 ± 15.8 points. Multivariate logistic regression analysis showed that patient-reported dissatisfaction was significantly associated with the recurrence of hammer toe deformity (odds ratio 2.66, 95% confidence interval 1.07 to 6.97), shortening of the resection arthroplasty space (odds ratio 0.85 for a 1-unit increase, 95% confidence interval 0.74 to 0.96), and the recurrence of hallux valgus (odds ratio 1.04 for a 1-unit increase, 95% confidence interval 1.00 to 1.09) during the postoperative period. From our results, interventions to prevent recurrence of hammer toe deformity, especially in toes with preoperative metatarsophalangeal joint dislocations, have been shown to be important in preventing complications and patient dissatisfaction after resection arthroplasty.

Purification and identification of antihypertensive peptides from fermented buckwheat sprouts.

Buckwheat (Fagopyrum esculentum) is rich in antihypertensive compounds. This study investigated the effect of lactic-fermented buckwheat sprouts (neo-FBS) on level, identification, and potency of blood pressure-lowering (BPL) compounds. A single oral dose of 1.0 mg/kg body weight buckwheat sprouts (BS) in spontaneously hypertensive rats did not show significant BPL activity, whereas neo-FBS significantly decreased blood pressure. HPLC of neo-FBS identified two peaks absent in the profile of BS. The peak exhibiting potent BPL activity was fractionated, and six peptides (DVWY, FDART, FQ, VAE, VVG, and WTFR) and tyrosine were identified by LC-MS/MS and Edman degradation. Single oral dose administration of the peptides revealed significant BPL effect of all the peptides, with the most potent being DVWY, FQ, and VVG. DVWY, VAE, and WTFR are novel. This study demonstrates that lactic fermentation of BS produces new, highly potent antihypertensive peptides and increases active compounds GABA and tyrosine already present in BS.

SOX11 contributes to the regulation of GDF5 in joint maintenance.

BACKGROUND: Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis. RESULTS: Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5' UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans. CONCLUSIONS: This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.

Poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liner in primary total hip replacement: one-year results of a prospective cohort study.

To control particle-induced osteolysis in total hip replacement (THR), we developed a new technique to graft poly(2-methacryloyloxyethyl phosphorylcholine) onto the surface of polyethylene liners. A prospective cohort study was conducted to investigate the clinical safety of this novel bearing surface. Between April 2007 and September 2008, we recruited a prospective consecutive series of 80 patients in five participating hospitals. These patients received a cementless THR; a 26-mm-diameter cobalt-chromium-molybdenum alloy ball and a poly(2-methacryloyloxyethyl phosphorylcholine)-grafted cross-linked polyethylene liner were used for the bearing couplings. These individuals were followed a year postoperatively. An evaluation of clinical performance was conducted through an assessment of hip joint function based on the evaluation chart authorized by the Japanese Orthopaedic Association. No patients were lost to follow-up. No adverse events were found to be correlated with the implanted liners. The average hip joint function score improved from 43.2 preoperatively to 91.7 postoperatively at 1 year. There was no implant migration nor periprosthetic osteolysis detected on radiographic analysis. On the basis of our results, we conclude that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted cross-linked polyethylene liners are a safe implant option for hip replacement surgery for short-term clinical use.

Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase B-mediated microtubule stabilization.

We investigated the role of protein kinase B (Akt), a downstream effector of phosphatidylinositol 3-kinase, in bone-resorbing activity of mature osteoclasts. Treatment with a specific Akt inhibitor disrupted sealing zone formation and decreased the bone-resorbing activity of osteoclasts. The normal microtubule structures were lost and the Akt inhibitor reduced the amount of acetylated tubulin, which reflects stabilized microtubules, whereas forced Akt activation by adenovirus vectors resulted in the opposite effect. Forced Akt activation increased the binding of the microtubule-associated protein adenomatous polyposis coli (APC), the APC-binding protein end-binding protein 1 (EB1) and dynactin, a dynein activator complex, with microtubules. Depletion of Akt1 and Akt2 resulted in a disconnection of APC/EB1 and a decrease in bone-resorbing activity along with reduced sealing zone formation, both of which were recovered upon the addition of LiCl, a glycogen synthase kinase-3ß (GSK-3ß) inhibitor. The Akt1 and Akt2 double-knockout mice exhibited osteosclerosis due to reduced bone resorption. These findings indicate that Akt controls the bone-resorbing activity of osteoclasts by stabilizing microtubules via a regulation of the binding of microtubule associated proteins.

Factors affecting the occurrence of pulmonary embolism after spinal surgery: data from the national administrative database in Japan.

BACKGROUND CONTEXT: Despite potentially devastating consequences, pulmonary embolism (PE) in patients undergoing spinal surgery remains poorly understood. To the best of our knowledge, few large studies have examined the prevalence and risk factors of PE after spinal surgery. PURPOSE: To investigate the prevalence of symptomatic PE in patients undergoing elective spinal surgery and to identify clinical variables associated with the occurrence of postoperative PE. STUDY DESIGN: A retrospective analysis of data abstracted from the diagnosis procedure combination (DPC) database, a nationally representative database in Japan. PATIENT SAMPLE: We included all patients with a diagnosis of spinal canal stenosis, disc herniation, spondylosis, spondylolisthesis, trauma, metastatic tumor, or infection who underwent spinal surgery between July 1 and December 31 of 2007 and 2008, respectively. OUTCOME MEASURES: The primary end point was defined as the occurrence of postoperative PE during hospitalization. The secondary end point was in-hospital death after postoperative PE. METHODS: We analyzed the association between the occurrence of postoperative PE and clinical variables recorded in the DPC database, including age, sex, comorbidities, location of surgery, primary diagnosis, anterior/posterior approach, use of instrumentation, and duration of anesthesia. RESULTS: A total of 47,743 patients were identified. Of these, 50 (0.10%) developed PE and four died as a result of PE. Logistic regression analyses revealed that occurrence of PE was associated with older age (70 years or older; odds ratio [OR], 3.15; 95% confidence interval [CI], 1.15-8.69; p=.026) and longer anesthesia time (more than 360 minutes; OR, 2.19; 95% CI, 0.88-5.44; p=.092). Patients with trauma were significantly more likely to have a PE than those with spinal canal stenosis (0.27% vs. 0.09%; OR, 2.86; 95% CI, 1.14-7.18; p=.026). CONCLUSIONS: This retrospective analysis of a nationally representative database identified older age, longer anesthesia time, and spinal trauma as risk factors for increased incidence of postoperative PE. Surgeons should be aware of the increased risk of postoperative PE in these subgroups of patients.

Does mild cognitive impairment affect the occurrence of radiographic knee osteoarthritis? A 3-year follow-up in the ROAD study.

OBJECTIVE: To determine whether mild cognitive impairment (MCI) increases the risk of occurrence or progression of radiographic knee osteoarthritis (KOA) in a general population. DESIGN: Population-based cohort study. SETTING: Residents in mountain and seaside areas of Wakayama Prefecture, Japan. PARTICIPANTS: 1690 participants (596 men, 1094 women; mean age 65.2 years old) were enrolled from the large-scale cohort for the Research on Osteoarthritis (OA)/osteoporosis Against Disability (ROAD) study initiated in 2005 to investigate epidemiological features of OA in Japan. Of these, 1384 individuals (81.9%; 466 men, 918 women) completed the second survey including knee radiography 3 years later. PRIMARY OUTCOME MEASURES: Radiographic KOA was defined as Kellgren-Lawrence (KL) grade ≥ 2 using paired x-ray films. Incidence of KOA during follow-up defined on radiographs as KL grade ≥2, progression of KOA defined as a higher KL grade (either knee) at follow-up compared with baseline. MCI defined as a summary mini-mental state examination (MMSE) score ≤23. Associations between MCI and incidence or progression of KOA were analysed. RESULTS: The annual cumulative incidence of KOA was 3.3%; for progression of OA it was 8.0%. On logistic regression analysis adjusted for age, gender, regional differences, body mass index, grip strength (worse side), smoking, alcohol consumption, regular exercise and history of knee injury, baseline MMSE summary score was significantly associated with the incidence of KOA (+1 MMSE score; OR 0.83, p=0.010). Baseline MCI was also significantly associated with the incidence of KOA (vs non-occurrence of KOA; OR 4.90, p=0.027). There was no significant association between MMSE scores, the presence of MCI and progression of KOA (+1 MMSE score; OR 0.96, p=0.232; vs non-progression of KOA; OR 1.38, p=0.416). CONCLUSIONS: MCI significantly increases the risk of incident radiographic KOA, but not the progression of KOA.