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Background: This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. Methods: Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. Results: The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten–eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. Conclusions: The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Context: Chronic low back pain (LBP) is a multifactorial disorder with complex underlying mechanisms, including associations with intervertebral disc (IVD) degeneration in some individuals. It has been demonstrated that epigenetic processes are involved in the pathology of IVD degeneration. Epigenetics refers to several mechanisms, including DNA methylation, that have the ability to change gene expression without inducing any change in the underlying DNA sequence. DNA methylation can alter the entire state of a tissue for an extended period of time and thus could potentially be harnessed for long-term pain relief. Lifestyle factors, such as physical activity, have a strong influence on epigenetic regulation. Exercise is a commonly prescribed treatment for chronic LBP, and sex-specific epigenetic adaptations in response to endurance exercise have been reported. However, whether exercise interventions that attenuate LBP are associated with epigenetic alterations in degenerating IVDs has not been evaluated.Purpose: We hypothesize that the therapeutic efficacy of physical activity is mediated, at least in part, at the epigenetic level. The purpose of this study was to use the SPARC-null mouse model of LBP associated with IVD degeneration to clarify (1) if IVD degeneration is associated with altered expression of epigenetic regulatory genes in the IVDs, (2) if epigenetic regulatory machinery is sensitive to therapeutic environmental intervention, and (3) if there are sex-specific differences in (1) and/or (2).Study Design: Eight-month-old male and female SPARC-null and age-matched control (WT) mice (n=108) were assigned to exercise (n=56) or sedentary (n=52) groups. Deletion of SPARC is associated with progressive IVD degeneration and behavioral signs of LBP. The exercise group received a circular plastic home cage running wheel on which they could run freely. The sedentary group received an identical wheel secured in place to prevent rotation. After 6 months, the results obtained in each group were compared.Methods: After 6 months of exercise, LBP-related behavioral indices were determined, and global DNA methylation (5-methylcytosine) and epigenetic regulatory gene mRNA expression in IVDs were assessed. This project was supported by the Canadian Institutes for Health Research. The authors have no conflicts of interest.Results: Lumbar IVDs from WT sedentary and SPARC-null sedentary mice had similar levels of global DNA methylation (%5-mC) and comparable mRNA expression of epigenetic regulatory genes (Dnmt1,3a,b, Mecp2, Mbd2a,b, Tet1-3) in both sexes. Exercise attenuated LBP-related behaviors, decreased global DNA methylation in both WT (p<.05) and SPARC-null mice (p<.01) and reduced mRNA expression of Mecp2 in SPARC-null mice (p<.05). Sex-specific effects of exercise on expression of mRNA were also observed.Conclusions: Exercise alleviates LBP in a mouse model. This may be mediated, in part, by changes in the epigenetic regulatory machinery in degenerating IVDs. Epigenetic alterations due to a lifestyle change could have a long-lasting therapeutic impact by changing tissue homeostasis in IVDs.Clinical Significance: This study confirmed the therapeutic benefits of exercise on LBP and suggests that exercise results in sex-specific alterations in epigenetic regulation in IVDs. Elucidating the effects of exercise on epigenetic regulation may enable the discovery of novel gene targets or new strategies to improve the treatment of chronic LBP. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate, using computed tomography (CT) and magnetic resonance imaging (MRI), patients who underwent oblique lateral interbody fusion (OLIF) using either expandable or static interbody spacers. Thirty-five patients with degenerative disc disease were surgically treated with one-level OLIF and were followed up for more than 6 months. The Static group consisted of 22 patients, and 13 patients were in the Expandable group. Intraoperative findings included operative time (min), blood loss (ml), and cage size. Low back pain, leg pain, and leg numbness were measured using the Japanese Orthopedic Association score, visual analogue score, and the Roland–Morris Disability Questionnaire. Radiologic evaluation using computed tomography (CT) and magnetic resonance imaging (MRI) allowed measurement of cage subsidence, cross-sectional area (CSA) of the dural sac, disc height, segmental lordosis, foraminal height, and foraminal CSA preoperatively and 6 months postoperatively. The Expandable group had significantly larger cage height and lordosis than the Static group (P < 0.05). The Expandable group also had greater dural sac area expansion and enlargement of the intervertebral foramen, as well as better correction of vertebral body slip (P < 0.05). Cage subsidence was significantly lower in the Expandable group (P < 0.05). JOA and VAS scores for leg numbness were significantly better in the Expandable group (P < 0.05). Compared with static spacers, expandable spacers significantly enlarged the dural sac area, corrected vertebral body slippage, expanded the intervertebral foramen, and achieved good indirect decompression while reducing cage subsidence, resulting in improvement in clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Femoral neurovascular injury is a serious complication in a direct anterior approach (DAA) total hip arthroplasty. However, dynamic neurovascular bundle location changes during the approach were not examined. Thus, this study aimed to analyze the effects of leg position on the femoral neurovascular bundle location using magnetic resonance imaging (MRI). Methods: This study scanned 30 healthy volunteers (15 males and 15 females) with 3.0T MRI in a supine and 30-degree hip extension position with the left leg in a neutral rotation position and the right leg in a 45-degree external extension position. The minimum distance from the edge of the anterior acetabulum to the femoral nerve (dFN), artery, and vein were measured on axial T1-weighted images at the hip center level, as well as the angle to the horizontal line of the femoral nerve (aFN), artery (aFA), and vein from the anterior acetabulum. Results: The dFN in the supine position with external rotation was significantly larger than supine with neutral and extension with external rotation position (20.7, 19.5, and 19.0; p = 0.031 and 0.012, respectively). The aFA in supine with external rotation was significantly larger than in other postures (52.4°, 34.2°, and 36.2°, p < 0.001, respectively). The aFV in supine with external rotation was significantly larger than in supine with a neutral position (52.3° versus 47.7°, p = 0.037). The aFN in supine and external rotation was significantly larger than other postures (54.6, 38.2, and 33.0, p < 0.001, respectively). Conclusions: This radiographic study revealed that the leg position affected the neurovascular bundle location. These movements can be the risk of direct neurovascular injury or traction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. In primary and revision total hip arthroplasty, to prevent perioperative complications, the prediction of the optimal implant size is essential. Using three-dimensional computed tomography-based postoperative evaluation software, we explored the accuracy and the precision of measurement of the size, alignment, and position of the prosthetic components after total hip arthroplasty. Methods. Using postoperative evaluation software, the postoperative computed tomography data from 20 hips in 20 patients were evaluated. The component size, alignment, and three-dimensional positioning of the cup and stem were assessed. The concordance rates of the component, repeatability (intraobserver reliability), and reproducibility (interobserver reliability) of postoperative evaluation were calculated. The radiographic inclination and radiographic anteversion of the cup, anteversion, varus–valgus angle, and flexion–extension angles of the stem were measured for alignment. The implant positioning was measured along three axes, namely, X-axis (transverse), Y-axis (sagittal), and Z-axis (longitudinal). Results. The concordance rates of all parts are above 94%. The intraobserver and interobserver intraclass correlation coefficients of alignment measurement were very good for both cup (0.879–0.964) and stem (0.973–0.996). The intraobserver and interobserver intraclass correlation coefficients of cup positioning were very good (0.961–0.987) for all axes. The intraobserver and interobserver intraclass correlation coefficients of implant positioning were very good for the stem (0.879–0.995) for all axes. Conclusions. Computed tomography-based postoperative evaluation software was able to evaluate the size and position of total hip implants with high reproducibility. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Proximal femur fracture type can be influenced by the fall direction. • Posterolateral falls are more likely to result in trochanteric fractures than lateral falls. • Equivalent stress is changed depending on the fall direction. • Change of stress may affect the fracture type. [ABSTRACT FROM AUTHOR]