瓦井 裕也

PURPOSE: MIXTURE is a simultaneous morphological and quantitative imaging sequence developed by Philips that provides high-resolution T2 maps from the imaged series. We aimed to compare the T2 maps of MIXTURE and SHINKEI-Quant (S-Q) in the cervical spine and to examine their usefulness in the functional diagnosis of cervical radiculopathy. METHODS: Seven healthy male volunteers (mean age: 31 ± 8.0 years) and one patient with cervical disc herniation (44 years old, male) underwent cervical spine magnetic resonance imaging (MRI), and T2-mapping of each was performed simultaneously using MIXTURE and S-Q in consecutive sequences in one imaging session. The standard deviation (SD) of the T2 relaxation times and T2 relaxation times of the bilateral C6 and C7 dorsal root ganglia (DRG) and C5/6 level cervical cord on the same slice in the 3D T2-map of the cervical spine coronal section were measured and compared between MIXTURE and S-Q. RESULTS: T2 relaxation times were significantly shorter in MIXTURE than in S-Q for all C6, C7 DRG, and C5/6 spinal cord measurements. The SD values of the T2 relaxation times were significantly lower for MIXTURE in the C5/6 spinal cord and C7 DRG. In cervical disc herniation, MRI showed multiple intervertebral compression lesions with spinal canal stenosis at C5/6 and disc herniation at C6/7. CONCLUSION: MIXTURE is useful for preoperative functional diagnosis. T2-mapping using MIXTURE can quantify cervical nerve roots more accurately than the S-Q method and is expected to be clinically applicable to cervical radiculopathy.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) is attracting attention as a minimally invasive surgery, but the learning curve to master this approach is a concern, and its effect on long-term results is unknown. The purpose of this prospective cohort study was to clarify how the learning curve affects the five-year results of DAA THA with a traction table. METHODS: Of 402 THA cases using DAA with a mobile traction table and fluoroscopy, 249 cases composed of the first 50 cases for each surgeon were assessed during a learning curve, and 153 cases were evaluated after more than 50 cases of experience. RESULTS: The five-year-implant survival rate was 99.2% both during and after the learning curve. The two-year complication rate in the learning curve group was 8.9 versus 5.9%, which was not statistically significant. The two-to-five-year complication rates also did not differ between cohorts (0 versus 0.7%). Both groups demonstrated decreased complication rates when comparing two-year complications to the two-to-five-year complications. Clinical scores significantly improved by two years and were maintained at five years in both groups. The cup-safe zone success rates were 96.4% during the learning curve and 98.7% after the learning curve. The stem-safe zone success rates were 97.2% during the learning curve and 96.1% after the learning curve. Surgical time was approximately 20 minutes shorter after the first 50 cases than during the learning curve (70.8 versus 90.6 minutes, P = 0.001). Intraoperative blood loss was significantly less after the learning curve than during the learning curve. CONCLUSION: This study implicates that the learning curve affects perioperative results such as surgical time and intraoperative blood loss, but has little effect on short-term results up to two years after surgery and no effect on mid-term results from two to five years after surgery.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

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.

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.

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.

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.

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.

OBJECTIVES: The pain of hip osteoarthritis is generally recognized as nociceptive in origin because of the local pathology. However, some patients with osteoarthritis 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 osteoarthritis by association of its distribution, complex pain mechanism screening, and the prevalence of lumbar spinal stenosis (LSS). METHODS: We conducted a prospective cross-sectional study of 100 hips in 100 patients with symptomatic hip osteoarthritis 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 (PDQ) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)), and magnetic resonance imaging of the hip and lumbar spine. RESULTS: The PDQ and LANSS 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). LSS 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 osteoarthritis, 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).

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.

AIMS: The main aims were to identify risk factors predictive of a radiolucent line (RLL) around the acetabular component with an interface bioactive bone cement (IBBC) technique in the first year after THA, and evaluate whether these risk factors influence the development of RLLs at five and ten years after THA. METHODS: A retrospective review was undertaken of 980 primary cemented THAs in 876 patients using cemented acetabular components with the IBBC technique. The outcome variable was any RLLs that could be observed around the acetabular component at the first year after THA. Univariate analyses with univariate logistic regression and multivariate analyses with exact logistic regression were performed to identify risk factors for any RLLs based on radiological classification of hip osteoarthritis. RESULTS: RLLs were detected in 27.2% of patients one year postoperatively. In multivariate regression analysis controlling for confounders, atrophic osteoarthritis (odds ratio (OR) 2.17 (95% confidence interval (CI), 1.04 to 4.49); p = 0.038) and 26 mm (OR 3.23 (95% CI 1.85 to 5.66); p < 0.001) or 28 mm head diameter (OR 3.64 (95% CI 2.07 to 6.41); p < 0.001) had a significantly greater risk for any RLLs one year after surgery. Structural bone graft (OR 0.19 (95% CI 0.13 to 0.29) p < 0.001) and location of the hip centre within the true acetabular region (OR 0.15 (95% CI 0.09 to 0.24); p < 0.001) were significantly less prognostic. Improvement of the cement-bone interface including complete disappearance and poorly defined RLLs was identified in 15.1% of patients. Kaplan-Meier survival analysis for the acetabular component at ten years with revision of the acetabular component for aseptic loosening as the end point was 100.0% with a RLL and 99.1% without a RLL (95% CI 97.9 to 100). With revision of the acetabular component for any reason as the end point, the survival rate was 99.2% with a RLL (95% CI 97.6 to 100) and 96.5% without a RLL (95% CI 93.4 to 99.7). CONCLUSION: This study demonstrates that acetabular bone quality, head diameter, structural bone graft, and hip centre position may influence the presence of the any RLL. Cite this article: Bone Joint Open 2021;2(5):278-292.

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.

Introduction A well-fixed cement-bone interface is a crucial factor for acetabular and femoral components in cemented total hip arthroplasty (THA). The aim of the present study was to evaluate the middle-term clinical and radiological results of fixing the acetabular component with an interface bioactive bone cement (IBBC) technique in primary cemented THA. Materials and methods We undertook a retrospective review was undertaken of 193 primary cemented THAs in 174 patients using acetabular components cemented with an IBBC technique and followed for a minimum of 5 years (mean 8.3 years; range 5-17 years). Baseline data, clinical and radiological outcomes were evaluated. Results Japanese Orthopedic Association hip score and modified Harris hip scores demonstrated significant clinical improvement in all patients (p < 0.001). Radiolucent lines were detected in 15 hips (7.8%) at the first year and 24 hips (12.4%) at the final post-operative follow-up. The Kaplan-Meier survivorship with radiographic loosening as the end point was 97.8% [95% confidence interval (CI) 95.2-100]. With revision of the acetabular component for aseptic loosening as the end point, component survival was 99.0% (95% CI 97.5-100). With revision of the acetabular component for any reason as the end point, component survival was 97.0% (95% CI 93.9-100). Conclusions Clinical and radiological results of the acetabular component with the IBBC technique in primary cemented THA were excellent.

Introduction: Ceramic-on-ceramic (COC) total hip arthroplasty (THA) was developed to reduce wear debris, and consequently the occurrence of osteolysis and aseptic loosening. The purpose of the present study was to determine the incidence and natural history of noise including squeaking after COC THA, and to clarify whether clinical outcomes and any demographic and implant-related factors are associated with noise from these ceramic bearings.Methods: This was a retrospective observational study of 137 primary COC THAs between 2004 and 2009 at our institute. The Mean follow-up was for 10.5 years. All patients were followed up with an office visit to obtain information regarding noise, pain, and function. The correlations between the noise, and patient demographic, radiographic, and implant-related factors were evaluated.Results: Noise developed in 30 hips (21.9%), specifically squeaking in 2 (1.5%) of the 137 hips during the followup period. Noise including squeaking was not associated with pain or functional outcomes. There was significant correlation between noise and cup anteversion, in that cup anteversion of patients with noise was smaller than that in those without noise. No significant correlation was found between noise and any other patient demographic including age, sex, height, body weight, or body mass index. Kaplan Meier survivorship analysis with revision for any reason and an aseptic loosening of either component as the end point, revealed a cumulative survival rate at 10 years of 98.4% and 99.1% respectively.Conclusion: The long-term clinical and radiographic outcome of cementless COC THA is excellent, but we should be vigilant for noise from COC bearings.

INTRODUCTION: Little is known about the association between well-fixed polished tapered cemented stems (PTCS) implanted by the line-to-line technique and changes of stem migration, or the change of functional anteversion of the femur after total hip arthroplasty (THA). MATERIALS AND METHODS: This retrospective study included 422 two-stage bilateral primary THAs performed using PTCS implanted by the line-to-line technique. CT scans were made on both the target side (first postoperative CT) and on the contralateral side (second postoperative CT) 1 week postoperatively. The mean follow-up was 7.8 months. CT data for each scan were transferred to 3D template software (Zed hip, Lexi, Japan). The postoperative changes of anatomical stem anteversion (ASA), functional femoral anteversion (FFA), and stem subsidence were evaluated. RESULTS: A total of 20 THAs with CT scans were available on 3D template software. The ASA and the FFA had migrated - 0.68° ± 0.62° and - 5.5° ± 9.7°, respectively, over the follow-up period. A significant positive correlation was observed between the change of subsidence and ASA (r2 = 0.34, p = 0.007), between the FFA on the second postoperative CT and ASA on the first postoperative CT (r2 = 0.26, p = 0.02) and between the FFA on the second postoperative CT and FFA on the first postoperative CT (r2 = 0.52, p = 0.0003). CONCLUSION: This study indicates that the change in axial rotation of a PTCS implanted by the line-to-line technique was less than that reported by other studies and the preoperative external rotation contracture was substantially improved after THA.

Proximal femoral fractures are common in elderly osteoporosis patients; however, its prevalence is clinically rare in hip fracture patients with hip osteoarthritis (OA). This study aimed to evaluate bone strength of the proximal femur with or without hip OA and proximal femoral fracture risk using computed tomography (CT)-based finite element analysis (FEA). A retrospective analysis was done on CT data of 20 patients who underwent total hip arthroplasty for unilateral hip OA. Furthermore, the fracture load between OA and contralateral sides was compared and the association between fracture load and risk factor was analyzed. The fracture load was significantly higher in the OA side than that in the contralateral side (3819.5 ± 1557.8 N vs. 3224.5 ± 943.7 N, respectively; P = 0.0405). There was no significant difference in fracture load between OA and the contralateral side in Kellgren-Lawrence (KL)-3 and KL-4 grade, but the KL-4 fracture load tends to be high (P = 0.2461 and P = 0.0527, respectively). Moreover, there was no significant association between fracture load and OA severity or age. The study findings may assist in predicting bone strength and proximal femur fracture risk. The results of this FEA study indicate the bone strength of the proximal femur was affected by the severity of the osteoarthritis.

Objectives: The goals of this study were to elucidate the distribution of multifocal osteonecrosis associated with glucocorticoid therapy using magnetic resonance imaging (MRI) and to establish a MRI screening method.Methods: Between 1986 and 2018, 107 patients underwent MRI screening of their hips, knees, shoulders and ankle joints (856 joints in total) after systemic glucocorticoid therapy.Results: Osteonecrosis was observed in hip (68%), knee (44%), ankle (17%) and shoulder (15%) joints. Patients with bilateral osteonecrosis in their hips were likely to have bilateral osteonecrosis in their knees, whereas patients without osteonecrosis in both hips were unlikely to have osteonecrosis in both knees (p = .0299). Osteonecrosis was never evident in the ankle or shoulder joints when a patient did not have osteonecrosis in both hip and knee joints.Conclusion: In this study, MRI - as a screening method for multifocal osteonecrosis associated with glucocorticoid therapy - showed the sites affected first are hips and knees followed by ankles and shoulders. If osteonecrosis is absent in hip and knee joints, further screening of the ankles and shoulders is unnecessary. Any osteonecrosis observed in the hip and/or the knee joints warrants a second MRI screening of the ankles and shoulders.

We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 μl of sterile saline and 25 μl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:422-430, 2020.

Objective: The aim was to compare the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the sciatic and femoral nerves in patients with unilateral osteoarthritis of the hip (OA) and osteonecrosis of the femoral head (ONFH) using diffusion tensor imaging (DTI) and to investigate the mechanism of hip pain. Methods: Forty-four patients (22 OA and 22 ONFH) underwent DTI of the sciatic and femoral nerves at the level of the hip joint and the S1 roots to visualize the tractography and quantify the FA and ADC values. Results: The tractography of the femoral and the sciatic nerves on the affected side with OA and ONFH were similar to those on the normal side. The mean FA values of the sciatic and femoral nerves, and the S1 roots were 0.542, 0.551, and 0.316 with OA, 0.568, 0.560, and 0.318 with ONFH on the affected side, and 0.559, 0.560, and 0.315 on the normal side, respectively, and did not show significant differences. The FA values of the sciatic nerve on the affected side with OA decreased with longer pain duration. Conclusion: The FA and ADC values of the sciatic and femoral nerves in patients with unilateral OA and ONFH showed no significant differences between the affected and normal sides.

The aim of this study was to investigate the local production of proinflammatory cytokines, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy-five Sprague-Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N = 25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF-α, immunoreactive (-ir) neurons for calcitonin gene-related peptide (CGRP), and growth associated protein-43 (GAP-43) in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule-1 (Iba-1) in the dorsal horn of spinal cord, on post-induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point). For post-induction days 7-42, the MIA group presented significantly elevated concentrations of TNF-α than the other groups (p < 0.01), and a higher expression of CGRP-ir in FG-labeled DRG neurons than the sham group (p < 0.01). MIA rats also presented significantly more FG-labeled GAP-43-ir DRG neurons than the sham group on post-induction days 28, 42, and 56 (p < 0.05), and a significantly higher number of Iba-1-ir microglia in the ipsilateral dorsal horn than the other groups, on post-induction days 28, 42, and 56. The results suggest that in rat models, pain-related pathologies due to MIA-induced hip OA, originate from inflammation caused by cytokines, which leads to progressive, chronic neuronal damage that may cause neuropathic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2978-2986, 2018.

BACKGROUND: The purpose of this cadaveric study was to clarify the proximal limit for the subvastus approach (SVA) in total knee arthroplasty to decrease potential vascular injury. METHODS: Seventy embalmed knees underwent a modified SVA using a 14-cm oblique medial incision. Anatomical features of the descending genicular artery (DGA) were investigated with regard to variation, distance of the vessels from surgical landmarks, and sex differences. RESULTS: The DGA was identified in 62 knees (89%), while it was absent in 8 knees (11%); in the latter, the articular, saphenous, and muscular branches arose separately from the femoral artery. The mean distances from the tibial tuberosity and medial joint line to the origin of the DGA were 15.5 ± 1.6 cm and 12.6 ± 1.6 cm, respectively. Both distances were significantly longer in males than in females (P < .01, respectively). A strong positive correlation was found between the distance from the tibial tuberosity to the origin of the DGA and the distance from the medial joint line to the origin of the DGA (Spearman's correlation coefficient, R2 = 0.72, P < .01). A weak positive correlation was found between the distance from the tibial tuberosity to the origin of the DGA and lower leg length (R2 = 0.13, P < .01). No vascular injuries were observed in this surgical exposure. CONCLUSION: The DGA showed several variations and was absent 11% of the time. An oblique medial incision within 14 cm from the tibial tuberosity followed by arthrotomy is considered a safe zone for the SVA.

BACKGROUND: The purpose of this study was to validate a diaphyseal femoral fracture model using a finite element analysis (FEA) with mechanical testing in fresh-frozen cadavers. METHODS: We used 18 intact femora (9 right and 9 left) from 9 fresh-frozen cadavers. Specimens were obtained from 5 males and 4 females with a mean age of 85.6 years. We compared a computed tomography (CT)-based FEA model to diaphyseal femoral fracture loads and stiffness obtained by three-point bending. Four material characteristic conversion equations (the Keyak, Carter, and Keller equations plus Keller's equation for the vertebra) with different shell thicknesses (0.3, 0.4, and 0.5 mm) were compared with the mechanical testing. RESULTS: The average fracture load was 4582.8 N and the mean stiffness was 942.0 N/mm from actual mechanical testing. FEA prediction using Keller's equation for the vertebra with a 0.4-mm shell thickness showed the best correlations with the fracture load (R2 = 0.76) and stiffness (R2 = 0.54). Shell thicknesses of 0.3 and 0.5 mm in Keller's equation for the vertebra also showed a strong correlation with fracture load (R2 = 0.66 for both) and stiffness (R2 = 0.50 and 0.52, respectively). There were no significant correlations with the other equations. CONCLUSION: We validated femoral diaphyseal fracture loads and stiffness using an FEA in a cadaveric study.

BACKGROUND: Preoperative planning is an important factor for total knee arthroplasty (TKA). The aim of this study is to document the interobserver and intraobserver reliability of computed tomography (CT)-based 3-dimensional (3D) preoperative planning for primary TKA. METHODS: Twenty knees (10 with osteoarthritis and 10 with rheumatoid arthritis) were studied independently by 6 orthopedic surgeons using a CT-based 3D planning system. The measurements were made twice at more than 3-week intervals without any knowledge of their own previous measurements or those of the others. We assessed the femoral and tibial component sizes and the alignment of the femoral component. RESULTS: The interobserver and intraobserver agreements for femoral component size were 44.3% and 62.5% with exact size, and increased to 90.7% and 99.2% within one size difference; the intraclass correlation coefficients (ICCs) were 0.919 and 0.936, respectively. The interobserver and intraobserver agreements for tibial component size were 57.0% and 66.7% with exact size, and increased to 87.3% and 90.0% within one size difference; the ICCs were 0.909 and 0.924, respectively. The ICCs for femoral and tibial size were better in rheumatoid arthritis than in osteoarthritis. Interobserver ICC for femoral valgus angle was 0.807, and 0.893 for intraobserver reliability. Interobserver ICC of the femoral external rotation angle was 0.463, and 0.622 for intraobserver reliability. CONCLUSION: CT-based 3D preoperative planning for primary TKA has clinical implications for predicting appropriate size and alignment of the component in patients with osteoarthritis and rheumatoid arthritis.

Objective: The purpose of this study was to investigate transitional changes in the incidence of glucocorticoid-associated osteonecrosis in SLE patients, with a focus on immunosuppressive agent and glucocorticoid consumption. Methods: We retrospectively registered 185 SLE patients with 740 joints, who were newly diagnosed and hospitalized for initial high-dose glucocorticoid therapy from 1986 to 2015. Immunosuppressive agent, glucocorticoid dose, age, sex, organ lesion at hospitalization, complement (C3, C4, CH50) and anti-DNA antibody before initial glucocorticoid therapy, the frequency of use of anticoagulant and antilipidemic drugs, and incidence of osteonecrosis were documented. Results: Based on trends in immunosuppressive agent use, 116 patients treated from 1986 to 1999, before calcineurin inhibitors were introduced, comprised the past group, and 69 patients treated from 2000 to 2015 comprised the recent group. Patient characteristics (age, sex and organ lesion at hospitalization, complement, anti-DNA antibody, the frequency of use of anticoagulant and antilipidemic drugs) were similar between groups. Glucocorticoid doses were significantly lower in the recent group than in the past group (highest daily glucocorticoid dose, 45.7 vs 59.0 mg/day, respectively; dose per weight, 0.88 vs 1.16 mg/day/kg, respectively; and cumulative dose at 3 months, 3118 vs 3985 mg). The incidence of osteonecrosis was significantly lower in the recent group than in the past group (26.4 vs 41.0%, respectively), particularly in the knee (25.4 vs 46.6%, respectively). Conclusion: The incidence of glucocorticoid-associated osteonecrosis in SLE patients decreased in association with a decrease in glucocorticoid administration after introduction of immunosuppressant agents.

BACKGROUND: The purpose of this study is to clarify interobserver and intraobserver reliabilities of the three-dimensional (3D) templating of total hip arthroplasty (THA). METHODS: We selected preoperative computed tomography from 60 hips in 46 patients (14 men and 32 women) who underwent primary THA. To evaluate interobserver and intraobserver reliability, 6 orthopedic surgeons performed 3D templating twice over a 4-week interval. We investigated intraclass correlation coefficients (ICCs) and percent agreement of component size and alignment, comparing morphological differences in the hip. Reproducibility was also compared between groups with osteoarthritis (OA) and those with osteonecrosis (ON). RESULTS: The interobserver reliabilities for mean cup size and stem size were excellent, with ICC = 0.907 and 0.944, respectively. The value was significantly higher in the ON group than in the OA group. In the OA group, the reliability of cup size and alignment decreased in hips with severe subluxation. Percent agreement of stem size was significantly different between the shapes of femoral canal. For intraobserver reliability, the mean ICC of cup size was 0.965 overall, while the value in the ON group was significantly higher than in the OA group. The mean ICC of stem size was 0.972 overall. CONCLUSION: Computed tomography-based 3D templating showed excellent reliability for component size and alignment in THA. Deformity of the affected joint influenced the reliability of preoperative planning.

BACKGROUND: Finite element analysis (FEA) of the proximal femur has been previously validated with large mesh size, but these were insufficient to simulate the model with small implants in recent studies. This study aimed to validate the proximal femoral computed tomography (CT)-based specimen-specific FEA model with smaller mesh size using fresh frozen cadavers. METHODS: Twenty proximal femora from 10 cadavers (mean age, 87.1 years) were examined. CT was performed on all specimens with a calibration phantom. Nonlinear FEA prediction with stance configuration was performed using Mechanical Finder (mesh,1.5 mm tetrahedral elements; shell thickness, 0.2 mm; Poisson's coefficient, 0.3), in comparison with mechanical testing. Force was applied at a fixed vertical displacement rate, and the magnitude of the applied load and displacement were continuously recorded. The fracture load and stiffness were calculated from force-displacement curve, and the correlation between mechanical testing and FEA prediction was examined. RESULTS: A pilot study with one femur revealed that the equations proposed by Keller for vertebra were the most reproducible for calculating Young's modulus and the yield stress of elements of the proximal femur. There was a good linear correlation between fracture loads of mechanical testing and FEA prediction (R2 = 0.6187) and between the stiffness of mechanical testing and FEA prediction (R2 = 0.5499). There was a good linear correlation between fracture load and stiffness (R2 = 0.6345) in mechanical testing and an excellent correlation between these (R2 = 0.9240) in FEA prediction. CONCLUSIONS: CT-based specimen-specific FEA model of the proximal femur with small element size was validated using fresh frozen cadavers. The equations proposed by Keller for vertebra were found to be the most reproducible for the proximal femur in elderly people.

PURPOSE: The purpose of this study was to clarify the difference in implant alignment between the direct anterior approach (DAA) and the anterolateral approach in the supine position (ALS). METHODS: A retrospective comparative study consisted of 215 consecutive primary total hip arthroplasties using tapered polished and straight cemented-stems via two different minimally invasive approaches (DAA group in 106 hips and ALS group in 109 hips). RESULTS: The cup radiographic anteversion angle was significantly lower in the ALS group than in the DAA group (12.9° versus 16.9°, p = 0.001). The frequency of the safe zone tended to be more favourable in the ALS group than in the DAA group (95% versus 87%, p = 0.052). Stem alignment in the sagittal plane was significantly better in the ALS group than in the DAA group (84% versus 71%, p = 0.022). CONCLUSIONS: Both cup and stem alignments were better in the ALS group than the DAA group.

BACKGROUND: The aim was to clarify the normal fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the sciatic and femoral nerves at the level of the hip joint and to visualize the neural tracts with diffusion tensor imaging (DTI). METHODS: Twenty-four healthy volunteers (12 men and 12 women, age 20-29 years) underwent DTI for visualization with tractography and quantification of FA and ADC values on a 3 Tesla MRI (b value = 800 s/mm2, motion probing gradient, 11 directions, time to repeat/echo time = 9000/72.6 ms, axial slice orientation, slice thickness = 3.0 mm with no inter-slice gap, field of view = 320 × 320 mm, 96 × 192 matrix, 75 slices, number of acquisitions = 4). Regions of interest in the sciatic nerve were defined at the femoral head, the S1 root, and the midpoint levels. The femoral nerve was evaluated at 3-4 cm proximal to the femoral head level. RESULTS: The tractography of the sciatic and femoral nerves were visualized in all participants. The mean FA values of the sciatic nerve were increased distally from the S1 root level, through the midpoint, and to the femoral head level (0.314, 0.446, 0.567, p = 0.001, respectively). The mean FA values of the femoral nerve were 0.565. The mean ADC values of the sciatic nerves were significantly lower in the S1 root level than in the midpoint and the femoral head level (1.481, 1.602, 1.591 × 10-3 × 10-3 mm2/s, p = 0.001, respectively). The ADC values of the femoral nerve were 1.439 × 10-3 mm2/s. FA and ADC values showed moderate to substantial inter- and intra-observer reliability without significant differences in gender or laterality. CONCLUSION: Visualization and quantification of the sciatic and femoral nerves simultaneously around the hip joint were achieved in healthy young volunteers with DTI. Clinical application of DTI is expected to contribute to hip pain research.

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported. MATERIALS AND METHODS: TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating the femurs of Sprague Dawley rats were examined in control, sham, and ovariectomized (OVX) rats. We evaluated osteoporosis in the femurs and compared the proportion of TRPV1-ir DRG neurons innervating femur between the 3 groups of rats. RESULTS: OVX rats showed osteoporotic cancellous bone in the femur. FG labeled neurons were distributed from L1 to L6 DRG, but there was no significant difference in the proportion of labeled neurons between the 3 groups (p>0.05). The proportions of FG labeled TRPV1-ir DRG neurons were 1.7%, 1.7%, and 2.8% of DRG neurons innervating the femur, in control, sham-operated, and OVX rats, respectively. The proportion of TRPV1-ir neurons in DRG innervating the femur in OVX rats was significantly higher than that in control and sham-operated rats (p<0.05). CONCLUSION: Under physiological conditions, DRG neurons innervating femurs in rats contain TRPV1. Osteoporosis increases the numbers of TRPV1-ir neurons in DRG innervating osteoporotic femurs in rats. These findings suggest that TRPV1 may have a role in sensory perception of osteoporotic femurs.

PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.

STUDY DESIGN: Basic pain study using osteoporotic rodent models. OBJECTIVE: To examine alterations in distribution of pain-related neuropeptides after compressive force on osteoporotic vertebrae and their chronic pain-related properties. SUMMARY OF BACKGROUND DATA: We previously reported significantly increased production of calcitonin gene-related peptide (CGRP), a marker of inflammatory pain, in the dorsal root ganglia (DRG) of vertebrae in osteoporosis-model ovariectomized (OVX) rats. Here, we hypothesized that longitudinal compressive force on vertebrae can affect osteoporotic pain properties, which has not been examined yet. METHODS: OVX rats were used as the osteoporosis model. Female Sprague-Dawley rats were prepared and Fluoro-Gold (FG) neurotracer was applied to the periosteal surface of the Co5 vertebra. After FG labeling, the animals were divided into 4 groups: Control, Control + compression, OVX, and OVX + compression. The Control groups were not ovariectomized. In the compression groups, K-wires were stabbed transversely through Co4 and Co6 with Co5 compressed longitudinally by rubber bands bridged between the 2. One, 2, 4, and 8 weeks after surgery, bilateral S1 to S3 DRGs were excised for immunofluorescence assays. Expression of CGRP and activating transcription factor 3, a marker of neuronal injury, were compared among the 4 groups. RESULTS: Sustained upregulation of CGRP in DRG neurons was observed after compression of the Co5 vertebra, and Co5 compression caused significant increase in CGRP production in DRG neurons, whereas a greater level of activating transcription factor 3 upregulation was observed in DRGs in OVX rats after dynamic vertebral compression 8 weeks after surgery, implying potential neuropathic pain. CONCLUSION: There was sustained upregulation of CGRP and activating transcription factor 3 in DRGs in osteoporotic model rats compared with controls, and levels were further enhanced by dynamic vertebral compression. These findings imply that dynamic compression stress on vertebrae can exacerbate osteoporotic pain by inducing both inflammatory and neuropathic pain mediators. LEVEL OF EVIDENCE: N/A.