Junichi Nakamura

Psychological stress affects the immune system and exacerbates autoimmune diseases such as rheumatoid arthritis (RA), but the mechanisms underlying tissue inflammation during remission remain unclear. Here, we show that tube restraint stress exacerbates joint inflammation in a murine arthritis model during remission. This exacerbation required interleukin-6 (IL-6) produced by brown adipose tissue (BAT) following sympathetic activation. Fibroblast-like synoviocytes expressing the IL-6 receptor subunit gp130 were critical mediators, as IL-6 stimulated these cells to produce the neutrophil chemoattractant CXCL1. Pharmacological blockade of the β3-adrenergic receptor significantly attenuated stress-induced arthritis flares. In patients with RA, carriers of the hypofunctional Trp64Arg variant of ADRB3 showed no positive correlation between psychological stress and disease activity, whereas noncarriers did. These findings identify a BAT–IL-6–fibroblast axis that reactivates inflammatory memory in arthritis and suggest that targeting stress-responsive pathways may provide a complementary therapeutic strategy alongside current RA treatments without broadly suppressing systemic immunity.

Background: Conventional safe zones are defined by the proximity of acetabular cup screws to intrapelvic vessels; however, this relationship varies among individuals. This study aimed to define the intraosseous safe zone in which the screws remain entirely within bone without penetrating the medial wall. Methods: Three-dimensional computed tomography data for 30 hips of female patients with normal acetabular morphology were analyzed. A hemispherical cup was positioned virtually, and screw trajectories were evaluated in 24 directions using a clock-face coordinate system referenced to the ipsilateral anterior superior iliac spine. Bone thickness was measured in each direction, and intraosseous safe zones were defined for screw lengths of 15, 20, 25, 30, 40, and 50 mm. Heatmaps were generated to visualize the distribution of safe regions, and the angular range in which screws remained intraosseous in all cases was determined. Results: The median patient age was 50.1 years. The intraosseous safe zone was consistently located in the posterosuperior region for all screw lengths. The extent of the safe zone significantly decreased as the screw length increased (p < 0.01), whereas shorter screws expanded the safe zone toward the posteroinferior region. The angular range of the intraosseous safe zone was consistently the greatest at the 11 and 11:30 o’clock positions for 15, 20, and 25 mm screws. Conclusions: The findings provide a useful framework for preoperative planning and conceptualizing safe screw trajectories in total hip arthroplasty. Clinical Relevance: Directing screws toward the posterosuperior acetabulum, particularly around the 11 o’clock region, may enhance safety by maintaining intraosseous fixation and avoiding intrapelvic neurovascular injury. Shorter screws may expand safe fixation options toward the posteroinferior region.

Background: Range of motion (ROM) after total hip arthroplasty (THA) is influenced by implant-related parameters such as femoral head diameter, neck length, and stem offset. However, the quantitative effects of these parameters on ROM, leg length discrepancy (LLD), and femoral offset discrepancy remain unclear. This study aimed to quantify the effects of implant-related parameters on simulated impingement-free mechanical ROM after unilateral THA. Methods: A computed tomography (CT) -based three-dimensional (3D) simulation was performed in 100 patients who underwent unilateral THA with a clinically and radiographically healthy contralateral hip. The contralateral healthy hip was also evaluated as a patient-specific comparator. Implant configurations were simulated by varying femoral head diameter, neck length, and stem offset. Femoral head diameters of 36 mm and 32 mm, neck lengths from − 3.5 mm to + 7 mm, and standard-offset and lateral-offset stems were evaluated. Simulated impingement-free mechanical ROM was assessed in maximum flexion, maximum extension, internal rotation at 90° of flexion, and external rotation at 10° of extension. Simulated LLD and femoral offset discrepancy relative to the contralateral healthy hip were also quantified. Results: Increasing neck length improved simulated mechanical ROM in all evaluated directions, with median increases of 6.3° in flexion and 5.3° in extension for every 3.5-mm increment. Lateral offset stems further increased flexion by 16.3° compared with standard stems. Femoral head enlargement from 32 mm to 36 mm modestly improved simulated mechanical ROM, increasing flexion by approximately 2.5°. However, neck lengthening increased LLD by a median of 2.3 mm per 3.5-mm increment. The contralateral healthy hips showed median simulated ROM values of 119° in flexion, 66° in extension, 31° in internal rotation, and 48° in external rotation. Conclusions: Increasing neck length and lateral offset improved simulated impingement-free mechanical ROM after unilateral THA, whereas neck lengthening increased LLD. Femoral head enlargement also improved simulated mechanical ROM, but its effect was limited compared with those of neck length and stem offset. The contralateral healthy hip may provide contextual patient-specific information for interpreting simulated mechanical ROM in unilateral THA.

Background: This study aimed to characterize pain-related mechanisms and the bone-destructive environment in mild and severe monoiodoacetate (MIA)-induced hip arthropathy in rats, with particular focus on features relevant to rapidly destructive coxarthrosis. Methods: Rats were divided into sham, low-dose MIA, and high-dose MIA groups ( n = 12 per group) and received intra-articular injections of saline, low-dose MIA, or high-dose MIA, respectively. Pain-related behaviors were assessed using von Frey and weight-bearing tests. Radiological and histological changes were evaluated using microcomputed tomography and the Osteoarthritis Research Society International scoring system. The proportion of calcitonin gene-related peptide (CGRP)-immunoreactive dorsal root ganglion (DRG) neurons and the number of ionized calcium-binding adaptor molecule 1 (Iba1)-immunoreactive microglia in the spinal dorsal horn were quantified immunohistochemically. Synovial mRNA expression of tumor necrosis factor-α ( Tnf-α ) and receptor activator of nuclear factor-kappa B ligand ( Rankl ), as well as osteoclast-like multinucleated cells in the femoral head, were also quantified. Results: The high-dose MIA group showed significantly greater mechanical hypersensitivity and reduced weight-bearing capacity than the low-dose MIA and sham groups. This group also demonstrated more severe joint destruction, higher OARSI scores, a higher proportion of CGRP-immunoreactive DRG neurons, and an increased number of Iba1-immunoreactive microglia in the spinal dorsal horn. Synovial Tnf-α and Rankl mRNA expression levels were significantly increased in the high-dose MIA group compared with those in the sham and low-dose MIA groups. These changes were accompanied by an increased number of osteoclast-like multinucleated cells and bone resorption cavities compatible with Howship’s lacunae in the femoral head. Conclusions: High-dose MIA-induced hip arthropathy was characterized by more severe pain-related behavior, a higher proportion of CGRP-immunoreactive DRG neurons, an increased number of Iba1-immunoreactive microglia in the spinal dorsal horn, and a more pronounced osteoclast-associated bone-destructive environment than low-dose MIA-induced hip arthropathy. These findings suggest that the high-dose MIA model exhibits several experimental features relevant to rapidly destructive hip disease.

Introduction: Impaction bone grafting (IBG) with cemented stems in revision total hip arthroplasty (THA) is a well-established method, but reports using cementless stems are scarce. The purpose of this study is to report short-term outcomes of six revision THAs using the IBG technique with a collared fully hydroxyapatite (HA)-coated stem. Materials and Methods: From 2014 to 2021, six joints (median age 64.3 years; median follow-up 4.5 years) were revised for aseptic loosening (n = 5) or septic loosening (n = 1). All cases used the IBG technique with a collared fully HA-coated stem (CORAIL or UNIVERSIA). Full weight-bearing was allowed post-operative day 1. Outcomes included the Japanese Orthopedic Association Score, stem subsidence, and radiographic remodeling. Results: Median surgical time was 127 min; blood loss was 855 mL. No complications (infection, polyethylene wear, loosening, or dislocation) occurred. The JOA score improved from 63 (preoperatively) to 95 (final follow-up). Median stem subsidence was 1.4 mm (1–3 mm), with no case >5 mm. Radiographs showed no radiolucent lines and remodeling in all cases. Computed tomography (CT) images of one case confirmed bone ingrowth between the stem and the compressed allograft. Conclusion: Short-term outcomes of revision THA with IBG using a collared fully HA-coated stem are favorable. This technique, supported by radiographic and CT evidence of bone ingrowth, is a useful and effective treatment option for femoral component revision.Short-term outcomes of revision THA with IBG using a collared fully HA-coated stem are favorable. This technique, supported by radiographic and CT evidence of bone ingrowth, is a useful and effective treatment option for femoral component revision. Keywords: Impaction bone grafting, collared fully hydroxyapatite-coated stem, revision total hip arthroplasty

Restoration of the hip center of rotation (COR) is a primary goal in total hip arthroplasty (THA). Although the teardrop has been widely used as a reference for acetabular cup positioning, its effect on offsets remains uncertain. We conducted a computed tomography–based simulation study of 60 hips (30 osteoarthritis, 30 osteonecrosis of the femoral head) undergoing THA. The contralateral, unaffected hip served as the control. The acetabular cup was positioned just lateral to the teardrop, aligned with the true floor of the acetabulum using preoperative templating software. Acetabular, femoral, and vertical offsets (AO, FO, and VO) were measured bilaterally, and the horizontal and vertical displacements of the COR were evaluated. Compared to the contralateral unaffected side, AO and FO significantly decreased and VO significantly increased on the surgical side ( p < 0.01). The COR shifted medially and superiorly in both OA and ONFH groups (average: 2.7–2.8 mm medial, 2.0–2.8 mm superior). In the OA group, global offset (GO), the sum of AO and FO, decreased by 4.7 mm due to a significant reduction in FO. Teardrop‐based positioning of the acetabular cup results in medial and superior displacement of the COR, consequently reducing AO and GO. In patients with osteoarthritis, a decreased FO further compromises GO, making femoral component adjustment essential for biomechanical restoration. Further investigation into the clinical ramifications of these offset changes is warranted.

Diclofenac etalhyaluronate combines the sustained‐release properties of diclofenac with the therapeutic benefits of hyaluronic acid, providing extended analgesic effects for osteoarthritis management. This study investigated the effects of diclofenac etalhyaluronate and subsequent osteoarthritic changes in rat models of advanced and end‐stage osteoarthritis. Monosodium iodoacetate (0.5 or 2.0 mg) was injected directly into the right hip joint of rats (n = 8 rats/group) using a posterior approach to induce osteoarthritis. Four weeks after monosodium iodoacetate administration, diclofenac etalhyaluronate (0.25 mg/25 µL) or 25 µL saline was administered in the same way. Pain behavior, number of microglia in the dorsal horn of the spinal cord, radiological features on microcomputed tomography, and histology of the hip joint were evaluated. Administration of diclofenac etalhyaluronate increased the pain threshold and reduced the number of microglia in the dorsal horn of the spinal cord in both models. However, radiological and histological examinations did not detect significant arthritic changes in either group that received diclofenac etalhyaluronate. Intra‐articular administration, therefore, contributes to pain relief and improvement of central sensitization in advanced and end‐stage osteoarthritis of the hip without subsequent progression of osteoarthritis. These findings highlight the potential of intra‐articular administration of diclofenac etalhyaluronate as a conservative treatment option for advanced and end‐stage hip osteoarthritis, particularly for patients who may be unsuitable for surgery or have limited response to oral nonsteroidal anti‐inflammatory drugs.