Bone & Joint Research最新文献

Aims: Flexion varus tibial plateau fracture (FVTPF) is associated with a substantial reoperation rate and poor outcomes. This study aims to clarify its fracture characteristics, investigate concomitant ligament and meniscus injuries, and explore correlations between fracture morphology and soft-tissue involvement.

Methods: FVTPF patients with available CT and MRI data were included. Fracture mapping was used to present the fracture line and depression area in a spatial manner. Fracture morphological parameters were measured on CT, and ligament and meniscus injuries were assessed on MRI. Association between fracture morphological parameters and ligament/meniscus injuries was analyzed. Receiver operating characteristic (ROC) analysis was adopted to determine the reliable fracture parameter for diagnosing lateral meniscus (LM) entrapment.

Results: There were 108 patients who met the inclusion criteria. The medial fragment of FVTPF exhibited various morphological patterns, with the posterolateral depression area representing a mean 16.7% (SD 7.0) of the entire plateau. FVTPF cases with comminuted medial fragments were associated with greater lateral plateau widening, maximal depression depth, and medial plateau displacement (p < 0.001, respectively). The rate of anterior cruciate ligament (ACL) avulsion fractures was 85.2% (92 patients). The rate of overall LM injuries was 54.6% (59 patients), which was significantly higher in FVTPF cases with comminuted medial fragments (80.0% (24 patients), p = 0.001). ROC analysis revealed that maximal depression depth was a favourable predictor for LM entrapment, with a cut-off point of 18.4 mm (sensitivity 88.9%; specificity 94.4%).

Conclusion: FVTPF showed various morphologies of the main medial fragment, with the depression area located in the posterolateral plateau. The ACL avulsion fractures were predominant in FVTPF, followed by LM injuries. FVTPF cases with comminuted medial fragments were associated with a significantly higher rate of LM injuries. Among the bony fracture parameters, maximal depression depth showed a considerable value in predicting LM entrapment.

Aims: Chronic proximal hamstring tendon injuries sometimes require surgical reconstruction using a certain type of tendon graft. Although a distal hamstring and an Achilles tendon are the previously reported allograft options for this procedure, it remains unclear which allograft has superior biomechanical properties. The objective is to biomechanically compare the failure load, elongation at failure, and stiffness of proximal hamstring reconstruction techniques, using a semitendinosus tendon allograft and an Achilles tendon allograft. We hypothesized that the reconstruction, using a semitendinosus tendon allograft, would result in superior biomechanical properties.

Methods: Eight pairs of fresh-frozen human cadaveric hemipelvises were obtained, along with Achilles tendon and semitendinosus allografts. Specimens first underwent non-destructive native-state testing to determine linear stiffness. Within each pair, specimens were randomly assigned to reconstruction with either an Achilles tendon or a semitendinosus allograft. Following repair, the specimens underwent uniaxial tension testing consisting of a preconditioning phase and pull-to-failure testing to determine failure load, elongation at failure, stiffness, and mode of failure.

Results: The Achilles tendon allograft group failed at a significantly lower mean load than the semitendinosus group (213 N (SD 48) vs 366 N (SD 85); p = 0.005). Failure in the Achilles group occurred exclusively via suture pullout at the proximal end of the graft. Repairs with semitendinosus grafts most often failed by the same mechanism. Mean percent difference of native stiffness was significantly higher in the Achilles group compared to the semitendinosus group (34.4% (SD 14.1%) vs 13.1% (SD 6.4%); p = 0.003).

Conclusion: Proximal hamstring reconstruction with a semitendinosus tendon allograft showed higher failure load and better preservation of native stiffness compared to an Achilles tendon allograft using the techniques described in this study. While construct differences may contribute to this result, these findings support semitendinosus as the strongest allograft option for proximal hamstring reconstruction.

Aims: This study aimed to assess the effects of chondrogenic agents kartogenin (KGN) and KA9 in combination with anakinra (ANR), an interleukin (IL) 1 receptor antagonist (IL1RA) on post-traumatic osteoarthritis (PTOA) progression following intra-articular fractures (IAF). The hypothesis was that this immunoregenerative approach would promote osteochondral healing and alleviate PTOA more effectively than individual treatments or controls.

Methods: Male Lewis rats (n = 78) underwent IAF, followed by weekly intra-articular injection of saline (control), KGN, or KA9 in conjunction with the systemic administration of saline (control) or ANR via osmotic pumps. Inflammatory and osteochondral markers were assessed through serum and synovial fluid analysis, micro-CT (µCT) for bone parameters, contrast-enhanced µCT for cartilage evaluation, histopathological analysis, and immunohistochemistry (IHC).

Results: Immunoregenerative treatments did not adversely affect animal wellbeing. While local inflammation markers were minimally affected, some osteochondral remodelling markers indicated that KGN, KA9, and their combination with ANR reduced markers of osteochondral degradation. Bone analysis showed improved trabecular morphometry parameters and reduced bone surface with some treatments, and cartilage composition and thickness improved with treatments, although the effects were inconsistent across groups. Osteoarthritis Research Society International scores revealed location-specific variations in pathology, and IHC staining demonstrated intergroup differences in protein expression at different timepoints.

Conclusion: This study suggests that KGN and KA9 may offer some protection against PTOA by influencing cartilage and subchondral bone health, and that the combination with ANR shows potential for enhanced effects. However, the results were mixed, with no treatment group consistently demonstrating positive improvements across all outcomes. The complexity of developing a novel immunoregenerative therapy for PTOA is highlighted by the variability in treatment response.

Aims: Osteoporosis (OP), an age-related skeletal disorder, is characterized by excessive bone resorption driven by osteoclast overactivation, reactive oxygen species (ROS) accumulation, and chronic inflammation. Although the mitochondria-targeted antioxidant ergothioneine (EGT) has shown potential in regulating bone metabolism, its specific preventive mechanism in oestrogen-deficient osteoporosis remains unclear. Therefore, this study aimed to elucidate the preventive effects of EGT and its underlying mechanisms when administered early after ovariectomy.

Methods: Using an oestrogen-deficient mouse model, EGT was administered immediately after modelling to evaluate its preventive effects against bone loss and microstructural deterioration. In vivo analyses included assessments of bone resorption parameters, B-cell precursor populations, and the bone marrow inflammatory status. Complementary in vitro experiments were conducted to examine the influence of EGT on mitochondrial ROS levels, p65 phosphorylation, NF-κB/NFATc1 signalling pathway activity, and osteoclast differentiation.

Results: Preventive administration of EGT significantly mitigated ovariectomy-induced bone loss and preserved bone microstructure. This was achieved through the suppression of osteoclast activity, modulation of B-cell precursors, and reversal of the pro-inflammatory bone marrow microenvironment. Mechanistically, EGT reduced mitochondrial ROS generation, inhibited p65 phosphorylation and nuclear translocation, and consequently disrupted the nuclear factor κB (NF-κB)/NFATc1 signalling axis, ultimately inhibiting osteoclastogenesis.

Conclusion: The findings of this study indicate that ergothioneine has the potential to prevent osteoporosis. It bidirectionally regulates bone homeostasis by targeting the ROS-NF-κB axis, systemically remodelling a protective anti-inflammatory bone marrow microenvironment while directly inhibiting osteoclast activation and differentiation. These results underscore the translational value of EGT as an early preventive strategy for oestrogen-deficient osteoporosis.

Aims: This study examines the ability of YOLO (You Only Look Once) 11x, a widely used and state of the art object detection model, trained on publicly available datasets, to identify and count neutrophils in tissue samples taken at prosthetic joint revision surgery, with the objective of automating a laborious but necessary part of the diagnostic workup for periprosthetic joint infection.

Methods: Three datasets containing blood film microscopic slides with neutrophils were downloaded, combined, and labelled. The resulting dataset of 3,923 images was augmented with ten additional histological slides from periprosthetic tissue, taken at the time of revision surgery (5 infected, 5 sterile), and split into training (70%), validation (20%), and test (10%) sets. The dataset was used to train YOLO 11x object detection model optimized for a mean average precision above 50%. The trained network was tested on a ground truth specimen and histological whole slide images from 19 additional cases, previously unseen by the model, for validation. The threshold for diagnosis of infection on histological sections was set at more than five neutrophils per 0.2 mm² (equivalent to one high-powered microscope field).

Results: The model performed well as ground truth image returned precision at 82%, recall (sensitivity) 79%, and F1 harmonic mean 80%. When assessed against formal histopathological, microbiological, and multidisciplinary team (MDT) diagnosis, precision was 78%, 80%, and 90%; recall 78%, 89%, and 82%; and F1 score 78%, 84%, and 86%, respectively. Against the definitive MDT diagnosis, our model identified nine out of the ten infected cases and excluded seven out of nine cases that were not infected.

Conclusion: This study demonstrates ability of the trained model to identify neutrophils in tissue taken at revision surgery and could assist in diagnosis of periprosthetic infection. Further work is needed to improve confidence in the identifications and diagnostic accuracy of periprosthetic infection.

Aims: High serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased risk of fracture; however, it remains unclear whether lowering LDL-C reduces fracture risk, and, if so, whether the magnitude of LDL-C reduction is linearly associated with fracture risk. This study aimed to evaluate the relation between the degree of LDL-C reduction and fracture risk.

Methods: This population-based cohort study included individuals aged 40 to 90 years who initiated statins for hyperlipidaemia from IQVIA Medical Research Data primary care database in the UK (2000 to 2022). The primary outcome was hip fracture. Secondary outcomes included composite fracture and major osteoporotic fracture. A hypothetical target trial was emulated to assess the effect of achieving a LDL-C level of 1.8 to 2.6 mmol/L or < 1.8 mmol/L versus > 2.6 mmol/L induced by statin initiation within one year on the risk of incident and recurrent fractures over five years.

Results: Among 165,242 people with hyperlipidaemia initiating statins (mean age 62.6 years, 51.1% female), the five-year risk of incident hip fracture was lower in the 1.8 to 2.6 mmol/L arm (0.53%) and in the < 1.8 mmol/L arm (0.52%) than the > 2.6 mmol/L LDL-C arm (0.65%). The corresponding hazard ratios (HRs) were 0.77 (95% CI 0.65 to 0.91) and 0.68 (95% CI 0.54 to 0.86), respectively. A similar decreased risk of recurrent hip fracture was observed for the 1.8 to 2.6 mmol/L arm (HR = 0.79, 95% CI 0.39 to 1.58) and < 1.8 mmol/L arm (HR = 0.32, 95% CI 0.15 to 0.66), respectively. Additionally, lowering LDL-C levels reduced the risks of composite fracture and major osteoporotic fracture.

Conclusion: In this population-based cohort study, LDL-C lowering was associated with a decreased risk of fracture in individuals with hyperlipidaemia. This decreased risk appeared to be associated with the extent of LDL-C lowering, suggesting that the therapeutic paradigm of 'lower is better' could be advantageous for fracture prevention in individuals with hyperlipidaemia.

Aims: Periprosthetic joint infection (PJI) is known to disrupt bone metabolism. Unlike lipopolysaccharide (LPS) from Gram-negative bacteria (GNB), lipoteichoic acid (LTA) from Gram-positive cocci (GPC) induces minimal osteoclast activation and bone resorption. Clinically, patients with Gram-positive bacterial component-associated PJI (GPC-PJI) exhibit less osteolytic activity than those with Gram-negative bacterial PJI (GNB-PJI), suggesting a milder disruption of bone homeostasis. In this study, we identified elevated levels of chemokine (C-X-C motif) ligand 5 (CXCL5) in the synovial fluid (SF) of GPC-PJI patients and investigated its regulatory role in osteoclast signalling and bone remodelling. A murine bone loss model was employed to assess its in vivo function.

Methods: SF samples from patients with PJI and aseptic loosening (AL) were analyzed using cytokine protein arrays and enzyme-linked immunosorbent assay (ELISA) to compare CXCL5 expression in the AL, GPC-PJI, and GNB-PJI groups. In vitro, MC3T3-E1 osteoblasts were used to examine CXCL5 induction following LTA stimulation, while RAW264.7 macrophages were used to evaluate the effects of CXCL5 on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation. In vivo, a mouse model received intra-articular LTA and intraperitoneal CXCL5 neutralizing antibody to investigate the role of CXCL5 in maintaining bone integrity under infectious conditions.

Results: CXCL5 was significantly upregulated in PJI patients, particularly in GPC-PJI cases. LTA stimulation increased CXCL5 secretion from osteoblasts in a dose-dependent manner. Functionally, CXCL5 inhibited osteoclast formation and reduced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. Kinase profiling revealed that CXCL5 suppressed osteoclastogenesis via PLCγ2 phosphorylation and c-Fos downregulation. In vivo, CXCL5 neutralization exacerbated LTA-induced bone loss.

Conclusion: CXCL5 is highly expressed in GPC-PJI and protects bone by inhibiting osteoclast differentiation through PLCγ2 and c-Fos signalling. In vivo evidence confirms its key role in preserving bone homeostasis during Gram-positive bacterial infection.

Aims: Acetabular bone defects pose a common challenge in revision total hip arthroplasty (THA). Our team has applied screw-supported prostheses to the revision of severe acetabular defects and achieved good early clinical results. However, in one of our cases, loosening of the screw-cup connection occurred five months after surgery. Therefore, we investigated the mechanical characteristics and weak points of this prosthesis system through finite element analysis (FEA) and mechanical testing, and proposed improvement strategies.

Methods: A screw-supported prosthesis used in clinical practice was modelled, and FEA was performed to obtain its displacement and von Mises stress distribution under gait loading. Emphasis was placed on the stresses at the screw-cup connection to analyze the failure mechanism. Mechanical compression tests were subsequently performed on the prosthesis, and the failure mode of the prosthesis verified the results of the FEA.

Results: FEA identified the posterior iliac and pubic locking connections as weak points prone to fatigue failure. Mechanical tests confirmed that the locking connection failed under 2,500 to 3,000 N loads. The improved sleeve connection enhanced connection strength and reduced failure risk.

Conclusion: The screw-supported prosthesis shows potential for severe acetabular defects, but the screw-cup connection remains a vulnerable site. Enhanced connection designs (e.g. sleeve connection) and bone grafting effectively mitigate failure risk.

Aims: Salmon calcitonin (CT) has been shown to have antiresorptive and chondroprotective effects, and several clinical trials have reported beneficial effects of salmon CT treatment in patients with knee osteoarthritis (OA). The objective of the present study is to investigate the role of endogenous CT-mediated signalling in OA.

Methods: Calcitonin receptor (CTR)-deficient mice and wild-type (WT) littermate controls were subjected to experimental post-traumatic OA (ptOA) by anterior cruciate ligament transection (ACLT). Radiological and histomorphometric outcome measurements in WT and CTR-deficient mice with ACLT were performed at early (4 weeks) and late (8 weeks) stages after ptOA induction. Expression of CTR on messenger RNA (mRNA) and protein level in sham and ACLT knees of WT mice were measured by gene expression analysis and immunofluorescence, respectively.

Results: In WT mice, Calcr mRNA was progressively induced in ptOA knees, and CTR protein was abundantly expressed in articular cartilage and subchondral bone (SB) in diseased joints. CTR^-/- mice displayed decreased osteophyte formation compared to WT mice, while cartilage deterioration, pathological SB alterations, and synovial inflammation were not affected by CTR deficiency. In line with this, bone resorption, cartilage, and inflammatory markers were unaltered between WT and CTR-deficient mice, while bone formation parameters were increased only in WT ptOA knees on gene expression level four weeks after surgery.

Conclusion: Although CTR is highly expressed in articular cartilage and SB and promotes osteophyte formation, endogenous CTR signalling does not affect cartilage degeneration and SB pathologies in murine ptOA.

Aims: The objective of this research was to assess the diffusion tensor imaging (DTI) parameters of deep cervical muscles in patients diagnosed with degenerative cervical myelopathy (DCM) before and after surgery at different follow-up stages, and to analyze their relationship with functional scores.

Methods: This study involved 30 patients with DCM who underwent cervical laminoplasty. DTI imaging and clinical assessments were performed preoperatively as well as at three-month and six-month follow-up. DTI parameters (fractional anisotropy (FA); mean diffusivity (MD); radial diffusivity (RD); and axial diffusivity (AD)) of cervical paraspinal muscles (multifidus and semispinalis cervicis) were measured, and mean values were calculated. Preoperative and postoperative changes in DTI parameters were analyzed using the Friedman test. Spearman correlation and linear regression analyses was conducted to assess the relationship between preoperative cervical paraspinal muscle DTI measurements and changes in modified Japanese Orthopedic Association (mJOA) scores and visual analogue scale (VAS) at preoperative and three-month and six-month follow-up. Multivariate logistic regression analysis was performed to assess the relationship between recovery rates of mJOA and VAS and changes of DTI metrics.

Results: Preoperative paraspinal muscle FA is associated with preoperative mJOA scores (r = 0.372, p = 0.043). Preoperative paraspinal muscle FA significantly correlated with VAS change at three-month (r = -0.461, p = 0.010) and six-month follow-up (r = -0.477, p = 0.008), and also correlated with mJOA recovery rate at six-month follow-up (r = 0.368, p = 0.045). Higher preoperative paraspinal muscle FA was a significant predictor of decreased VAS scores at three-month and six-month follow-up (β = -0.411, p = 0.024; β = -0.385, p = 0.035) and increased mJOA scores at six-month follow-up (β = 0.401, p = 0.028). Changes in FA (p = 0.033, OR 1.05 (95% CI 1.01 to 1.11)) and RD (p = 0.028, OR 1.27 (95% CI (1.03 to 1.58)) at six months' follow-up may be variables influencing the VAS change.

Conclusion: In DCM patients, changes in DTI parameters from preoperative to postoperative follow-up stages can indicate paraspinal muscle recovery after cervical surgery. DTI examination before surgery can predict patient recovery outcomes.