Journal of Orthopaedic Research®最新文献

Tendinopathy is a complex, painful condition that affects up to 5% of the general population in their lifetime. Antibiotic treatment with fluoroquinolones has been associated with the onset of tendinopathy and tendon rupture. The mechanisms behind fluoroquinolone induced tendinopathy remain unclear. To probe activation of potentially causative pathways, we treated juvenile mice with ciprofloxacin in drinking water for 4 weeks and performed RNA sequencing on tail tendons. We discovered that ciprofloxacin-treated mice had upregulated genes relating to nerve development. Additionally, treated mice showed downregulation of genes associated with extracellular matrix (ECM) processes. We further explored ECM changes using histological and mechanical testing methods on patellar tendons. We found that ciprofloxacin treatment led to altered cell morphology and proteoglycan density. These changes translated to a decrease in mechanical properties of the patellar tendons. Furthermore, ciprofloxacin-treated mice had a higher percentage of apoptotic cells, and we confirmed increased presence of nerve cells (Plexin B1⁺) in the patellar tendons compared to controls. Taken together, we showed that ciprofloxacin treatment in juvenile mice induces structural and biological phenotypes commonly associated with fluoroquinolone-induced tendinopathy and identify the axis of pathological neural activation as a promising area for further exploration. Clinical significance: Oral administration of ciprofloxacin in mice presents a clinically relevant model for studying mechanisms of tendinopathy in humans.

Patients with idiopathic carpal tunnel syndrome (CTS) exhibit impaired mitochondrial function in the subsynovial connective tissue (SSCT) of the carpal tunnel. We hypothesized that Imeglimin, a compound known to enhance mitochondrial function, may improve mitochondrial activity in SSCT from these patients. This study aimed to evaluate the effects of Imeglimin on mitochondrial function in SSCT-derived cells obtained from patients with idiopathic CTS. SSCT samples were collected from 15 patients (mean age: 67.5  ±  9.7 years) who underwent carpal tunnel release surgery between April 2022 and March 2024. The cells were cultured under control conditions (Dulbecco's Modified Eagle Medium alone) or with 100 µM Imeglimin for 24 h. Mitochondrial function was assessed using multiple assays, including cell proliferation, superoxide dismutase (SOD) activity, apoptosis rate, mitochondrial volume, membrane potential, reactive oxygen species (ROS) production, gene expression related to mitochondrial biogenesis and antioxidant capacity, mitochondrial permeability transition pore opening, and ultrastructure by transmission electron microscopy. Statistical analyses were performed using the Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, and Fisher's protected least significant difference test, with p  <  0.05 considered significant. Compared with the control group, the Imeglimin-treated group showed significantly increased cell proliferation, SOD activity, mitochondrial membrane potential, mitochondrial volume, cristae density, and expression of genes related to mitochondrial biogenesis and antioxidant defense. Apoptosis and mitochondrial ROS production were significantly reduced (p <  0.05). These findings suggest that Imeglimin may enhance mitochondrial function in SSCT-derived cells from patients with idiopathic CTS, offering a potential therapeutic strategy for mitochondrial dysfunction in CTS.

The goal of this radiomic analysis is to quantify the sensitivity of radiomic features on computed tomography (CT) image pre-processing parameters and use machine learning (ML) techniques to identify the radiomic features that are highly predictive of shoulder arthroplasty outcomes. An ML framework auto-segmented 3D masks of the deltoid muscle and scapula bone from pre-operative CT images of 1949 primary anatomic total shoulder arthroplasty (aTSA)/reverse total shoulder arthroplasty (rTSA) patients. Radiomic features were extracted after various image pre-processing protocols and assessed for reproducibility. The radiomic features deemed robust to image pre-processing were used to train ML predictive outcomes models. Feature importance data were rank-ordered to identify the radiomic features that were highly predictive of pain, motion, and function before and after aTSA/rTSA. A sensitivity analysis identified 37 deltoid muscle and 38 scapular bone radiomic features that were robust, reproducible, and unique across image pre-processing parameters. The most predictive deltoid muscle radiomic measurements were normalized volume, elongation, flatness, fat percentage, sphericity, and max 2D diameter column. The most predictive scapular bone radiomic measurements were flatness, sphericity, elongation, max 2D diameter column, and max 2D diameter slice. Radiomic data of the deltoid and scapula were highly predictive of pain, motion, and function before and after aTSA and rTSA. Radiomic data were more predictive than patient comorbidities, diagnosis, and implant type/size data, but less predictive than pre-operative active range of motion measurements and patient reported outcome measures, 3D measurements from planning software, or patient demographic data. Future work is required to clinically validate these radiomic features before they can be deployed in clinical decision support tools. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Outcome Study.

Total knee arthroplasty (TKA) represents the gold standard for relieving pain and restoring function in patients with end-stage knee osteoarthritis. Soft-tissue balancing is critical to achieving successful outcomes. One of the factors that contribute to successful soft-tissue management relates to tibial insert thickness, an intraoperative surgical decision based on surgeon experience and preference. This study investigates the relationship between knee joint laxity curves and tibial insert thickness selection in tibia-first TKA and explores predictive modeling to support intraoperative decision making. Data from 1661 tibia-first TKA cases performed by 11 surgeons were used to develop surgeon-dependent and surgeon-independent models. Surgeon-dependent models are personalized to individual surgeons, leveraging data specific to each surgeon. While surgeon-independent models are developed utilizing data from seven expert surgeons (> 70 cases each) to provide generalized recommendations. Three supervised machine learning (ML) algorithms logistic regression (LR), random forest (RF), and XGBoost (XGB) were employed with feature selection methods: correlation-based feature selection (CFS), recursive features elimination (RFE), and Shapley additive explanations (SHAP). The best surgeon-dependent model achieved a mean exact prediction accuracy of 58.3%, mean prediction within 1 mm accuracy of 73%, and mean prediction within 2 mm accuracy of 93.1%. The top-performing surgeon-independent model demonstrated improved accuracy, with a mean exact prediction accuracy of 61.3%, mean prediction within 1 mm accuracy of 73.3%, and mean prediction within 2 mm accuracy of 94.2%. These findings suggest that ML models can assist in standardizing tibial insert thickness selection, potentially reducing variability and improving intraoperative decision-making in TKA.

End-stage arthritis of the hip, knee, or ankle leads to differential gait adaptations, but the differences in gait stability remain poorly understood. This study examined whether dynamic gait stability differed between patients with end-stage hip arthritis (HA), knee arthritis (KA) and ankle arthritis (AA), and matched healthy controls (HC). Anteroposterior (AP) and mediolateral (ML) Margin of Stability (MoS) were determined at heel strike, contralateral toe-off, and midstance during overground walking in 30 HA, 20 KA, 30 AA, and 30 HC participants. Data was analyzed using linear mixed-effects models with gait speed included as a fixed effect and participant as a random effect. A significant interaction was found between group (HA, KA, AA, HC) and limb (arthritic, non-arthritic) for every MoS variable (p < 0.001). HA and AA exhibited greater arthritic limb ML MoS during single support (p < 0.001) and smaller non-arthritic limb AP MoS at heel-strike (p < 0.033) when compared to HC. HA exhibited the least conservative non-arthritic limb AP MoS at midstance (p = 0.044), suggesting reduced AP stability. KA showed the smallest non-arthritic limb ML MoS at heel-strike (p < 0.022), indicating greater lateral instability. Within all patient groups (HA, KA, AA), ML stability was more conservative in the arthritic limb compared to the non-arthritic limb (p < 0.001). These findings suggest isolated lower extremity joint arthritis differentially impacts gait stability depending on the affected joint and limb, highlighting the need for targeted rehabilitation strategies to address stability deficits based on the joint impacted by arthritis.

Based on anecdotal observation of fatty infiltration (FI) of the opponens pollicis (OPP) muscle in patients with thumb carpometacarpal (CMC) Osteoarthritis (OA), we sought to examine the association of FI with CMC OA. We reviewed 747 consecutive 3 T wrist magnetic resonance imaging (MRI) studies for evidence of FI in the thenar muscles. This population was divided into two cohorts based on radiographic analysis: a cohort without thumb CMC OA (n = 440) and a second cohort with thumb CMC OA (n = 307), staged according to the Eaton-Littler classification. Statistical analysis using logistic regression was performed to investigate clinical factors associated with the presence of FI in the thenar muscles. FI was present in 133 patients with CMC OA (43.3%). FI, when present, was located only in the OPP. We found no OPP FI in the cohort without CMC OA (440 patients). Among patients with CMC OA, increasing age, male sex and advanced OA stage were significantly associated with the presence of OPP FI. OPP FI is a frequent finding in CMC OA. This FI could affect the biomechanical function of the OPP. In the future, we plan to analyze clinical outcomes in CMC OA patients with and without FI, and more focused in vivo studies of OPP function. OPP FI could potentially affect the function and the stability of the thumb CMC joint in patients with CMC OA. Orthopaedic Research Society. Journal of Orthopaedic Research® 00:00-00, 2026.

Total hip arthroplasty (THA) is estimated to exceed 500,000 procedures annually in the United States. Often after THA, deficits observed range from poor physical performance, muscle weakness and joint mechanics compensation, negatively impacting return to daily physical function. The direct anterior approach (DAA) is theorized to cause less gluteal muscle disruption, potentially leading to better physical function recovery compared to the posterolateral approach (PLA) post-THA. This study evaluated differences in physical function recovery in 93 participants who underwent a primary, unilateral THA with either a DAA (n = 68) or PLA (n = 25) approach. Outcomes were assessed preoperatively, 10- and 24-weeks post-THA. Physical function recovery was measured as 6-min walk test, Functional Gait Assessment, daily step count, muscle strength (hip abductor, knee extensor, knee flexor) and joint mechanics during walking and step negotiation. Repeated measures analysis of covariance models were used to estimate the effect of surgical approach on outcomes over time, adjusting for age, sex, preoperative body mass index and surgeon years of experience. Participants with DAA demonstrated greater 6-min walk distance 24-weeks post-THA and greater hip abductor strength 10-week post-THA compared to PLA. Participants with DAA also demonstrated subtle reductions in hip and trunk mechanics during walking and step negotiation compared to PLA post-THA. Statement of Clinical Significance: The DAA resulted in better recovery in 6-min walk distance (24-weeks), hip abductor strength (10-weeks) and joint mechanics (10- and 24-weeks) when compared with the PLA post-THA. This suggests the DAA demonstrated marginal improvement in physical recovery, despite both surgical approaches showing success.

This study investigated the factors that cause articular cartilage damage after subchondral curettage. Twenty-six male New Zealand White rabbits were divided into four groups: A (control), B (bone cementation post-curettage), C (phenol post-curettage), and D (phenol and bone cementation post-curettage). Each group had 13 knees treated similarly. The rabbits were monitored for 8 weeks postoperatively. A lateral subchondral bone window was created, after which the curettage procedure was performed. Serum cartilage oligomatrix protein (COMP) levels were analyzed before and after the procedure. At week eight, Magnetic Rezonance Imaging (MRI) was performed on both knees. Cartilage deterioration was assessed using OARSI cartilage. Fibrillation index and cartilage thickness were measured histopathologically. The lateral condyle cartilage thickness was lower than the medial thickness in all regions on the MRI. No significant differences were observed in the femoral condyle of the control group; however, differences were found in the other groups. Serum COMP levels increased at week 8 but were not significant, with no differences across the groups before (p = 0.507) or after (p = 0.199). The lateral condyle had a higher OARSI grade, stage, and total scores than the medial condyle (p < 0.001). Significant differences between the lateral and medial condyle in the OARSI scores were found between the phenol, cement, and phenol+cement groups (p = 0.014, p = 0.019, and p = 0.006, respectively). The lateral condyle showed a higher fibrillation index and lower cartilage thickness than the medial condyle (p < 0.001). Adjuvant therapy after curettage causes more subchondral cartilage damage. Changes in the subchondral bone microenvironment resulting from curettage and adjuvant therapies affect cartilage metabolism and contribute to osteoarthritis-related degradation.