Journal of Orthopaedic Research®最新文献

This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with 0.25 ng LPS in the intercarpal joints of seven healthy Shetland ponies. The ponies were subsequently treated with either 6 mg liraglutide or a placebo as a paired control in each joint. The impact of liraglutide on biomarkers associated with inflammation (including white blood cell count, total protein, CCL2, and bradykinin) and cartilage metabolism (such as glycosaminoglycans, general matrix metalloproteinase activity, carboxypropeptide type II collagen, and collagen-cleavage neoepitope of type II collagen) was assessed across serial synovial fluid samples. Liraglutide was found to have an anti-inflammatory effect by reducing CCL2 concentrations in culture media of whole blood, PBMCs, chondrocytes, and synoviocytes. In contrast, no significant differences in synovial fluid inflammatory nor cartilage metabolism biomarker levels were found between joints treated with LPS and 6 mg liraglutide, versus LPS and placebo. In conclusion, liraglutide demonstrates the potential to attenuate inflammatory processes in joint cells. Additional research is necessary to validate its efficacy within the complex milieu of an inflamed joint.

Assessing the bone condition in patients with spinal disease is clinically valuable. However, evaluating bone strength in the presence of spine degenerative changes is challenging. Quantitative computed tomography (QCT) and finite element analysis (FEA) have been proposed as methods for more accurate bone quality assessment. This study investigates the relationship between bone strength predicted by FEA and other relevant biological parameters. This retrospective cross-sectional study included 127 patients with spinal disease who underwent preoperative CT scans between 2014 and 2020. Baseline patient characteristics, volumetric bone mineral density (vBMD) measured by QCT, and vertebral bone strength predicted by FEA were collected. The degree of degeneration was evaluated by classifying osteophyte formation, disc height narrowing, vertebral sclerosis, and spondylolisthesis into a grading scale ranging from 0 to 2. Multiple linear regression analysis was conducted to assess the effect of each factor on bone strength predicted by FEA. Of 127 patients, 120 patients (median age was 62 years) were included. The median vBMD and vertebral strength were 114.3 mg/cm³ and 7892.9 N, respectively. After adjusting for age, sex, body mass index, smoking status, diabetes mellitus, vBMD, and degenerative changes, multiple linear regression analysis revealed that sex, vBMD, and degree of degeneration independently increased the vertebral strength measured by FEA. This study suggests that in patients with spinal disease, vertebral bone strength is affected not only by sex and bone mineral density but also by degenerative changes. Thus, bone strength could be predicted more accurately in patients with spinal disease using FEA.

The objective of this study was to evaluate scaphoid, lunate and capitate kinematics after disruption to the primary and secondary scapholunate ligamentous stabilizers, and to assess the effectiveness of scapholunate ligament reconstruction in restoring carpal kinematics post-operatively. Seven upper extremities were harvested, and the scapholunate interosseous ligament (SLIL) was divided. Specimens were mounted onto a computer-controlled dynamic wrist simulator, and simulations of flexion-extension, radial-ulnar deviation, and dart-thrower's motion were undertaken by simulated force application to the wrist tendons. Three-dimensional kinematics of the scaphoid, lunate and capitate were measured using bi-plane X-ray fluoroscopy in the native and ligament deficient state. The SLIL was then reconstructed by either dorsal transarticular loop tenodesis (DTLT), or by the three-ligament tenodesis (3LT) technique, and re-evaluated. SLIL deficiency resulted in significant differences in carpal kinematics compared to that in the healthy wrist across all wrist motions (p < 0.05). The DTLT procedure corrected increased scaphoid ulnar deviation and pronation in the SLIL deficient wrist, but did not significantly improve scaphoid flexion or volar translation of the scaphoid. The 3LT reconstructive technique restored scaphoid flexion and ulnar deviation but did not correct pronation, the increased lunate extension, nor the volar and ulnar translation observed in the ligament deficient wrist. Three-dimensional scaphoid, lunate and capitate motion depends on SLIL integrity, with tears to this ligament resulting in pathological kinematics, which may be partially mitigated with DTLT and 3LT surgical reconstruction. These findings suggest that this surgical reconstruction of the SLIL may not mitigate long-term degenerative joint conditions at the wrist.

Endothelial progenitor cells (EPCs) have proven to be a highly effective cell therapy for critical-sized bone defects. Cryopreservation can enable long-term storage of EPCs, allowing their immediate availability on demand. This study compares the therapeutic potential of EPCs before and after cryopreservation in a small animal critical-sized bone defect model. Five-millimeter segmental defects were created in the right femora of Fischer 344 rats, followed by stabilization with a miniplate and screws. The animals received 2 × 10⁶ fresh EPCs (n = 7) or 2 × 10⁶ cryopreserved EPCs (n = 9) delivered on a gelatin scaffold. Cryopreserved EPCs were stored for 7 days at -80°C prior to thawing and loading onto the gelatin scaffold. Biweekly radiographs were taken until the animals were euthanized 10 weeks after surgery. The operated femora were then evaluated using microscopic-computed tomography (micro-CT) and biomechanical testing. All animals treated with fresh (n = 7/7) or cryopreserved (n = 9/9) EPCs achieved radiographic union at 10 weeks. Animals treated with fresh EPCs had statistically significant higher radiographic scores at 2 weeks (p < 0.05) but showed no statistically significant differences thereafter (p > 0.05). Micro-CT analysis showed no statistically significant differences between the groups in bone volume (BV) or BV normalized to total volume (p > 0.05), with excellent bone formation in both groups. Finally, there were no differences in biomechanical outcomes between the groups (p > 0.05). These results demonstrate that cryopreserved EPCs are highly effective and equivalent to fresh EPCs for healing critical-sized bone defects in a rat model of nonunion.

The goal of medial open-wedge high tibial osteotomy (MOW-HTO) is to redistribute load by realigning the lower limb. This surgery is indicated for mild to moderate medial compartment osteoarthritis with varus deformity in cases unresponsive to conservative treatment. Procedures for accompanying cartilage lesions, such as multiple drilling on the medial femoral condyle (MFC), are often performed simultaneously, potentially affecting bone metabolism along with load redistribution and union progression. This study assessed changes in bone metabolism following MOW-HTO. Two-year follow-up data were collected from 51 knees undergoing MOW-HTO between March 2019 and December 2020. Single-photon emission computed tomography and conventional CT (SPECT/CT) were performed on postoperative Day 1, 3 months, 1 year, and 2 years. Maximum standardized uptake value (SUVmax) was measured in each compartment and the osteotomy gap. At 1 year postoperatively, SUVmax decreased in the medial femur and tibia zones (p < 0.001). SUVmax decreased in the lateral osteotomy gap zones at 1 year (p = 0.001 anterior; p = 0.002 posterior), while medial zones showed a sustained increase. At the posteromedial zone, SUVmax decreased at 2 years (p = 0.012). Subjects were divided into two groups: those with MFC drilling (group one) and those without (group two). SUVmax was higher in group one throughout the 2 years (p < 0.001). Unloading effects were notable in the medial compartment. MFC drilling increased SUVmax, creating different patterns between groups. SUVmax decrease in the osteotomy gap occurred earlier in the lateral zone.

The role of the infrapatellar fat pad (IPFP) in knee osteoarthritis is not understood. This study aimed to identify relationships between MRI-based signal abnormalities in the IPFP and measures of structural pathology and symptom severity in PFJOA, as well as investigate the influence of obesity and sex on these relationships. Seventy participants (ages 28-80) with isolated PFJOA underwent bilateral knee MRI scan acquisitions and completed the Knee Injury and Osteoarthritis Outcome Score (KOOS). MR images were scored for abnormal IPFP area and signal intensity, joint effusion, synovial proliferation, and patellar and trochlear cartilage damage. Repeated measures correlations were performed to assess associations between abnormal area and signal of IPFP and PFJOA pathology and KOOS, respectively. Associations were interrogated across weight-based groups based on BMI and sex-based groups. Between abnormal IPFP and PFJOA pathology, we observed no significant associations. Between abnormal IPFP and patient-reported outcomes, we observed weak to moderate significant negative associations between the size of the abnormal IPFP area and all KOOS subscales. In a sex-based analysis of IPFP and KOOS associations, we observed significant moderate negative correlations between IPFP and KOOS scores across all subcategories in female participants. In male participants, abnormal IPFP was not associated with KOOS scores. The IPFP is significantly related to PFJOA patient-reported pain and function, and this correlation is stronger in high-risk OA groups.

Previous studies suggest a relationship between femoroacetabular impingement (FAI) and femoral neck stress fractures (FNSF), due to pathologic biomechanics in the setting of femoral head abutment (cam morphology) and/or acetabular overcoverage (pincer morphology). The purpose of this study is to evaluate the association between cam or pincer morphology and FNSF, compared to a control group of patients without hip pain. A retrospective review of the electronic medical record at a single institution was queried for patients with FNSF over a 10-year time period from January 2011-2021. These patients were compared to a control group with diagnostic radiographs and a chief complaint that was not hip pain presenting to the institution's emergency department. Hip morphology was evaluated radiographically. A multivariate logistic regression was used to investigate an association between FNSF and cam or pincer morphology. Eighty-three patients with FNSF and a mean age of 38.6 years were compared to 55 healthy controls with a mean age of 35.8 years. Patients in the FNSF group were more often female, white, and had lower BMI. These patients were also more likely to have associated cam morphology (p = 0.010). Binary logistic regression demonstrated a statistically significant independent association between both cam (OR 5.2, p = 0.01) and pincer (OR 4.6, p = 0.022) morphology with FNSF when controlling for demographic variables. Black race and higher BMI were protective factors for FNSF (OR 0.09, OR 0.84, p < 0.01). In summary, radiographic cam morphology, superolateral acetabular overcoverage, female sex, and lower BMI are risk factors for sustaining FNSF, while the black race was found to be protective.

Flexible flatfoot is common among school-age children and significantly affects walking efficiency, balance stability, and joint-movement coordination in children. The demands on the skeletal structure and muscle function are increased during running; however, the impact of a flexible flatfoot on children's running capabilities is unclear. In this study, we aimed to investigate the effects of flexible flatfoot on the running function of school-age children. Participants with flat feet (n = 28) and typical feet (n = 27) ran on a flat surface at their chosen maximum pace. At the same time, the kinematic and dynamic parameters of their lower limb joints were monitored. A two-sample statistical analysis assessed the differences in the lower limbs' three-dimensional kinematic and dynamic parameters during running. The findings revealed a significant reduction in running velocity, stride length, and frequency, and an increased proportion in the support phase (p < 0.05) in children with flexible flat feet. The navicular drop time decreased, whereas the dynamic navicular drop height increased (p < 0.05). A notable decrease in the maximum plantar flexion and eversion torque, power, and power absorption of the ankle joint was observed (p < 0.01). Furthermore, the maximum flexion torque of the knee and hip joints and hip joint power absorption decreased (p < 0.05). The peak ground reaction force in the anteroposterior directions was reduced (p < 0.01). These results indicate that flexible flatfoot can impair the running efficiency of school-age children and lead to diminished motor stability and reduced propulsive and braking capabilities.

Compression neuropathy is a prevalent medical condition, including common types such as carpal tunnel syndrome, cubital tunnel syndrome, sciatica, and many others. While the neurological consequences are well understood, the effects on bone properties and the potential downstream impact on fracture risk remain less clear. This study aimed to assess the influence of compressive neuropathy on bone properties using a rabbit model of sciatic nerve compression. We hypothesized that compressive neuropathy could adversely alter bone properties. Five New Zealand white rabbits underwent surgery to induce perineural scarring in the sciatic nerve, with the contralateral limb serving as a sham control. Bone mineral density (BMD), mechanical strength, and bone signaling proteins were evaluated through microcomputed tomography (μCT), four-point bending tests, and ELISA assays, respectively. Sciatic nerve histology was analyzed using VEGF and Nissl staining to assess axon and Schwann cell densities and quantified using image analysis software. The results showed no significant differences in BMD, biomechanical properties, or key bone signaling proteins (OPG and RANKL) between the affected and control tibias. These findings suggest that compression neuropathy does not significantly impact bone properties in the rabbit model.

Effective surgical planning is crucial for maximizing patient outcomes following complex orthopedic procedures such as proximal femoral osteotomy. In silico simulations can be used to assess how surgical variations in proximal femur geometry, such as femur neck-shaft and anteversion angles, affect postoperative system mechanics. This study investigated the sensitivity of femur mechanics to postoperative neck-shaft angles, anteversion angles, and osteotomy contact areas using patient-specific finite element analysis informed by neuromusculoskeletal models. A sequential neuromusculoskeletal modeling and finite element analysis pipeline was used to simulate postoperative mechanics in three pediatric patients with varying demographic and anatomic features. Nine surgical configurations derived from permutations of the clinical envelope of neck-shaft angles and anteversion angles were simulated for the stance phase of gait. The outcome mechanics assessed were peak von Mises stresses on the bone-implant contact surfaces as well as interfragmentary movement and strain on the osteotomy location. Peak von Mises stress and interfragmentary movement and strain were on average 38% more sensitive to surgical variation in neck-shaft angle compared to anteversion angle. A significant negative correlation was detected between contact area and interfragmentary movement (r = -0.90, p < 0.0001) and strain (r = -0.45, p = 0.017). Overall findings suggest neck-shaft angle significantly influences postoperative femur mechanics and highlight the importance of maximizing contact area to limit interfragmentary motion and foster an optimal mechanical environment for bone healing and callus formation following proximal femoral osteotomy. Between-patient variation in sensitivity to proximal femoral geometry reinforced the importance of patient-specific surgical planning.