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PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent an effective strategy for reducing cardiovascular disease risk. Yet, PCSK9’s impact on osteoporosis remains unclear. Hence, we employed Mendelian randomization (MR) analysis for examining PCSK9 inhibitor effects on osteoporosis.MethodsSingle nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis.ResultsThe meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I2, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions.ConclusionPCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.

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Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study

ObjectiveIn chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI.MethodsAll the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed.ResultsA total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535).ConclusionThe degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

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Association between Dietary total antioxidant capacity and knee osteoarthritis: a case-control study in the Iranian Population

AimKnee osteoarthritis (KOA) is a prevalent chronic condition associated with significant pain, disability, and healthcare costs, particularly among the elderly population. Despite the considerable burden of KOA, effective treatment options for managing the condition’s underlying causes remain limited. This case-control study aims to investigate the relationship between dietary total antioxidant capacity (DTAC) and knee osteoarthritis.MethodsThis case-control study was conducted on 105 patients with confirmed KOA and 210 controls. KOA was diagnosed based on the American College of Rheumatology criteria. Dietary total antioxidant capacity (DTAC) was calculated based on the ferric-reducing antioxidant power method.ResultsThe mean age and BMI of the participants were 53.6 ± 8.8 years old and 27.3 ± 2.7 kg/m2, respectively. The study participant’s DTAC score ranged from 3.56 to 25.32 with a mean and SD of 12.46 ± 5.12. In the crude model, individuals in the highest quartile of DTAC score had 71% lower odds of having knee osteoarthritis compared to those in the first quartile (OR: 0.29, 95%CI: 0.15 to 0.58, P-trend < 0.001). These associations remained significant after adjustment for potential confounders including age, sex, energy intake, family history of osteoarthritis, vitamin D and calcium use, physical activity level, cigarette smoking and BMI. Although the odds of having knee osteoarthritis decreased with increasing quartiles of DTAC in both sexes, this relationship was stronger among males than females.ConclusionThe results of this study showed that there was an inverse correlation between DTAC and KOA among the Iranian patients with KOA.

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Deep learning approach to femoral AVN detection in digital radiography: differentiating patients and pre-collapse stages

ObjectiveThis study aimed to evaluate a new deep-learning model for diagnosing avascular necrosis of the femoral head (AVNFH) by analyzing pelvic anteroposterior digital radiography.MethodsThe study sample included 1167 hips. The radiographs were independently classified into 6 stages by a radiologist using their simultaneous MRIs. After that, the radiographs were given to train and test the deep learning models of the project including SVM and ANFIS layer using the Python programming language and TensorFlow library. In the last step, the test set of hip radiographs was provided to two independent radiologists with different work experiences to compare their diagnosis performance to the deep learning models’ performance using the F1 score and Mcnemar test analysis.ResultsThe performance of SVM for AVNFH detection (AUC = 82.88%) was slightly higher than less experienced radiologists (79.68%) and slightly lower than experienced radiologists (88.4%) without reaching significance (p-value > 0.05). Evaluation of the performance of SVM for pre-collapse AVNFH detection with an AUC of 73.58% showed significantly higher performance than less experienced radiologists (AUC = 60.70%, p-value < 0.001). On the other hand, no significant difference is noted between experienced radiologists and SVM for pre-collapse detection. ANFIS algorithm for AVNFH detection with an AUC of 86.60% showed significantly higher performance than less experienced radiologists (AUC = 79.68%, p-value = 0.04). Although reaching less performance compared to experienced radiologists statistically not significant (AUC = 88.40%, p-value = 0.20).ConclusionsOur study has shed light on the remarkable capabilities of SVM and ANFIS as diagnostic tools for AVNFH detection in radiography. Their ability to achieve high accuracy with remarkable efficiency makes them promising candidates for early detection and intervention, ultimately contributing to improved patient outcomes.

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Evaluation of the clinical efficacy of using an inverted triangular cannulated compression screw in combination with positive or negative buttress reduction for the healing of femoral neck fractures

ObjectiveWe aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures.MethodsBetween October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint.ResultsAll patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score.ConclusionThe success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures.

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Development of a novel approach for restoration of the meniscus using silk-elastin in a rabbit meniscus injury model

BackgroundLimited healing potential of the meniscus remains a burden for the successful repair of meniscus injuries in the orthopaedic fields. Silk-elastin (SE) is a novel recombinant protein with favorable properties for wound healing. This proof-of-concept study aimed to investigate the therapeutic effect of silk-elastin in a rabbit meniscal defect model.MethodsA migration assay using rabbit meniscus and synovial cells with various concentrations of SE in a culture medium was conducted to investigate the mechanism of meniscal healing by SE. Additionally, cylindrical defects with a 1.5 mm diameter were created at the anterior horn of the medial meniscus of rabbits. The animals were divided into three groups: 1) the Blank group; defect only, 2) the Col I group; implantation of type I atelocollagen sponge, and 3) the SE group; implantation of SE (150 mg/ml) sponge. Whole medial menisci were harvested at 4, 8, 12, and 24 weeks after surgery. Histological analyses including immunohistochemical staining were performed to assess meniscal healing.ResultsIn vitro study, Migration assay demonstrated a significantly higher number of migrated cells only in synovial cells. Especially, the SE concentration of 10 µg/mL demonstrated the highest number of migrated cells compared with other concentrations. In vivo study, the SE group exhibited significantly higher Ishida scores than other groups at all time points. Furthermore, the SE group showed higher synovial coverage scores than the Col I group at 4 and 8 weeks. Immunohistochemical staining demonstrated higher type II collagen staining in the SE group compared to other groups at 12 weeks. Implanted SE was efficiently replaced by safranin-O staining positive tissue within 8 weeks.ConclusionsSE could effectively repair a meniscal defect by inducing coverage of synovial cells. SE has the potential to be a useful material for meniscal repair.

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Effect of dorsal capsular imbrication on intraoperative DRUJ instability following arthroscopic TFCC repair surgery

BackgroundTo assess the clinical outcomes and identify the ideal indication for implementing dorsal distal radioulnar joint (DRUJ) capsular imbrication after triangular fibrocartilage complex (TFCC) repair in cases of DRUJ instability.MethodsWe conducted a retrospective study on patients who underwent arthroscopic TFCC repair between 2016 and 2021. Inclusion criteria comprised a symptomatic ulna fovea sign for over 6 months and dorsal DRUJ subluxation on magnetic resonance imaging. A total of 225 patients were divided into two groups: Group 1 (135 cases) with a negative ballottement test after “Cross-form TFCC repair” (CR) and Group 2 (90 cases) with a positive ballottement test after “Cross-form TFCC repair” and augmented DRUJ stability through dorsal DRUJ capsular imbrication (CR + DCI). Pain visual analog scale score (VAS), grip strength, modified Mayo Wrist Score (MMWS), wrist range of motion (ROM), and patient-reported outcomes (PROMs) were assessed for a minimum of 3 years postoperatively.ResultsBoth groups showed significant improvements in pain VAS score, grip strength, wrist ROM, MMWS, and PROMs between the preoperative and postoperative periods (all P < 0.05). Recurrent DRUJ instability occurred in 3.7% and 1.1% of patients in the “CR” and “CR + DCI” groups, respectively, with a significant difference. Despite the “CR + DCI” group initially exhibiting inferior ROM compared with the “CR” group, subsequently, no significant difference was noted between them.ConclusionsDorsal DRUJ capsular imbrication effectively reduces postoperative DRUJ instability rates, enhances grip strength, and maintains wrist ROM in patients with a positive intra-operative ballottement test after arthroscopic TFCC repair.

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Changes in the anteroposterior position of the femur relative to the tibia impact patient satisfaction in total knee arthroplasty

BackgroundIn this study, we aimed to investigate the preoperative and postoperative anteroposterior position (AP) of the femur relative to the tibia in total knee arthroplasty (TKA) and assess the influence of change in the AP position on clinical outcomes.MethodsWe evaluated 49 knees that underwent bi-cruciate-substituted TKA using a navigation system. The preoperative and postoperative AP position of the femur relative to the tibia at maximum extension, 15°, 30°, 45°, 60°, 90°, 105°, and 120° and maximum flexion angles were calculated. The 2011 Knee Society Score was evaluated preoperatively and 1 year postoperatively. The Wilcoxon signed rank and Spearman’s rank correlation tests were performed, with statistical significance set at P < 0.05.ResultsThe postoperative AP position was significantly correlated with the preoperative AP position at each measured angle. The postoperative AP positions were statistically more anterior than those preoperatively. Furthermore, the changes in the AP position after TKA negatively correlated with the symptom (P = 0.027 at 30°, P = 0.0018 at 45°, P = 0.0003 at 60°, P = 0.01 at 90°, and P = 0.028 at 105°) and patient satisfaction (P = 0.018 at 60° and P = 0.009 at 90°) scores at 1 year postoperatively.ConclusionThe postoperative AP position of the femur relative to the tibia was strongly influenced by the preoperative those in TKA. Postoperative anterior deviation of the femur relative to the tibia from mid-flexion to deep flexion could worsen clinical outcomes.

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Diffusion-tensor magnetic resonance imaging as a non-invasive assessment of extracellular matrix remodeling in lumbar paravertebral muscles of rats with sarcopenia

BackgroundExtracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology.MethodsTwenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers.ResultsThe cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were − 0.71, -0.94, -0.85, and − 0.88, respectively (p < 0.05 for all).ConclusionsThe fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia.

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