骨科领域文献阅读汇编

A rate-limiting step in the prevention and early intervention of osteoporosis is identifying its asymptomatic onset. Accumulating evidence shows that sleep disorders are associated with an increased risk of osteoporosis. Given their early detectable and modifiable nature, integrating sleep disorder management into osteoporosis prevention and care pathways offers a novel approach for enhancing skeletal health. This expert consensus represents a collaborative effort by specialists in sleep medicine and orthopedics from across the world, integrating epidemiological, mechanistic, and interventional evidence to provide general guidance for prevention and clinical practice, and to foster multidisciplinary collaboration in the management of sleep disorders and osteoporosis.

The purpose of this study was to evaluate the association between systemic low bone mineral density (BMD) and subchondral insufficiency fracture (SIF) of the knee in women, and to explore whether this association is modified by radial meniscal tears. In this case-control study, women with and without MRI-confirmed SIF who had available dual-energy X-ray absorptiometry T-score measurements were included. Systemic BMD was categorized using T-scores. Multivariable logistic regression models with BMD as the exposure and SIF as the outcome, adjusting for age and body mass index were fitted. An exploratory stratified analysis to assess potential effect modification by meniscal radial tear status was also conducted. A total of 121 women with SIF (mean age, 69.1 ± 7.5 [standard deviation] years) and 124 controls (70.4 ± 8.3 [standard deviation] years) were analyzed. After adjustment, osteoporosis was associated with higher odds of SIF (odds ratio [OR], 2.29; 95% confidence interval [CI]: 1.03-5.09), whereas osteopenia (OR, 1.33; 95% CI: 0.69-2.55) showed no significant association. In exploratory stratified analysis to test for effect modification, there were no significant interactions between low BMD and radial root tears (P-interaction = 0.178). However, small strata likely limited the power to detect a significant effect modification, as evidenced by overlapping wide 95% CIs. Osteoporosis is associated with higher odds of SIF of the knee in women, while osteopenia is not.

Postmenopausal osteoporosis is driven by estrogen deficiency, while current therapies are limited by poor specificity and safety concerns. Here, inspired by the dietary use of soybean as a natural source of phytoestrogens, soybean-derived nanovesicles are identified as a bioinspired nanoestrogen platform enriched with estrogen-like bioactive components. These edible nanovesicles are produced via a scalable strategy with high yield and robust batch-to-batch consistency, ensuring quality controllability. They are efficiently internalized by cells and may involve estrogen receptor-mediated dual regulation of bone remodeling by promoting osteogenesis and inhibiting osteoclastogenesis, thereby restoring bone homeostasis. In vivo, they exhibit prolonged circulation and preferential bone accumulation, leading to effective bone regeneration. Importantly, systematic biosafety evaluations demonstrate excellent biocompatibility. These findings suggest that edible soybean-derived nanovesicles may serve as a quality-controllable nanoestrogen-like platform for osteoporosis intervention, while further mechanistic, safety, and translational studies are required before clinical application.

Osteoporotic fracture healing is trapped in a vicious cycle where multiple pathological factors, including persistent oxidative stress, inadequate vascular supply, and an imbalance bone remodeling process that favors resorption, combine to form a hostile niche for regeneration. The intricate interaction of these pathologies highlights the need to transform titanium implants from inert devices into active platforms for bone regeneration. In this study, a multifunctional coating where titanium dioxide nanotubes (TNT) are decorated with metal-organic networks (TNT@EZCA) is developed for coordinated regulation of pathological processes. The metal-organic network, composed of EGCG, Zn2 +, Ca2 +, and ALN, is engineered to orchestrate a pro-regenerative microenvironment that concurrently targets oxidative stress, angiogenesis, and bone homeostasis. In vitro studies confirm that the coating effectively scavenges reactive oxygen species, promotes endothelial cell functions, and re-establishes the balance between osteoblast and osteoclast. In an osteoporotic fracture model, TNT@EZCA significantly accelerates bone regeneration, improves bone microstructure and callus vascularization, and exerts a systemic osteoprotective effect. This study demonstrates that a multifunctional and integrated regulatory strategy effectively drives a systemic osteoprotective effect involving vascular network reconstruction and bone homeostasis restoration, offering a potential therapeutic strategy for improving the healing of osteoporotic fractures.

Osteoporosis is a chronic disease driven by an imbalance between bone-building osteoblasts and bone-resorbing osteoclasts, whose hyperactivation can promote this condition. Osteoclasts are multinucleated cells, and their activity directly correlates with their ploidy level. Multinucleation associates with the accumulation of extra centrosomes that can activate the PIDDosome pathway. Depending on cell type, this can lead to a p53/p21-mediated cell cycle arrest, or BCL2-regulated apoptosis. Here, we report that the PIDDosome controls polyploidization in osteoclasts and its absence triggers bone erosion in mice. PIDDosome activation in osteoclasts depends on the presence of extra centrosomes bearing the distal appendage protein ANKRD26. Consistently, loss of Ankrd26 phenocopies PIDDosome-deficiency in osteoclasts. Surprisingly, p53 and p21, which restrict cell cycle progression in the presence of extra centrosomes, are not involved in limiting osteoclast polyploidization and function. In support of this notion, bones from p53-/- mice display a higher trabecular bone mass phenotype, and osteoclasts generated from p21-/- mice show normal OC ploidy and function. Altogether, we document that the PIDDosome regulates bone homeostasis by regulating osteoclast polyploidization and their bone-resorbing function independently of the canonical p53/p21 axis, hinting towards unknown downstream effectors. We propose that modulation of PIDDosome activation might be therapeutically exploited for osteoporosis treatment, while its inhibition may ameliorate osteopetrosis symptoms.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, and mechanoadaptation. Genetic mutations, altered post-translational modifications, and environmental stress can disturb these assemblies, but the evidence does not always establish whether condensates are causal drivers of disease or downstream responses to injury. This review examines how biomolecular condensates and LLPS-related mechanisms have been implicated in osteoporosis, osteoarthritis, skeletal muscle atrophy, bone and soft tissue sarcomas, and neuromusculoskeletal diseases. We focus on the strength of the available evidence, distinguish correlative observations from causal mechanisms where possible, and discuss how condensates may connect non-coding genetic variants, mechanical cues, metabolic signals, and disease phenotypes. We also assess the translational potential and limitations of condensate-based biomarkers, therapies that target pathological condensates, and phase-separation-inspired delivery systems. A central message is that biomolecular condensates offer a useful framework for musculoskeletal biology, but clinical translation will require disease-specific targets, human-relevant models, selective delivery, and rigorous tests of causality.

Film bulk acoustic resonators (FBARs) are widely used in radio frequency (RF) filters for wireless communication because of their high operating frequency and high quality factor. With the increase of high-power applications, ensuring device robustness has become a critical challenge. This study presents an investigation into the high-power failure behaviors and mechanisms of FBARs, specifically examining the role of active area, film thickness, and geometry. Experimental results demonstrate that small-area FBARs exhibit distinct failure characteristics compared to large-area devices. Small-area devices are governed by progressive spallation at electrode edges, which is induced by high-temperature oxidation and stress concentration, whereas large-area FBARs are prone to sudden structural fracture or short-circuiting caused by excessive thermal stress. Crucially, the study reveals a thickness-dependent transition in large-area devices, where short-circuiting and structural fracture correspond to distinct stress-severity regimes. Furthermore, dynamic evaluations demonstrate that these FBARs preserve strict electrical linearity right up to the point of catastrophic collapse. Based on these phenomenological findings, a thermo-mechanical coupling mechanism is proposed that goes beyond the conventional thermal-only model. Finally, we propose new design guidelines to enhance the power handling capability of FBAR devices.

In this study, we investigate the mechanical elastic and failure behavior of porcine small intestinal walls (SIWs). In order to comprehensively examine the small intestine (SI) mechanically, all three sections of the SI, the duodenum, jejunum, and ileum, are examined. Single-edge notched tensile (SENT) experiments are performed on the entire wall structure as well as on the individual layers (serosal, muscular, and mucosal layer). In addition, the experiments are carried out in different loading directions (0°, 45°, and 90°) with respect to the tissue orientation. Overall, the elastic mechanical behavior for all regions and all layers is characterized by a typical, exponential, nonlinear behavior in combination with a partially distinct anisotropic behavior, featuring an broad elastic region λmax of 1.1 to 1.7, with corresponding stresses Pe of approximately 2 to 330 kPa. Failure behavior, as characterized by the critical energy release rate GC, exhibits obvious layer dependence. The average GC value of the mucosal layer is approximately four times higher than that of the muscular layer (1-2 N/mm), while the serosal layer has the highest values, reaching 6-10 N/mm. Additionally, the fracture behavior of the combined muscular and serosal layers of the duodenum, jejunum and ileum can be explained by classical laminate theory. However, the results of the entire wall indicate complicated interlayer behavior between the mucosal and muscular layers. Furthermore, the crack-tip tracking method and local deformation obtained from optical measurements help achieve a clearer understanding of crack initiation and propagation. These results provide a comprehensive dataset about the failure characteristics of the SI that can be used as input or for validating failure models in the future. Statement of Significance: This study is the first to report on experiments involving the failure of the porcine small intestine. The study investigates the region-, orientation-, and layer-specific mechanical properties of the small intestine in order to gain insight into its behavior under intact and failed conditions. Although layer-specific experimental studies are essential for a comprehensive understanding of small intestine function, they have received little attention to date. Additionally, this study examines crack propagation direction during uniaxial tensile tests. The study provides a unique database that improves our understanding of small intestine failure behavior and serves as a basis for corresponding models.

A strong crosstalk exists between endoplasmic reticulum (ER) stress and synovitis. Beyond their canonical role in protein folding, ER stress chaperones may promote inflammation, cell survival, and fibroblast activation under pathological conditions. This study aimed at localizing and quantifying 11 ER stress proteins (BiP, HYOU1, MANF, PDIA4, GANAB, HSP90B1, TXNDC5, DNAJB11, LMAN1, ERP29, CALR) in human inflamed synovial membranes and at investigating their expression in fibroblast-like synoviocytes (FLS) under ER stress, pro-inflammatory, or pro-fibrotic stimuli. By immunohistochemistry, on a first cohort of formalin-fixed paraffin-embedded (FFPE) biopsies obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPPA), and rheumatoid arthritis (RA), these ER chaperones were primarily localized to the lining in low-grade inflammation (Tak <4) and expanded to the sublining under high inflammatory conditions (Tak ≥4), with a widespread distribution in RA. Imaging mass cytometry, applied to a second cohort of FFPE tissue samples collected from patients diagnosed with OA and RA, revealed the co-expression of ER stress proteins with CD55⁺ FLS in the lining and their progressive infiltration into the sublining along with CD34⁺CD31- FLS during inflammation. These observations were confirmed by immunofluorescence on a larger cohort of OA patients. As inflammation progresses, there is a loss of co-expression with CD55 in the lining, accompanied by a gradual shift towards co-expression with CD34 in the sublining. In vitro, ER stress proteins, particularly BiP, HYOU1, MANF, PDIA4, HSP90B1, LMAN1, CALR, and DNAJB11 are overexpressed in human OA FLS following ER stress, pro-inflammatory or pro-fibrotic stimulation, with BiP, PDIA4, HSP90B1, ERP29, and CALR also being secreted. PDIA4 emerged as a central player: its depletion significantly impaired FLS proliferation and migration, highlighting a direct role in driving synovitis. This study provides the first spatial and functional characterization of ER chaperones in human arthritic synovium, linking ER stress to fibroblast plasticity, inflammation, and fibrosis.

Interoception is a core process through which the body perceives its internal state and regulates physiological homeostasis via bidirectional communication between the central and peripheral nervous system. Skeletal interoception is a specific circuitry for the brain control of the weight-bearing system, particularly responsible for sensing bone-derived internal signals to maintain skeletal homeostasis in response to mechanical loading. Recent studies uncovered that prostaglandin E2 (PGE2) plays a crucial role in skeletal interoception, and is therefore involved in major skeletal disorders and pain conditions such as low back pain, osteoarthritis and particularly ankle osteoarthritis (AOA). Ankle pain is clinically common, with a prevalence of 9%-15% among adults, severely impairing work productivity and quality of life. This article reviews the progress of skeletal interoception in skeletal pathogenesis and pain, with AOA as an example. Specifically, it discusses PGE2 and skeletal interoception in relation to pain and inflammation. We also attempted to interpret non-steroidal anti-inflammatory drugs (NSAIDs), surgical interventions and Traditional Chinese Medicine (TCM) therapies, especially acupuncture and electroacupuncture, in the therapy of pain and osteoarthritis from the viewpoint of skeletal interoception. Interoception is an emerging science in understanding how the brain regulates peripheral organs. Skeletal interoception mediated by PGE2 provides an opportunity to understand the potential of NSAIDs and acupuncture in regulating interoception for the treatment of skeletal disorders including ankle pain.

Meniscal injury is a leading cause of early-onset osteoarthritis, yet regenerative options remain limited. This study investigates a nonwoven polyethylene terephthalate (PET) scaffold for meniscus tissue engineering and assesses its capacity to support mesenchymal stromal cell (MSC) proliferation and chondrogenic differentiation under dynamic loading. Human MSCs are seeded onto PET scaffolds (400-420 g/m2, 85% porosity) and cultured for up to 21 days under basal medium (Ctr), chondrogenic differentiation conditions (ChD), or ChD combined with dynamic loading (ChD + Dyn, 12% strain, 1 Hz, 1 h/day, 5 days/week). PET scaffolds support uniform MSC adhesion and colonization. Compared with ChD alone, ChD+Dyn significantly increases cell proliferation and transiently upregulated chondrogenic markers (SOX9, ACAN, COL1A1, COL2A1) while suppressing the hypertrophic marker COL10A1. Although collagen deposition and construct biomechanics remained unchanged over 21 days, glycosaminoglycan accumulation was reduced in the ChD + Dyn group compared with ChD. RNA sequencing revealed distinct mechanosensitive transcriptional signatures induced by dynamic loading, particularly in genes associated with extracellular matrix remodeling, mechanotransduction, and developmental signaling pathways. These findings demonstrate that nonwoven PET provides a mechanically robust scaffold for meniscus tissue engineering and that dynamic loading promotes MSC proliferation while transiently regulating chondrogenic differentiation and mechanoadaptive matrix remodeling toward a meniscus-like phenotype.

Critical-size long bone defects remain a major clinical challenge, with treatments such as autografts or distraction osteogenesis causing donor-site morbidity, infection, or failure to restore complex bone architecture. Tissue-engineered implants that recapitulate native fracture healing provide a promising solution. However, scalability for dense cellular constructs is lacking. To address this, we bioprinted high-cell-density implants using rheologically competent sacrificial alginate bioinks. The constructs were supported by partially crosslinked alginate during bioprinting and chondrogenic differentiation, after which selective EDTA-mediated alginate dissolution generated scaffold-free implants. Quality characterization confirmed chondro-osteogenic signatures and extracellular matrix gene upregulation. Upon in vivo implantation in immunocompromised mice, implants underwent endochondral ossification, forming cortical and trabecular bone with bone marrow compartments. Integration with a suspension bioreactor enabled production of human-sized proof-of-concept implants. This work establishes a scalable 4D biofabrication process that integrates 3D bioprinting with dissolvable sacrificial alginate bioinks and results in scaffold-free, bone-forming callus implants.

Artificial prosthetic manufacturing is moving toward patient-specific design and production, and zirconia-based three-dimensional printing is emerging as a promising approach because of its mechanical properties and biocompatibility. Yet the step from laboratory development to clinical use is still limited by the gap between laboratory-scale process optimization and clinically relevant validation of performance, reproducibility, and long-term reliability. This review provides an application-oriented overview of zirconia-based photopolymerization additive manufacturing for dental, orthopedic, and scaffold applications, discussing relevant functional requirements alongside key processing parameters, postprocessing steps, and quality-critical variables. We outline major bottlenecks, such as optical scattering and slurry rheology during fabrication, as well as defects and dimensional deviations introduced during debinding and sintering, and we discuss recent performance-oriented strategies, including triply periodic minimal surface (TPMS) architectures and functionally graded additive manufacturing (FGAM) routes. Finally, we highlight the critical requirements for clinical translation, including qualification-ready process control, lot-to-lot manufacturing consistency, and robust durability validation under clinically relevant conditions. Taken together, these aspects establish a process-defect-performance relationship, where photopolymerization parameters govern defect evolution during debinding and sintering and, ultimately, determine the mechanical reliability and clinical performance of zirconia-based prostheses. Addressing these challenges will be essential for bridging the gap between laboratory-scale demonstrations and the scalable production of patient-specific zirconia prostheses.

To comprehensively evaluate the efficacy and exercise prescription parameters of traditional Chinese exercises (TCEs) on health outcomes in patients with musculoskeletal disorders (MSDs) and rigorously assess the certainty of the evidence. Umbrella review. PubMed, Embase, Cochrane Library, Scopus, Web of Science, PEDro, Ovid Medline, CINAHL and SPORTDiscus databases were searched from inception to 6 March 2026. Systematic reviews with meta-analyses of randomised controlled trials (RCTs) that investigated TCE interventions for individuals with MSDs. 92 meta-analyses, comprising data from 1744 primary RCTs, were included, yielding 547 unique outcome associations. TCE modalities included mixed/unspecified TCEs (37.3%), Tai Chi (41.5%), Baduanjin (11.0%), Yijinjing (4.2%), Qigong (3.8%), Wuqinxi (1.8%) and Daoyin (0.4%). Targeted MSDs spanned 10 categories, most commonly arthritis (38.8%). Methodological quality was high for 65 (70.7%) meta-analyses (A Measurement Tool to Assess Systematic Reviews). Applying the Grading of Recommendations, Assessment, Development and Evaluations framework, 23 associations (4.2%) were supported by high-certainty evidence and 179 (32.7%) by moderate-certainty evidence. High-certainty evidence demonstrated that TCEs significantly improved physical function in knee osteoarthritis, enhanced mental health in patients with knee osteoarthritis and neck pain and improved sleep quality in fibromyalgia. Tai Chi significantly alleviated chronic MSD-related pain and stiffness while increasing bone mineral density (BMD) in participants with osteopenia/osteoporosis. Subgroup analyses indicated that interventions with longer duration, higher frequency and moderate-to-high weekly volume were associated with greater clinical gains for knee osteoarthritis and osteoporosis. This umbrella review consolidates high-quality evidence demonstrating that TCEs, especially Tai Chi, provide multidimensional benefits for MSDs, improving function, pain, mental health, sleep and BMD with sustained practice. CRD420251080573.

Shoulder pain is a common and disabling condition most often managed in primary care. This review provides an evidence-based update on the diagnosis and management of shoulder pain to support clinical decision-making and improve patient outcomes. Shoulder pain arises from benign, self-limiting soft-tissue disorders or rare but serious causes. In primary care, most cases are nontraumatic and involve periarticular soft tissues. The subacromial region is the most frequent source of pain, and the term subacromial pain is preferred over overlapping and inconsistently defined labels such as rotator cuff tendinopathy or tear, impingement syndrome, or subacromial bursitis. Less commonly, pain originates from the glenohumeral joint, as in glenohumeral osteoarthritis or adhesive capsulitis. Assessment should focus on a detailed history and physical examination to assess pain patterns and movement limitation and to exclude serious causes, such as infection, malignant neoplasm, or nonshoulder referred pain. Once these are excluded, first-line treatment is similar for most patients and aligns with recommended care for other regional musculoskeletal concerns: education about the favorable natural history, symptom relief and activity modification if needed, and watchful waiting. Early imaging is not indicated in the absence of significant trauma or suspicious features, such as fever, unexplained weight loss, or history of malignant neoplasm, as structural abnormalities often do not correlate with symptoms, rarely alter management, and may lead to overdiagnosis and overtreatment. Specialist referral should be reserved for suspected serious pathology, such as infection, malignant neoplasm, fracture, or dislocation; significant functional or neurologic deficit; features suggestive of systemic inflammatory disease; or persistent or worsening pain and debility. High-certainty evidence indicates that subacromial pain does not benefit from surgical intervention. Shoulder pain is the third most common musculoskeletal presentation in primary care. Although causes vary, the initial management is largely the same once serious conditions have been excluded. Most patients with subacromial pain will fully recover with minimal intervention and can be safely treated with supportive care. Imaging and referral to surgical subspecialists should be reserved for rare and carefully selected cases to avoid unnecessary intervention.

Physics-Informed Neural Networks (PINNs) have recently emerged as powerful tools for solving partial differential equations (PDEs), with the Deep Energy Method (DEM) proving especially effective in fracture mechanics due to its energy-based formulation. Despite these advances, existing DEM approaches require dense collocation near cracks, face stability challenges, and typically treat discrete and continuous fracture models separately. To overcome these limitations, we introduce the Extended Deep Energy Method (XDEM), a unified deep learning framework that incorporates both displacement discontinuities and crack-tip asymptotics in the discrete setting, while flexibly coupling displacement and phase fields in the continuous setting. This integration enables accurate fracture predictions using uniformly distributed, relatively sparse collocation points. Validation across benchmark problems including stress intensity factor evaluation, straight and kinked crack growth, and complex crack initiation demonstrates that XDEM consistently outperforms standard DEM in accuracy and efficiency. By bridging discrete and phase-field models within a single framework, XDEM establishes a robust foundation for applying AI to fracture mechanics and opens new avenues for predictive modeling in engineering and materials science.

Bone metastasis (BM) frequently occurs in various types of cancer, particularly in prostate (PCa), breast (BCa), renal (RCC), and lung cancers (LCa), yet no reliable biomarker has been established. In this study, we evaluated the clinical utility of serum growth differentiation factor 15 propeptide (sGDPP), secreted by both osteoblasts and osteoclasts, as a diagnostic biomarker for BM across common solid tumors. A total of 799 participants were enrolled, including 107 healthy donors, 242 patients with PCa, 113 patients with BCa, 159 patients with RCC, and 178 patients with LCa. Among the cancer patients, 398 had no BM and 294 had BM. The diagnostic performance for BM was compared among conventional biomarkers: alkaline phosphatase (ALP), lactate dehydrogenase (LDH), estimated glomerular filtration rate, osteocalcin, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b, procollagen type I N-terminal propeptide (PⅠNP), and sGDPP. Among all patients, ALP, LDH, PⅠNP, and sGDPP levels were significantly higher in patients with BM than in those without BM. Particularly, sGDPP showed the highest area under the curve values (0.91 in PCa, 0.80 in BCa, 0.81 in RCC, and 0.51 in LCa). Multivariate analysis showed sGDPP is an independent diagnostic biomarker for BM in PCa, BCa, and RCC (p < 0.01). Additionally, sGDPP in patients with osteoporosis did not significantly differ from that in healthy donors, suggesting that sGDPP increases only when tumor cells seed and proliferate in the bones. Overall, sGDPP demonstrated superior diagnostic performance compared to conventional biomarkers and may complement imaging tests in detecting BM.

Use of non-vitamin K oral anticoagulants (NOACs) is associated with reduced dementia risk in patients with atrial fibrillation (AF), but their impact on cognitive function and clinical outcomes in AF patients with Alzheimer's disease (AD) remains unclear. Based on the Swedish Registry for Cognitive/Dementia Disorders, individuals with incident AD during May 2007-December 2020 and pre-existing AF were identified. Anticoagulant use at baseline was categorized as non-use, warfarin, or NOACs. Inverse probability of treatment weighting was employed to balance covariates. Mixed-effects models were used to assess the association between anticoagulant use and cognitive decline measured by the Mini-Mental State Examination (MMSE). Cox proportional hazards models were used to examine risks of all-cause mortality, ischaemic stroke/systemic embolism, major bleeding, and fracture. Among 7308 eligible individuals (3341 non-users, 2277 warfarin users, and 1690 NOAC users), NOAC users exhibited significantly slower cognitive decline compared to non-users (difference in MMSE scores β = 0.23 points/year, 95% confidence interval [CI] 0.11-0.36) and warfarin users (β = 0.21 points/year, 95% CI 0.10-0.33). Compared to non-use of anticoagulants, NOAC use was associated with significantly lower rates of mortality (hazard ratio [HR] 0.81; 95% CI 0.72-0.91), ischaemic stroke/systemic embolism (HR 0.66; 95% CI 0.53-0.82), and fracture (HR 0.79; 95% CI 0.64-0.97), without an increased rate of major bleeding (HR 1.05; 95% CI 0.84-1.32); in contrast, warfarin use was associated with significantly lower rates of mortality (HR 0.88; 95% CI 0.80-0.97) and ischaemic stroke/systemic embolism (HR 0.85; 95% CI 0.72-1.00), but a higher rate of major bleeding (HR 1.31; 95% CI 1.09-1.56). Compared to warfarin, NOAC use was associated with lower rates of ischaemic stroke/systemic embolism (HR 0.78; 95% CI 0.62-0.98) and major bleeding (HR 0.80; 95% CI 0.64-1.01), and non-significant reductions in mortality and fracture. In patients with AF and AD, NOAC use was associated with modestly slower cognitive decline and more favourable effectiveness and safety profiles, compared to warfarin or no anticoagulation.

Hallux rigidus, or osteoarthritis of the first metatarsophalangeal joint (MTPJ), causes pain and functional limitation. No randomized trials have compared surgery with the natural course of the disease. To compare first MTPJ arthrodesis-a widely used surgical intervention-with watchful waiting in reducing walking-related pain in symptomatic hallux rigidus at 12 months after randomization. Single-center, parallel-group, randomized, controlled, superiority trial with 12-month follow-up. (ClinicalTrials.gov: NCT04590313). Orthopedic department of a tertiary care hospital in Finland. Adults aged 40 years or older with radiographically confirmed (Coughlin-Shurnas grade I to III) hallux rigidus with symptoms over a year and a walking pain score of 4 or higher on a numerical rating scale (NRS) of 0 to 10 were eligible. Exclusion criteria included type 1 diabetes mellitus, rheumatoid arthritis, and hallux valgus angle greater than 15°. Participants were randomly assigned in a 1:1 ratio to surgery with first MTPJ arthrodesis using lag-screw and dorsal plating or to watchful waiting. The primary outcome was walking-related pain (NRS of 0 to 10) at 12 months. The prespecified minimal clinically important difference was 1.7 points. Between November 2021 and June 2024, 90 patients were randomly assigned (45 per group). The mean age was 58.1 years, and 89 participants completed the 12-month follow-up. At 12 months, the observed mean walking-related pain was 1.3 in the arthrodesis group and 5.7 in the watchful waiting group (adjusted mean difference, -5.0 points [95% CI, -6.1 to -3.9 points]), exceeding the prespecified minimal clinically important difference and favoring arthrodesis. Single-center design. Among adults aged 40 years or older with painful hallux rigidus, first MTPJ arthrodesis provides a superior and clinically significant reduction in walking-related pain at 12 months compared with watchful waiting. Suomen Lääketieteen Säätiö Foundation, Finland.