骨科领域文献阅读汇编

Mesenchymal stem/stromal cells (MSCs) are osteoregenerative; however, their therapeutic efficacy for skeletal conditions is hampered by poor bone-homing ("osteotropism"). In preclinical models, this deficit is correctable by MSC glycocalyx editing to enforce sialylated Lewis X (sLeX) expression, thereby programming osteotropism. We conducted a first-in-human clinical trial (ClinicalTrials.gov: NCT02566655) involving a single intravenous infusion of glycocalyx-edited autologous bone marrow-derived MSCs in ten women with advanced-stage osteoporosis. The protocol-mandated evaluation spanned 2 years and included clinical assessments, radiographic studies, and measurements of bone turnover markers (BTMs), bone tissue area (BTA), and bone mineral density (BMD). Thereafter, fracture and safety monitoring continued for >3 additional years for each patient. No serious adverse events occurred. Fragility fractures were markedly and durably reduced, amidst increased osteoanabolic BTM levels, BTA, and volumetric BMD. These findings indicate that glycocalyx editing effectuates MSC-based osteoporosis therapy and also refute notions that MSCs derived from older persons and/or diseased-tissue sites are biologically compromised.

Evidence regarding the effects of air pollution on bone damage remains limited and inconclusive. We aimed to investigate the individual and combined associations of long-term exposure to ambient air pollutants with fracture risk and bone mineral density (BMD). This study included 490,172 participants from the China Kadoorie Biobank who were free of prior fractures at baseline, among whom 32,545 received calcaneus BMD measurement using quantitative ultrasound in the second or third resurveys. Annual mean concentrations of particulate matter with diameters≤ 2.5μm (PM2.5), ≤ 10μm (PM10), nitrogen dioxide (NO2), and warm-season ozone (O3) were assigned to participants based on the geographic locations of recruitment clinics in their communities, using 1 × 1 km resolution. Incident fracture cases were defined as the first occurrence of fracture at any anatomical site, excluding those least likely due to osteoporosis and most likely due to severe trauma or cancer. Time-varying Cox proportional hazard models and linear mixed models were used to examine individual associations between air pollutant exposure and incident fracture risk, and longitudinal changes in BMD, respectively. Principal component analysis and quantile-based g-computation were applied to evaluate the combined effects of air pollutants and the relative contributions of each pollutant. Mediation analyses were performed to investigate the potential mediating role of BMD in the associations between pollutant and fracture risk. During a median follow-up of 12.0 years, 15,614 fractures were identified. Long-term exposure to PM2.5 and warm-season O3 was associated with an increased risk of any fracture, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.09 (1.05, 1.13) and 1.08 (1.04, 1.12), respectively, per 10 µg/m3 increase in concentration. For each unit increase in the principal component score for air pollutants, the HR (95%CI) for any fracture was 1.08 (1.03, 1.13). PM2.5 contributed most to the elevated fracture risk (70%), followed by warm-season O3 (30%). Higher levels of air pollution were associated with lower BMD, with BUA, SOS, SI, and T-score lowering by 0.263 (95%CI: 0.220, 0.305), 0.265 (0.225, 0.306), 0.299 (0.264, 0.334), and 0.311 (0.274, 0.347) (in units of standard deviation) for per principal component score increment, respectively. The decline in the latter three BMD measures accounted for 5.80-8.59% of the association between pollutants and fracture risk. Long-term co-exposure to PM2.5, PM10, NO2, and warm-season O3 was associated with lower BMD and increased fracture risk, with reduced BMD potentially acting as a modest partial mediator. PM2.5 consistently exhibited the greatest contribution to the associations between air pollutants and both fracture risk and BMD. Our findings suggest that adherence to fine particulate matter control and enhanced pollutant synergism may play an important role in bone health promotion in aging populations.

Menopause is characterized by hormonal decline, increasing susceptibility to osteoporosis, cardiovascular disease, cognitive impairment, and metabolic dysfunction. Phytoestrogens, plant-derived bioactive compounds with estrogenic and anti-inflammatory properties, have emerged as potential alternatives to hormone therapy for mitigating these risks. This review critically examines their molecular mechanisms, bioavailability challenges, and clinical applications. Their impact on bone mineral density, cardiovascular function, neuroprotection, and metabolic regulation is evaluated, alongside safety considerations. However, inconsistencies in clinical outcomes underscore the need for standardized dosing strategies and precision-based approaches informed by genetic and microbiome profiling. Beyond clinical utility, their role in sustainable nutrition and global health equity is also considered. By integrating molecular insights with translational applications, phytoestrogens represent a promising, non-hormonal strategy for improving menopausal health.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid® platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Musculoskeletal disorders (MSDs), including osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA), represent a stubborn burden in modern medicine. They share a breakdown in mitochondrial homeostasis. Mitochondrial dysfunction serves as a central pathogenic mechanism unifying these conditions and driving a paradigm shift from symptomatic management to mechanism-based therapeutic strategies. In this review, we examine how mitochondrial defects affect key cell types in bone, cartilage, and muscle, including osteoblasts, osteocytes, osteoclasts, chondrocytes, and skeletal muscle cells, with a focus on osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA) as the three primary musculoskeletal conditions that share mitochondrial dysfunction as a unifying mechanism. Impaired energy production, altered dynamics, defective quality control, and redox imbalance each contribute to disease progression. These disturbances drive oxidative damage, metabolic reprogramming, impaired mitophagy, and the release of pro-inflammatory signals known as mtDAMPs. Importantly, such defects are not irreversible, we further synthesize the emerging landscape of mitochondria-targeted strategies. These include antioxidants like MitoQ and SkQ1, metabolic modulators such as metformin and NAD⁺ boosters, mitophagy inducers like urolithin A, fission inhibitors including Mdivi-1, senolytic agents, and even mitochondrial transplantation. We conclude by proposing a precision medicine framework that matches specific mitochondrial abnormalities with mechanism-based interventions. Drawing on recent preclinical and clinical evidence, this review positions mitochondrial crosstalk as a promising foundation for developing disease-modifying therapies in musculoskeletal medicine.

One in four surgical patients carries a drug allergy label, of which an estimated 90% are incorrect. Avoidance of first-choice drug therapies can lead to worse postoperative outcomes. We sought to determine the nature and extent of any association between drug allergy labels and postoperative complications. A multicentre observational study was performed in 21 UK National Health Service hospitals. Eligible patients were ≥18 yr of age and undergoing common surgical procedures: primary hip or knee replacement, internal fixation of closed long bone fracture, colorectal resection, transurethral resection of prostate or bladder tumour, Caesarean delivery, or hysterectomy. Exclusion criteria were the use of antibiotics in the two weeks before surgery or previous participation in the study. The primary outcome was postoperative complications within 30 days after surgery, a composite outcome comprising all postoperative infections, anastomotic leak, acute respiratory distress syndrome, myocardial infarction, postoperative bleeding, pulmonary embolism, stroke, antimicrobial side-effects, and death. Among 13 646 patients, 3924 (29%) carried ≥1 drug allergy label. Labelled patients were more likely to develop postoperative complications (989/3924 [25%] vs 1926/9722 [20%]; odds ratio [OR] 1.21 [1.10-1.34]; P<0.001). They were more likely to develop surgical site infections (337/3924 [9%] vs 760/9722 [8%]; OR 1.19 [1.03-1.38]; P<0.018), and any postoperative infection (750/3924 [19%] vs 1472/9722 [15%]; OR 1.24 [1.11-1.38]; P<0.001). Labelled patients experienced an increased risk of allergic drug reactions (31/3924 [0.01%] vs 29/9722 [<0.01%]; OR 3.00 [1.77-5.09]; P<0.001), but no increase in mortality. Drug allergy labels are common, but often incorrect. Patients with drug allergy labels experience worse postoperative outcomes, including infective and noninfective complications and an increased risk of allergic drug reactions. ISRCTN Registry (ISRCTN15775657).

Stereoselective control in cyclic polyester synthesis, particularly stereosequence-defined cyclic copolyesters, has not yet been achieved in a single catalytic platform. Achieving this combination is challenging because stereocontrol requires precise chain-end discrimination, whereas ring-expansion growth that generates cyclic topology can be readily perturbed in monomer mixtures. Herein, we report lanthanum catalysts for isoselective ring-expansion polymerization of amino acid-derived O-carboxyanhydrides, affording high-molecular-weight (>100 kDa) cyclic stereoblock poly(α-hydroxy acids) with diverse pendant functional groups, narrow molecular-weight distributions (Ɖ < 1.1), and high isotacticities (Pm > 0.9, where Pm is the probability of meso linkage). Copolymerization of comonomers with opposite chiralities further enables one-pot scalable synthesis of high-molecular-weight (>90 kDa) cyclic gradient copolyesters (Ɖ ~ 1.1). The cyclic gradient copolymers exhibit simultaneously enhanced fracture strength and toughness relative to cyclic and linear block analogs, while maintaining oxygen barrier performance comparable to poly(lactic acid). These findings establish simultaneous stereosequence and topology control as a powerful strategy for accessing superior material properties, moving beyond conventional approaches that rely on changing monomer identity.

Prostate cancer (PCa) patients are at increased fracture risk due to the need for androgen deprivation therapy (ADT) and progressive bone metastases. Previous meta-analyses of randomised controlled trials suggest that androgen receptor pathway inhibitors (ARPIs) increase fracture risk. We assessed the impact of abiraterone-based treatment intensification on fracture-related hospitalisation (FRH) within the STAMPEDE trial platform. We performed a secondary analysis of two STAMPEDE trials in patients with high-risk non-metastatic (M0) or metastatic (M1) disease. Patients were allocated to either standard of care (SOC) or SOC plus abiraterone with prednisolone (AAP) or, in a later comparison, SOC+AAP with enzalutamide (Enza). A prespecified coding framework within Hospital Episode Statistics (HES) identified FRHs. Flexible parametric competing-risk models estimated 5-year cumulative incidence of FRH and sub-distribution hazard ratios (SDHR), with death as a competing risk. Between Nov 2011 and Mar 2016, 3893 patients were randomised to the STAMPEDE AAP±Enza trials. Linked HES data were available for 3102 patients in England. In M1 disease, 5-year FRH incidence was significantly lower with SOC + AAP than SOC alone (22% vs 30%; SDHR 0.77, 95%CI 0.59-0.99; p = 0.04) and with SOC + AAP + Enza than SOC alone (28% vs 38%; SDHR 0.69, 95%CI 0.54-0.88; p = 0.002). No significant difference was observed in M0 patients. Limitations include potential under-estimation of total fracture burden by exclusion of non-hospitalised fractures, lack of baseline assessment of fracture risk including bone mineral density, and longitudinal use of bone-protective therapy. Abiraterone-based treatment intensification did not increase FRH compared to SOC alone. In M1 disease, abiraterone reduced rather than augmented fracture risk, most plausibly reflecting improved metastatic bone disease control.

Wood densification offers a route to high-performance structural materials, yet permanent fixation of highly compressed wood remains challenging because hygrothermal stimuli can activate stress relaxation and dimensional recovery of the cell wall. Here, we report a heat-triggered cell-wall furfurylation strategy for stabilizing highly densified wood. A ternary acidic catalyst package composed of NH4Cl, citric acid, and itaconic anhydride remains relatively mild at room temperature but exhibits progressively enhanced acidity during heating, thereby coordinating furfuryl alcohol penetration and early stage cell-wall plasticization with subsequent curing during hot pressing. Process-resolved compression measurements support a staged transition from plasticization-dominated deformation to progressive polymer-assisted fixation. The resulting densified wood exhibits set recovery below 0.5% after immersion in water at 95 °C, together with markedly improved resistance to fungal decay and termite attack. The pronounced softening effect enables a thickness reduction of 69% without visible macroscopic fracture, while the impact toughness remains 34.9% higher than that of untreated wood. The parallel-to-grain compressive strength and modulus of elasticity increased to 3.95 and 5.62 times those of untreated wood, respectively. Chemical imaging at the cell-wall scale and scattering analyses support the association of furfuryl-derived polymer with cell-wall regions, particularly lignin-rich domains, together with enhanced cellulose microfibril packing and orientation. This work establishes progressive heat-triggered regulation of cell-wall-confined furfurylation as a strategy for expanding the processing-property window of nondelignified densified wood, reconciling high-ratio deformation, near-complete hygrothermal fixation, and toughness retention.

With the growth of the older adult population and the increasing incidence of traumatic injuries, the use of orthopedic devices has risen significantly. However, in addition to material-related limitations, one of the most serious challenges associated with these devices is the risk of infection. To address this issue, an innovative hydrogel is presented to prevent infection at the source during orthopedic surgery. This hydrogel combines polyhexamethylene biguanide (PHMB), a positively charged agent with proven broad-spectrum antimicrobial activity, with a thermosensitive polymer. The resulting formulation provides suitable viscosity for application or dip-coating onto orthopedic devices, thereby forming a stable physical and chemical barrier. The new hydrogel exhibits temperature-responsive viscosity, which enhances both adherence and controlled release at body temperature. Additionally, the hydrogel demonstrates antibacterial effectiveness against both Gram-positive and Gram-negative bacteria, along with low cytotoxicity, minimal immune response, and excellent anti-biofouling properties. These features make the developed hydrogel well suited for orthopedic surgical procedures and support its potential as a complementary approach to reducing the risk of postoperative infections.