Aims: Fracture nonunion represents a major complication in orthopaedic surgery, occurring in 5% to 10% of fracture patients. Fracture nonunions are associated with pain and loss of function, and lead to a substantial socioeconomic burden. The present retrospective cohort study analyzed direct and indirect costs and length of hospital stay, number of surgical procedures, and hospital (re-)admissions of nonunion patients.Methods: Data from 18- to 65-year-old patients surgically treated for lower limb fractures and nonunions in a German level I trauma centre between 2012 and 2018 were analyzed. A total of 193 patients with nonunion were included, and 2,511 patients with fractures served as the control group. Direct costs were calculated using reimbursement according to the diagnosis-related group (DRG). Indirect costs were calculated including daily sickness allowance and productivity loss.Results: The median healing time of nonunion patients was 45 weeks. Treatment expenses showed a 2.6-fold increase in direct costs, a 3.3-fold increase in indirect costs, and a 3.3-fold increase in total costs for nonunion patients compared to the control group. As every patient with a nonunion suffered from a fracture prior to nonunion treatment, costs were calculated by adding the median direct costs of €10,487 (IQR 9,173 to 15,262), median daily sickness allowance of €23,046 (IQR 14,892 to 36,264), median productivity loss of €85,714 (IQR 60,949 to 126,650), and median total socioeconomic burden of €123,334 (IQR 88,630 to 176,329).Conclusion: Nonunions not only pose a significant burden on the injured individual and on healthcare systems, but also have a substantial socioeconomic impact. High direct and indirect costs illustrate that healing complications need to be detected and addressed as early as possible.Cite this article: Bone Joint Res 2025;14(4):1–10.

There is evidence that bone health is closely linked to a functioning circadian rhythm. Most of the evidence comes from mice, which may exhibit some species-specific differences from humans due to their nocturnal lifestyle. To address the current lack of human model systems, the present study aimed to develop an in vitro model system that can represent diurnal changes in bone metabolism. The model is based on co-cultured SCP-1 and THP-1 cells that serve as osteoblast and osteoclast precursors, respectively. Diurnal effects were induced by replacing the FCS in the differentiation medium with human serum pools (HSPs) obtained in the morning, noon, or evening. The model system was tested for cell viability, gene expression, and osteoblast and osteoclast function. The replacement of the FCS with the HSPs increased viability and induced expression changes in circadian clock genes in the model system. Resulting alterations in osteoblast and osteoclast function led to a gradual increase in mineral density and stiffness when 3D co-cultures were differentiated in the presence of the HSPs collected in the morning, noon, or evening, respectively. Here, we present for the first time an in vitro model that can present diurnal changes in bone metabolism in the form of a snapshot. With the simple use of HSPs, this model can be used as a platform technique to investigate bone function in various situations, taking into account the time of day.

Impaired bone regeneration and wound healing represent a major clinical and socioeconomic challenge for our aging and multimorbid population. Fracture and wound healing share many common features, with transforming growth factor beta (TGF-β) being a key regulator of inflammation, angiogenesis, fibroblast activation, and matrix remodeling. The dysregulation of TGF-β signaling is a hallmark of chronic wounds, excessive scar formation, and fracture non-union. Extracellular matrix protein 1 (ECM1) plays a crucial role in the activation of latent TGF-β. As a protein of the extracellular matrix, ECM1 offers ideal conditions for the biofunctionalization of bone implants or wound patches. Its mode of action has been studied mainly in fibrosis models of the liver or heart, where TGF-β acts as a driver of the disease. The controlled knock-out or overexpression of ECM1 either promoted or improved fibrosis development. In this review, we discuss how these findings can be applied to the biofunctionalization of implants to support bone and wound healing, considering the impact of TGF-β on the different healing phases.

Extracellular matrix protein1 (ECM1) plays a crucial role in the activation of latent transforming growth factorbeta (TGFβ). Active TGFβ governs key phases of tissue repair including inflammation, fibroblast activation, angiogenesis, and matrix remodeling. Dysregulation of TGFβ signaling is a hallmark of chronic wounds, excessive scar formation, and fracture non-union. As a protein of the extracellular matrix, ECM1 offers ideal conditions for the biofunctionalization of implants. Its mode of action has been studied mainly in fibrosis models, where TGFβ acts as driver of the disease. Controlled knock-out or over-expression of ECM1 either promoted or improved fibrosis development. In this review, we discuss how the findings can be applied to the biofunctionalization of implants to support the healing of skin and bone.

Undiagnosed diabetes and prediabetes are common among trauma patients and increase perioperative complication rates, yet routine glycemic screening at hospital admission is rarely performed. We compared 10 supervised machine learning (ML) algorithms for early detection of impaired glucose metabolism in 1789 trauma surgery patients (1095 normal; 694 prediabetes/diabetes) using questionnaire data and preoperative laboratory values within a nested cross-validation framework with hyperparameter optimization. On the combined feature set, XGBoost achieved the highest area under the receiver operating characteristic curve (ROC-AUC; 0.815), followed by multilayer perceptron (0.814) and Gradient Boosting (0.813); adding blood parameters significantly improved performance for nine of ten algorithms (DeLong’s test, p < 0.05). SHapley Additive exPlanations (SHAP) and XGBoost feature gains identified six overlapping predictors, yielding a simplified model with comparable mean discrimination. Inter-model differences were small, and a fully interpretable logistic regression model remained within one percentage point of XGBoost. The best-performing model demonstrated strong calibration and a higher net benefit than either universal testing or no testing across the evaluated threshold probabilities. In routine trauma practice, such a model could identify patients who would benefit from confirmatory glycated hemoglobin (HbA1c) testing, enabling earlier detection of dysglycemia, risk-stratified glucose management, and timely referral for lifestyle intervention in patients with prediabetes.

BACKGROUND Anterior cruciate ligament (ACL) injury substantially increases the risk of premature post-traumatic knee osteoarthritis (PT-OA), resulting in long-term pain, functional limitations, and reduced quality of life. Despite rehabilitation after ACL reconstruction (ACLR), patients are often insufficiently informed about long-term osteoarthritis risk, and structured secondary prevention strategies remain uncommon. Lifestyle interventions targeting modifiable risk fac-tors, including muscle weakness, physical inactivity, and overweight, may reduce PT-OA risk. However, evidence regarding the feasibility and effectiveness of such interventions remains limited. OBJECTIVE The Knee Osteoarthritis Avoidance using a Lifestyle Approach (KOALA) was there-fore developed as a theory-informed lifestyle intervention based on previous research in the field. This pilot study evaluates its feasibility and preliminary efficacy to inform future con-firmatory trials. METHODS This monocentric single-arm pilot study evaluates a 24-week telemedicine-delivered lifestyle intervention in adults aged 18–40 years undergoing ACLR after acute traumatic ACL rupture. Participants are provisionally enrolled perioperatively and formally included 6 months postop-eratively after confirmation of eligibility. The intervention consists of two 12-week phases (KOALAintense and KOALAboost) and includes knee health education and knee assessment, nutrition education, individualized counselling, and optional supervised group exercise ses-sions. Counselling is informed by motivational interviewing principles and incorporates behav-iour change techniques, including goal setting, action planning, confidence assessment, and barrier management. The primary outcome is intervention attendance. Secondary outcomes include trial-related feasibility (recruitment, retention, and data collection procedures), inter-vention-related feasibility (attendance, treatment fidelity, acceptability, and safety), and ex-ploratory health-related outcomes. Assessments are conducted perioperatively (t0), 6 months after ACLR (t1), and 12 (t2) and 24 weeks (t3) after intervention initiation. RESULTS Funding commenced in May 2025 and was extended in April 2026. As of 29 June 2026, 51 participants had been enrolled perioperatively (t0), exceeding the target sample size (n = 46). Final inclusion at 6 months postoperatively (t6) had been completed for 31 participants, of whom 30 entered the KOALA intervention. A further 12 participants are awaiting final eligi-bility assessment at t6. The current attrition rate between preliminary inclusion (t0) and final inclusion (t6) is 15.7%, and one participant withdrew after final inclusion. The last participant is expected to complete final inclusion (t6) in August 2026, with completion of the interven-tion and final follow-up anticipated by February 2027. Study results are expected in summer 2027. CONCLUSIONS This feasibility study will determine whether the KOALA intervention achieves sufficient participant engagement to justify further evaluation. Findings will provide insights into inter-vention and trial feasibility and generate preliminary evidence regarding potential efficacy in a German clinical setting. An additional qualitative study is planned to further identify barriers and facilitators to participation and inform the optimization of intervention content, delivery, tailoring, and outcome assessment. If feasibility is demonstrated, the findings of this pilot study, will inform the optimisation of the intervention and study design, as well as the sample size estimation, of a future randomised controlled trial evaluating the efficacy of KOALA. CLINICALTRIAL