Search Results (293)

Noninvasive light-based measurements have recently been suggested for monitoring fracture healing and for the development of smart implants. The aim of this study was to collect the first exploratory longitudinal in vivo data from human distal fibular fractures. In this prospective observational pilot study, blood flow, oxygen saturation, and relative hemoglobin were noninvasively measured by using combined laser Doppler and white-light spectroscopy at depths of 3 mm and 10 mm. In patients with fibular fractures, measurements were performed at 1–3 days, 2 weeks, 6 weeks, 3 months and 6 months after surgery. Patients with fibular nonunion and healthy control participants underwent a single measurement. Fourteen longitudinal fracture patients, a nonunion patient, and 42 controls were included. In the longitudinal fracture group, oxygen saturation at a depth of 10 mm significantly decreased from baseline to 2 weeks (p < 0.001) and remained at a low plateau significantly below healthy control levels throughout the 6-month period. Blood flow and relative hemoglobin levels did not longitudinally change but remained significantly elevated compared with controls (p < 0.001). A single nonunion case demonstrated a markedly low oxygen saturation value (8.3%) combined with increased blood flow. Fibular fractures treated with plate fixation exhibit a prolonged low-oxygen saturation plateau, in contrast to the rapid recovery observed in tibial shaft fractures, possibly due to differences in anatomy or healing mechanisms. The low oxygen saturation observed in the nonunion requires further investigation, as it may have prognostic potential. Full article

Background: Forearm nonunions represent a challenging clinical condition that significantly impairs upper limb function. Various surgical techniques have been proposed, including vascularized bone grafts. Although these procedures are not considered first-line treatment, they play a crucial role in complex or recalcitrant cases, particularly after failure of conventional methods, where their superior biological potential can significantly enhance bone healing. Despite the widespread use of the medial femoral condyle corticoperiosteal flap, simultaneous bilateral harvest has not been previously described in the literature. Case Presentation: We report the case of a 50-year-old male presenting with persistent nonunions of both the radius and ulna following previous osteosynthesis and revision surgery with iliac crest bone graft. The patient was successfully treated using bilateral vascularized corticoperiosteal free flaps harvested from both medial femoral condyles. Conclusions: Double vascularized corticoperiosteal free flaps may represent an effective and reliable option for the treatment of complex forearm nonunions, especially in cases with multiple previous surgical failures. To the best of our knowledge, this case represents the first report of simultaneous bilateral medial femoral condyle corticoperiosteal flap harvest. Full article

Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication. Full article

Background: Vitamin K2 (menaquinone) has been studied as a molecule with important effects on bone metabolism and has been proposed as a potential adjuvant in fracture healing, particularly under osteoporotic conditions. However, its functional impact on osteoporotic fracture healing remains largely undefined. The aim of this study was to evaluate the effects of vitamin K2 supplementation, in the form of menaquinone-4 (MK-4) and menaquinone-7 (MK-7), on fracture healing in an ovariectomized rat model of osteoporosis. Methods: Forty Wistar rats were included in this study and allocated to four equal groups: Sham control, ovariectomized control, MK-4, and MK-7. Osteoporosis was induced by bilateral ovariectomy, and 12 weeks after ovariectomy, a femoral fracture was produced and fixed by intramedullary nailing. Starting on postoperative day 2, the MK-4 group received 5 mg/kg/day of MK-4, while the MK-7 group received MK-7 at a dose of 0.05 mg/kg/day. Fracture healing was assessed primarily by biomechanical testing using a three-point bending test and was further analyzed by histological and biochemical parameters, including CTXI, PINP, ucOC, BALP, and ALT. Results: Vitamin K2 supplementation did not improve functional fracture healing. In both treatment groups, fractures showed nonunion-like mechanical behavior, precluding meaningful quantitative biomechanical comparison. Although histological and biochemical findings, particularly in the MK-4 group, showed some degree of biological activity, these changes did not translate into mechanically competent bone union. Both treatment groups showed a tendency toward impaired healing, with progression toward nonunion-like behavior under the present experimental conditions. No significant hepatic toxicity was observed. Conclusions: In this ovariectomized rat femoral fracture model, vitamin K2 supplementation with either MK-4 or MK-7 did not enhance functional fracture healing despite evidence of biological activity of the treatment. These findings suggest a discrepancy between molecular or histological effects and biomechanical outcomes, indicating that, under the conditions tested, vitamin K2 is insufficient to overcome impaired healing in osteoporotic bone and may adversely influence fracture repair under these experimental conditions, although the mechanism remains uncertain. Full article

Atrophic fracture nonunion is a clinically challenging form of failed bone repair, particularly under inflammatory conditions, but the cell-intrinsic programs that impair the function of skeletal stem/progenitor cells (SSPCs) remain incompletely defined. Here, we integrated public and in-house single-cell RNA sequencing datasets from mouse periosteum, normal fracture healing, and inflammation-associated fracture nonunion models to characterize stromal cell fate changes. Trajectory inference, transcription factor network analysis, and intercellular communication modeling were combined with in vitro and in vivo validation experiments. SSPCs in the nonunion microenvironment were arrested in an undifferentiated state and acquired a pro-inflammatory and pro-ferroptotic phenotype, with enrichment of ferroptosis-related genes including Acsl4. Computational analyses nominated IL-1β as a candidate upstream inflammatory signal, with neutrophils representing a potential source, and linked this signal to NF-κB activation and increased Epas1 activity in SSPCs. In primary SSPCs, IL-1β induced lipid peroxidation, intracellular ferrous iron accumulation, ferroptosis-related protein expression, and impaired osteochondrogenic differentiation. Ferroptosis inhibitor treatment further attenuated IL-1β-induced ferroptosis-related protein changes, supporting pathway specificity. Pharmacological inhibition of EPAS1 with PT2385 attenuated IL-1β-induced ferroptotic stress and restored SSPC differentiation in vitro, while also improving IL-1β-impaired fracture repair in vivo. Mendelian randomization analysis provided additional genetic evidence supporting potential links among IL-1β, EPAS1, and human nonunion risk. Together, these findings suggest that an IL-1β/EPAS1-associated ferroptotic program contributes to SSPC dysfunction during inflammation-associated fracture nonunion and may represent a potential targetable mechanism for improving impaired bone repair. Full article

Background/Objectives: Rami fractures in anteroposterior compression (APC)-type pelvic ring injuries show favorable outcomes with conservative management in isolated settings; however, the necessity of direct rami fixation when posterior instability is present remains unclear. This study aimed to determine whether adding direct rami fixation to symphyseal plating improves clinical and radiologic outcomes in APC-type pelvic ring injuries. Methods: This retrospective cohort study included a final cohort of 98 patients with APC type II or III pelvic ring injuries and concomitant pubic rami fractures treated at a Level 1 trauma center (2014–2022). All patients underwent plate-based symphyseal fixation, classified into four groups by fixation strategy. Primary outcomes were rami nonunion and implant-related complications, analyzed with parsimonious multivariate logistic regression (events-per-variable ratio ≥ 10). Results: Among 98 patients (mean age 45.4 ± 16.2 years; 76.5% male), complete posterior ring injury was independently associated with rami nonunion (aOR 8.176; 95% CI 2.448–27.309; p = 0.001), implant-related complications (aOR 3.364; 95% CI 1.250–9.049; p = 0.016), and overall complications (aOR 4.292; 95% CI 1.640–11.233; p = 0.003). Female sex was an additional independent predictor of overall complications (aOR 4.226; 95% CI 1.443–12.378; p = 0.009). Direct rami fixation was not a significant predictor of any outcome but consistently increased operative time in pairwise subgroup comparisons (Group 1 vs. 2: 64.9 vs. 106.9 min, p < 0.001; Group 3 vs. 4: 95.1 vs. 153.5 min, p < 0.001). Pairwise subgroup comparisons were severely underpowered (power range 5–16%); therefore, the absence of statistically significant differences between fixation strategies should not be interpreted as evidence of equivalence. Because more complex fractures were more likely to receive additional fixation, confounding by indication further limits these comparisons. Conclusions: Complete posterior ring injury was the dominant predictor of adverse outcomes in APC-type pelvic ring injuries. In this underpowered exploratory analysis, adding direct rami fixation to symphyseal plating did not demonstrate a statistically significant reduction in complications but was associated with longer operative time. Direct rami fixation may be reserved for selected cases with marked displacement, poor indirect reduction, or compromised bone quality; larger prospective studies are needed before firm recommendations can be made. Full article

Critical size bone defects (CSBD) remain a major challenge in orthopedic surgery. Autologous bone grafting is considered the gold standard but is limited by restricted availability and significant donor-site morbidity. Synthetic bone substitutes offer an alternative; however, these materials are avital and lack osteoinductive properties. This study evaluated whether intraoperative bioactivation of bone substitutes using a surgical suction handle can safely enhance their regenerative potential. Fifty patients with CSBD, non-unions, or high-risk defects were enrolled, and calcium phosphate-based ceramics were intraoperatively coated with autologous tissue via a surgical suction handle and implanted into the defects. Clinical outcomes—including pain, range of motion, and wound healing—were scored using a standardized system, with all patients achieving results in the “excellent” range (10–13 points). Radiographic follow-up showed progressive cortical and extracortical bone formation in all patients. Surgeons reported high ease-of-use for the device, and no device-related complications occurred. Although biomaterial resorption was incomplete in some cases (36% with <75% resorption at six months), no patient required revision surgery. Our data indicate that intraoperative bioactivation of bone substitutes using a surgical suction handle is safe, feasible, and promotes local bone regeneration, providing a minimally invasive and practical approach to enhance the performance of synthetic grafts in challenging defects. Full article

One of the complications of both surgical and non-surgical treatment of fractures is the development of non-union. The 5–10% incidence of non-union quoted in the international literature is thought to be an underestimate of the real magnitude of this clinical problem. The etiology of atrophic non-union is multifactorial, involving biological, mechanical, infectious, and host-related factors. Much of the evidence regarding its pathogenesis is heterogenous and largely hypothesis generating. This heterogenicity has contributed to the wide range of treatment strategies used to address an atrophic non-union, with variable success rates. This structured narrative review summarizes current insights into the pathogenesis of atrophic non-union, including the inflammatory and immune response, the role of mesenchymal stem cells, bone morphogenetic protein, and the mechanisms of remodeling and angiogenesis. It also outlines an algorithmic approach to management, including the exclusion of occult infection, assessment of mechanical stability, optimization of modifiable host factors, and, finally, a graded approach to enhance the biological and mechanical environment of the non-union. Full article

Background: Nontuberculous mycobacteria (NTM) skin infections pose significant diagnostic challenges in clinical practice, due to nonspecific clinical/histopathological features and limitations of conventional pathogenic detection methods. Metagenomic next-generation sequencing (mNGS) offers a promising approach but requires further evaluation. Methods: A prospective pilot study at Peking Union Medical College Hospital enrolled 20 patients with cutaneous NTM infection, confirmed by positive skin culture or mNGS. All patients underwent thorough clinical assessment, skin biopsy for histopathology and culture, and mNGS testing of skin tissue. Treatment was based on identified species and disease extent. Treatment outcomes were tracked. Results: Among 20 patients (median age 45.5 years), fingers were the most common site affected (n = 10), followed by forearms (n = 7), hands (n = 4), and face (n = 4). Mycobacterium marinum was the predominant pathogen (n = 12), associated with fish bone puncture, followed by M. abscessus (n = 4). mNGS demonstrated a substantially higher positivity rate than culture (95% [19/20] vs. 30% [6/20]) and delivered results faster. Histopathology revealed granulomatous inflammation in all cases. Nineteen patients presented with non-disseminated disease; one immunocompromised patient (GATA2 deficiency) had disseminated M. abscessus infection. Treatment success was achieved in 17 patients (85%) with tailored antibiotic regimens. Adverse drug effects occurred in seven patients. Conclusions: In this pilot study of cutaneous NTM infections, mNGS enabled more rapid diagnosis relative to conventional culture. Clinical presentation and exposure history correlate with specific NTM species. Integrating mNGS with clinical assessment significantly improves diagnosis and management. Full article

Hydroxyapatite–calcium sulfate (HACaS) bone cements have been clinically established. Combining HACaS with an antiresorptive (zoledronic acid, ZA) and osteoanabolic agent (bone morphogenic protein 2; BMP-2) may enhance the performance of HACaS bone cements in challenging indications, but it must be ensured that this does not impair their setting and mechanical properties. This study established a Vicat/Gillmore-inspired indentation protocol to quantify force-based endpoints and the setting of HACaS with biological adjuvants. HACaS was mixed with or without ZA and/or BMP-2 at 0 min and after a 2 min pre-setting phase with reduced NaCl content (lower liquid-to-powder ratio). For each time point (3–90 min), three cylindrical pellets (Ø 4 mm, height 6 mm) underwent single indentation. Setting was defined as the maximum force at needle penetration, and endpoint hardness was defined as peak force at failure. For 24 h endpoints, specimens were incubated in blood at 37 °C. One-way ANOVA with Tukey’s H post hoc test was performed per time point (n = 3; 24 h endpoints n = 5). All 2 min protocols showed accelerated setting, consistent with the initial lower liquid-to-powder ratio. ZA significantly delayed setting and remained lowest at 90 min and after 24 h in blood. Mixing sequence and vehicle composition critically influenced early mechanical properties and should be considered in the further preclinical evaluation of HACaS with osteoanabolic or antiresorptive agents. Full article

Background: Long-bone non-unions complicated by osteomyelitis remain a major reconstructive and healthcare challenge, particularly in resource-limited settings with a high prevalence of multidrug-resistant (MDR) pathogens. Conventional staged management is associated with a prolonged treatment burden, repeated procedures, and delayed functional recovery. This study evaluated the clinical, radiological, functional, and short-term safety outcomes of a single-stage approach using custom-threaded antibiotic-coated locking nails (TACLNs) in a high-resistance cohort. Methods: This prospective single-center cohort study enrolled 30 adults with osteomyelitis-associated femoral or tibial nonunion at a tertiary hospital in Peshawar, Pakistan. All patients underwent radical debridement and single-stage stabilization with a chest tube mold TACLN loaded with vancomycin and gentamicin, with culture-directed adjunctive antibiotics for resistant organisms. Outcomes were assessed at baseline, Weeks 3 and 6, and Month 6 using inflammatory markers, RUST score, VAS pain, EQ-5D-5L, ASAMI criteria, and return to work or usual activity. No formal sample size calculation was performed, and this study was exploratory in nature. Results: The cohort (mean age 44.9 ± 9.9 years) had a challenging microbiological profile, with 40.0% MDR and 13.3% extensively drug-resistant (XDR) infections. By Month 6, short-term infection control was achieved in 96.7% of patients, with significant reductions in ESR and CRP (both p < 0.001). Radiographic union was achieved in 90.0% of cases at a mean of 18.6 weeks, and the mean RUST score improved from 4.87 to 10.43 at the final follow-up. The VAS pain decreased from 5.23 at week 3 to 0.73 at month 6, EQ-5D-5L improved from 0.39 to 0.84, and 90.0% returned to work or usual activity by month 6. No cement debonding, implant failure, or nephrotoxicity was noted. Conclusions: In this single-arm exploratory cohort, TACLNs were associated with favorable short-term infection control, radiographic union, and functional recovery in osteomyelitis-associated long-bone nonunion, including in an MDR/XDR setting. The independent contribution of the threaded core design cannot be established. Larger multicenter comparative studies with longer follow-ups are needed to confirm the durability and implementation feasibility. Full article

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

Background/Objectives: Nonunion after tibiotalocalcaneal (TTC) arthrodesis remains challenging, especially in revision settings where union rates are substantially lower than in primary procedures. Biological adjuncts are commonly used to enhance healing, yet most described methods employ fibular onlay struts and cancellous autograft. To our knowledge, intramedullary placement of a fibular autograft for ankle fusion has not previously been reported. This study presents a revision of TTC arthrodesis nonunion treated with this technique and summarizes existing evidence on revision ankle arthrodesis, fibular grafting, and bone marrow aspirate concentrate (BMAC). Methods: We report a revision TTC arthrodesis nonunion managed with a decorticated intramedullary fibular autograft spanning the tibiotalar canal, supplemented with cancellous iliac crest autograft and BMAC. A review of PubMed, Scopus, and Google Scholar (search date: 1 September 2025) was performed to identify studies addressing revision ankle fusion, fibular grafting techniques, and BMAC use in foot and ankle arthrodesis. Primary outcomes included union and complications, with CT-based assessment prioritized when available. Results: At 3 months, radiographs and CT demonstrated progressive osseous bridging consistent with fusion; the patient achieved pain-free weight-bearing without complications. Conclusions: Intramedullary fibular autograft in revision TTC arthrodesis is a novel biological-mechanical strategy that leverages endosteal contact and axial stability while augmenting osteogenesis with cancellous autograft and BMAC. The review supports the biological plausibility and safety of this approach and underscores the importance of CT-based assessment. Full article

Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may require multiple surgical interventions with associated morbidity. Increasing evidence has highlighted that nonunion is a multifaceted problem, not only a result of mechanical failure, but also a product of persistent dysregulation of the osteoimmune microenvironment manifested as impaired osteogenesis and bone healing. While current approaches focus on enhanced fixation and various bone grafting strategies, these treatments often fail to coordinate healing with osteoimmune regulation. This review summarizes the emerging biologic and bioengineering approaches that target osteoimmunology to enhance fracture repair. Scaffold systems, including metals, bioceramics, hydrogels, and micro/nanoparticle formulations, are being increasingly engineered to provide structural support while directing macrophage polarization and stimulating osteogenic signaling. We also review cell-based therapies and gene-modified constructs that are being developed to introduce osteoimmunology cues that halt chronic inflammation and promote an osteogenic microenvironment. Full article

Bone remodeling is a dynamic process involving bone resorption and formation that is regulated on a cellular level and impacted by mechanical stress. A variety of Orthopedic surgery treatment strategies can affect bone remodeling, which can in turn may have long-term impacts on skeletal stress tolerance and function. This review provides a comprehensive overview of bone remodeling involved in Orthopedic surgery. Materials related to bone remodeling principles across Orthopedic surgery domains were selected and compiled using databases including PubMed, MEDLINE, AccessMedicine, and CINAHL; case studies were not included. Relevant literature was summarized for a general review of bone remodeling and as it relates to treatment principles in trauma, arthroplasty, and amputation with the aim of providing a relevant, comprehensive review. Overall, the purpose of this review is to provide an overview of bone remodeling principles that are implicated in various techniques within Orthopedic surgery. Full article