Search Results (114)

Background: Unstable pelvic ring injuries often require surgical stabilization to restore pelvic ring integrity. The anterior subcutaneous internal fixator, or pelvic INFIX, has emerged as an alternative to external fixation and open anterior fixation. This study evaluated the functional, radiographic, and complication-related outcomes of INFIX fixation for unstable anterior pelvic ring injuries. Methods: We retrospectively reviewed 21 adult patients treated with anterior pelvic INFIX for unstable anterior pelvic ring fractures, with or without posterior fixation, at a Level 1 Trauma Center between 2017 and 2024. Fractures were classified according to the AO/OTA system. Functional outcomes were assessed using the Iowa Pelvic Score and Short Form-12 questionnaire. Radiographic outcomes were evaluated according to Tornetta and Matta criteria. Complications were recorded throughout follow-up. The INFIX device was routinely removed 6 months postoperatively. Results: The cohort included 15 males and six females, with a mean age of 42.5 ± 11.1 years. Mean Injury Severity Score was 25.3 ± 9.6, and mean follow-up after implant removal was 31 (IQR 28–34) months. The mean Iowa Pelvic Score was 80.2 ± 7.4, indicating an overall good functional outcome. Mean SF-12 physical and mental scores were 49.2 ± 3.5 and 48.3 ± 7.9, respectively. Radiographic outcomes were excellent in eight patients, good in 11, and fair in two. Complications included postoperative hemorrhage, implant loosening, heterotopic ossification, and three cases of lateral femoral cutaneous nerve (LFCN) injury. Conclusions: INFIX fixation appears to be a reliable minimally invasive option for unstable anterior pelvic ring injuries, providing satisfactory mid-term functional and radiographic outcomes with an acceptable complication profile. Full article

Background/Objectives: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder causing progressive heterotopic ossification. The dental phenotype has never been systematically characterised. We quantified dental pathologies and oral health-related quality of life across three age groups of genetically confirmed FOP patients and compared them with 156 matched healthy controls (2022–2025). Methods: A total of 52 FOP patients (Group I: 1–5 y, n = 14; Group II: 6–17 y, n = 21; Group III: 18–35 y, n = 17) underwent standardised dental examination (Decayed, Missing, and Filled Teeth index (DMFT), Oral Hygiene Index Simplified (OHI-S), Angle classification, temporomandibular joint (TMJ) assessment), computed tomography (CT) densitometry, sialometry, salivary crystal analysis, and Oral Health Impact Profile-14 (OHIP-14). Statistical analysis used Kruskal–Wallis, Mann–Whitney U, Benjamini–Hochberg false discovery rate (FDR) correction, and effect sizes. Results: Caries (DMFT ≥ 4) was highly prevalent across all FOP groups (82–86%) and significantly higher than in controls (84.6% vs. 38.5%, p < 0.001). Chronic stomatitis showed large age-group differences: 7.1% in Group I vs. 100% in Group III (p < 0.001); it was universal in FOP adults vs. 6.4% in controls. Enamel hypoplasia (21.4% → 58.8%) and Angle class II malocclusion (0% → 47.1%) also showed large age-group differences. Total TMJ disorders were observed in 7.1% of Group I and 100% of Group III (p < 0.001); maximal mouth opening was lower by 17.4 mm in Group III (Cohen’s d = 2.1). Salivary flow rate was 20% lower in adults (0.35 → 0.28 mL/min, p = 0.01). Calcium phosphate crystals were detected in 3/17 adults (17.6%) and showed a preliminary correlation with CT calcification grade (ρ = 0.67, p = 0.003); given the small number of crystal-positive patients, this finding should be considered hypothesis-generating. OHIP-14 total score was higher (worse) in Group III (48.9 vs. 12.4 in Group I, Cohen’s d = 1.95). Conclusions: This cross-sectional study provides a systematic characterisation of the dental phenotype in FOP across three age groups. It shows that chronic stomatitis and TMJ dysfunction become nearly universal by early adulthood, severely impairing quality of life. The correlation between salivary calcium phosphate crystals and CT calcification generates the hypothesis of a non-invasive biomarker, requiring prospective validation. The proposed clinical phenotype and minimally invasive recommendations provide a framework for safer dental management of FOP patients. Full article

Trauma-induced heterotopic ossification (tHO) is characterized by aberrant ectopic bone formation in soft tissue following high-energy trauma, affecting >60% of combat-related amputees and >50% of major burn patients. Current prophylactic strategies (including NSAIDs, bisphosphonates, and low-dose radiation) lack mechanistic specificity, carry significant side effects, and surgical excision carries a 27% recurrence rate. This review reframes tHO pathogenesis through the neural–immune axis, arguing that ectopic bone formation is a downstream consequence of dysregulated neuroimmune signaling rather than a primary osteogenic event. Following trauma, nociceptor activation drives nociception-induced neural inflammation (NINI), releasing substance P (SP) and calcitonin gene-related peptide (CGRP), which disrupts the blood–nerve barrier, mobilizes neural crest-derived progenitor cells, and, alongside BMP-2/SMAD1/5/8 signaling and M1-polarized macrophage activation, establishes a permissive osteogenic microenvironment. A BMP-2/CGRP positive feedback loop sustains aberrant osteogenesis, converging on osteogenic transcription factors Runx2, SOX5/6/9, and Osterix. Dysregulated noncoding RNAs represent promising pre-radiographic biomarkers. This neural–immune framework motivates mechanism-based therapeutic strategies targeting CGRP (fremanezumab, erenumab), SP/NK1 signaling (aprepitant), and macrophage polarization (metformin, palovarotene, rapamycin), with multi-node combination approaches tailored to the temporal stages of tHO offering the most promise for precision prophylaxis. Full article

Heterotopic ossification (HO), the pathological formation of mature bone in non-skeletal soft tissues (e.g., muscles, tendons), severely impairs patient mobility and quality of life. Despite decades of research, systematic analysis of signaling networks across HO subtypes (acquired traumatic HO, hereditary Fibrodysplasia Ossificans Progressiva (FOP), Progressive Osseous Heteroplasia (POH)) remains insufficient, and clinical therapies suffer from high recurrence and severe side effects. This review synthesizes recent advances in HO pathogenesis: FOP involves gain-of-function activin A receptor type I (ACVR1) mutations (mostly R206H), disrupting bone morphogenetic protein (BMP)/Activin A signaling; POH arises from paternal guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) loss-of-function mutations, derepressing Hedgehog signaling via reduced cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) activity; tHO features trauma-induced inflammation/hypoxia activating BMP/transforming growth factor–beta (TGF-β) pathways. Key signaling crosstalk (e.g., BMP-Yes-associated protein (YAP)-Indian hedgehog (IHH)) is integrated, and novel therapies (ACVR1 inhibitors, Activin A antibodies, retinoic acid receptor gamma (RARγ) agonists, adeno-associated virus (AAV)-mediated ACVR1 silencing) are highlighted, with emphasis on subtype-specific efficacy. A stratified, mechanism-based HO management framework is proposed, aiming to accelerate precision therapy development and advance understanding of aberrant tissue regeneration. Full article

Myositis ossificans (MO) is a benign, self-limiting heterotopic ossification process that typically develops within soft tissues following trauma, although non-traumatic forms have also been described. Despite its benign nature, MO frequently represents a diagnostic challenge, particularly in its early stages when imaging findings may mimic aggressive soft-tissue tumors, leading to unnecessary biopsies or surgical interventions. This narrative review provides an updated overview of the classification, pathophysiology, and imaging features of myositis ossificans, with a specific focus on the time-dependent evolution of radiologic appearances across different imaging modalities. Radiologic findings are discussed according to disease stage, highlighting key diagnostic clues such as the zonal phenomenon and peripheral maturation pattern. In addition, the main entities included in the differential diagnosis are reviewed, with particular emphasis on imaging features that help distinguish myositis ossificans from soft-tissue sarcomas and other calcified or ossified lesions. Finally, current management strategies and the role of imaging in patient follow-up are summarized. A thorough understanding of the evolving imaging spectrum of myositis ossificans is essential for radiologists and clinicians to achieve an accurate diagnosis, guide appropriate management, and avoid overtreatment. Full article

Background/Objectives: Heterotopic ossification (HO), the aberrant formation of bone within soft tissues, arises either from rare genetic mutations or more commonly from traumatic insults. It is a major cause of morbidity not only in individuals harboring causative mutations, but also in those undergoing musculoskeletal surgery or trauma and in soldiers sustaining blast or burn injuries. Bone morphogenetic protein (BMP) signaling is a central driver of both hereditary and acquired forms of HO. Primary cilia are nonmotile, antenna-like organelles that extend from the cell surface and serve as crucial sensory and signaling hubs by concentrating key pathway components within a confined volume at the ciliary tip. However, their functional role in the pathogenesis of traumatic HO remains poorly understood. Methods: We investigate the role of primary cilia in traumatic HO using a genetically modified mouse model and cellular model. Results: We demonstrate that BMP signaling is attenuated when primary cilia function is disrupted. Both ciliation frequency and ciliary length were reduced in Scleraxis-CreERT2; Intraflagellar transport 88 ^{floxed/floxed} (Scx-CreERT2;Ift88^fl/fl) tenocytes. Deletion of Ift88 effectively suppressed pathological BMP signaling and inhibited HO formation. Conclusions: These findings establish that functional primary cilia are required for traumatic HO development and highlight ciliary regulation as a potential therapeutic avenue for preventing or mitigating post-traumatic HO. Full article

(1) Heterotopic ossification (HO) is a pathological process characterized by ectopic bone formation in soft tissues, often following trauma or neurological injury, and is associated with spasticity and chronic inflammation. Mesenchymal stem cells (MSCs) play a central role in HO by differentiating into osteoblasts through endochondral or intramembranous ossification, while alternative fates such as adipogenesis are suppressed. In this study, we investigated the effects of two commonly used antispastic drugs, baclofen and tizanidine, on MSC differentiation under adipogenic and inflammatory conditions in vitro. (2) Mouse C3H10T1/2 MSCs were cultured and induced toward adipogenesis in the presence of baclofen or tizanidine, and inflammatory stimuli (Interleukin-1β or lipopolysaccharides) were applied where indicated. Gene expressions of adipogenic and osteochondrogenic markers were assessed by RT-qPCR, while osteopontin protein levels were quantified by Simple Western. (3) Baclofen treatment significantly inhibited adipogenic gene expression and promoted osteochondrogenic markers and osteopontin protein under basal conditions, whereas tizanidine had minimal effects. Under inflammatory conditions, baclofen partially suppressed adipogenesis but did not strongly induce osteochondrogenesis. (4) These findings indicate that baclofen can directly modulate MSC fate, potentially contributing to HO risk, while tizanidine may offer a safer alternative for spasticity management in patients at risk of ectopic bone formation. Full article

Background: Posterior cruciate ligament reconstruction (PCLR) remains one of the most technically demanding procedures in knee ligament surgery, with complication rates considerably higher than those observed for other arthroscopic procedures. Residual laxity, arthrofibrosis, neurovascular injury, tunnel-related complications, and heterotopic ossification (HO) represent the most frequent adverse events. With increasing surgical volumes and complexity—particularly in multiligament knee injuries (MLKIs)—structured, evidence-based strategies for complication avoidance are essential. The objective of this review is to provide a comprehensive, evidence-based overview of the main complications associated with PCLR and to propose a structured, reproducible protocol for complication prevention integrating current literature and high-volume institutional experience. Methods: A narrative review of the literature was conducted using PubMed and Google Scholar to identify clinical, biomechanical, and systematic studies on PCLR complications published between 2010 and 2025. Overall, 58 studies were screened and 33 were included for qualitative synthesis. Among the included studies, the level of evidence was Level I in five systematic reviews/meta-analyses, Level III–IV in seven observational clinical studies and registries, and Level V in biomechanical studies, narrative reviews, and expert consensus reports. In parallel, the recommendations were informed by the cumulative experience of a high-volume tertiary referral center with 187 PCLR procedures performed between 2010 and 2025 (136 MLKI, 51 isolated). Results: Evidence identifies several key predictors of postoperative complications: low posterior tibial slope (<6.54°), small graft diameter (<7.0 mm), untreated posterolateral corner insufficiency, excessive tibial tunnel angle, and surgical trauma at the “killer turn.” Neurovascular complications primarily arise during tibial tunnel instrumentation, with knee hyperflexion (>90°) significantly improving safety. Suture tape augmentation (STA) reduces graft elongation by 45–58% and is associated with improved biomechanical stability without increasing complication rates. Early controlled motion is critical to prevent arthrofibrosis, whereas HO—affecting up to 45% of MLKI patients—requires delayed surgical excision after maturation. Conclusions: Optimal outcomes after PCLR derive from a structured, complication-focused approach encompassing anatomical risk assessment, meticulous tunnel planning, neurovascular protection, biological augmentation, and disciplined postoperative rehabilitation. Adoption of standardized protocols—particularly in MLKIs—can substantially reduce the incidence of adverse events and improve long-term knee stability. Full article

Background/Objectives: Neurogenic heterotopic ossification (HO) is an abnormal formation of lamellar bone in soft tissues, frequently developing near major joints in patients with spinal cord injury. While imaging provides valuable diagnostic insights, large and anatomically complex HO often requires advanced preoperative planning to minimize surgical risks. This study presents the development and clinical application of a structured six-stage workflow integrating three-dimensional (3D) technologies for the preoperative planning and surgical resection of giant iliofemoral HO. Materials and Methods: A workflow was developed comprising: (1) 3D imaging acquisition, (2) creation of a virtual model, (3) production of a life-size physical model, (4) preoperative simulation, (5) surgical resection, and (6) postoperative imaging validation. The workflow was applied to a 50-year-old male with paraplegia after a T12 fracture who developed a 26 cm iliofemoral bony bridge, confirmed by computed tomography and 3D reconstruction. Results: The physical model provided a precise anatomical reference, enabling detailed surgical rehearsal and safe planning of neurovascular dissection. Resection was performed using combined orthopedic and vascular techniques. The hip joint was preserved, and postoperative rehabilitation achieved improved range of motion and patient handling without major complications. Conclusions: This structured 3D-assisted workflow enhanced anatomical understanding and surgical precision in this complex case. The framework is applicable to other extensive ossifications with intricate anatomical relationships and warrants further evaluation in larger series. Full article

Background: Well-known risk factors for soft tissue heterotopic ossification (HO) include aging and mechanical stress, which may be linked to oxidative stress and downstream nucleotide metabolites. Thus, we investigated the involvement of extracellular ATP (ex-ATP) and its metabolites in the oxidative stress-induced mineralization of TT-D6 cells and primary mouse tendon cells. Methods: An osteogenic culture with the intermittent addition of hydrogen peroxide was monitored for two weeks using metabolomic and gene expression analyses. Results: Calcium deposition was significantly enhanced by 0.3 mM hydrogen peroxide in the osteogenic media after 2 weeks, with minimal calcification in its absence. Similar results were observed in a medium transfer experiment using 3-day-old hydrogen peroxide-treated conditioned medium, which led to an increased expression of osterix and alkaline phosphatase. Metabolomic analysis revealed a gradual increase in ex-ATP and its metabolites, including ADP, AMP, and adenosine, in the medium. The metabolite increase was enhanced by hydrogen peroxide after 12 h. Moreover, exogenous adenosine (100 μM) increased mineralization in osteogenic media. Additionally, 1 μM dipyridamole, an inhibitor of equilibrative nucleoside transporter 1 (Ent1), also increased it in response to low-dose (0.1 mM) hydrogen peroxide. Conclusions: The enhanced osteogenic calcification of the tendon cell culture by hydrogen peroxide was associated with an increase in extracellular nucleotide metabolites, especially adenosine, with some evidence of causality. Full article

Macrophages and other phagocytic cells are central regulators of tendon immunobiology, orchestrating inflammation, tissue repair, and extracellular matrix (ECM) remodeling in the tendons. They derive from circulating monocytes and resident tendon-specific populations, including tenophages. Macrophage polarization along the M1/M2 axis exerts a decisive influence on tendon healing trajectories. Activated M1 macrophages promote the early healing phase for debris clearance initiating the reparative cascade. However, their sustained activity leads to inflammation, ECM degradation, impaired healing, tendinopathy, and heterotopic ossification (HO). Conversely, a timed shift toward activated M2 macrophages promotes resolution of inflammation, angiogenesis, ECM deposition, and fibrocartilage formation, whereas excessive or prolonged M2 activity facilitates adhesion formation, fibrosis, scarring and HO. Recent single-cell and spatial profiling studies showed macrophage heterogeneity across tendon compartments, thereby extending the classical M1/M2 paradigm and underscoring the relevance of macrophages/resident tendon cell’s interaction in tendon-specific local niches. Mechanobiological stimuli (depending on magnitude, frequency and duration) further modulate macrophage phenotypes and tendon healing. Emerging coculture models and human tendon-on-chip systems provide high-resolution platforms for dissecting these spatiotemporal interactions. Promising therapeutic approaches comprise the application of extracellular vesicles, controlled mechanoloading regimens, and immunomodulatory biomaterials demonstrating potential to induce regenerative macrophage signatures for improved healing outcomes. Notably, platelet-rich plasma (PRP) formulations shape macrophage responses: leukocyte-rich PRP preferentially promotes M1 activity whereas leukocyte-poor PRP supports M2 polarization. Thus, mechano- and immunomodulatory strategies can offer precise control over macrophage dynamics. Regarding the Achilles tendon pathologies, such approaches are helpful by directing macrophage-mediated inflammation towards effective tendon healing outcomes. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) is widely used for small lung tumors, but the physics of electron transport in low-density lungs remains incompletely understood. This study quantifies the effect of lung density on dosimetry for small lesions. Methods: To study the dosimetric parameters a pseudo patient option was chosen. A lung SBRT patient with a central lesion was modeled in the Eclipse treatment planning system using the AAA algorithm. Three target sizes (1.0, 1.5, and 2.0 cm) were planned with lung densities overridden from 0.1 to 1.0 g/cm³. Standard SBRT constraints were applied, and dosimetry indices (CI, HI, GI), maximum dose, and MU/Gy were recorded to see the pattern. Results: Dose–volume histograms (DVHs) showed marked dependence on both lesion size and lung density. Lower densities produced higher maximum doses (up to 135% at 0.1 g/cm³), steeper DVH tails, and significantly increased MU/Gy. Conformity was achievable in all cases, but at the cost of degraded homogeneity and gradient indices. At higher density (1.0 g/cm³), maximum dose values fell to 108–110% which is typical in non-lung cases. Conclusions: SBRT planning in low-density lungs requires substantially higher MU and results in greater dose spillage despite acceptable conformity. These findings highlight the importance of considering density effects when comparing clinical outcomes across institutions and selecting optimal plans, where minimizing MU/Gy may reduce unnecessary dose burden. Full article

Background and Objectives: Short femoral stems are increasingly used in total hip arthroplasty (THA), yet evidence regarding their performance in elderly femoral neck fracture (FNF) patients is limited. In this study, we compared clinical and radiographic outcomes of the use of a short femoral stem (SFS) versus a conventional standard stem (CSS) in cementless THA. Materials and Methods: This prospective, single-center case–control study (1:2) included patients ≥ 65 years of age with displaced FNF (Garden 3–4) treated with cementless THA. Follow-up lasted a minimum of 2 years. Clinical evaluations included the Harris Hip Score (HHS), Roles and Maudsley satisfaction score, and thigh pain assessment. Radiographic evaluations assessed cup position, osseointegration (Moore signs), radiolucencies (DeLee–Charnley and Gruen zones), subsidence, leg length discrepancy (LLD), and heterotopic ossification. Results: A total of 114 patients were analyzed (38 with SFS versus 76 with CSS). The final follow-up HHS was 87 ± 2.7 (SFS) and 88 ± 2.5 (CSS) (p = 0.231), and satisfaction was excellent in nearly all patients in both groups. Thigh pain was rare and resolved by final follow-up in all SFS patients, and no radiographic loosening was observed. Early subsidence (≤3 mm) occurred in two SFSs and three CSSs without progression, while LLD < 1 cm was present in three SFS and eight CSS cases. No implant-related revisions occurred, and complication rates were low and comparable. Conclusions: Short femoral stems provided clinical and radiographic outcomes equivalent to those of conventional stems in elderly FNF patients treated with cementless THA. Short stems appear to be a safe and effective option in this population, and further studies with longer follow-up are needed to confirm their durability. Full article

Background/Objectives: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic bone disorder, leading to progressive immobilization through the formation of bone in muscles, tendons, and ligaments. A variant in the ACVR1 gene results in a constitutively overactive ALK2 receptor, leading to the aberrant activation of the SMAD1/5/9 pathway. This activation occurs not only in response to Activin A, which does not normally activate this pathway, but also through heightened sensitivity to BMP ligands and even in the absence of ligand binding. This dysregulated signaling ultimately drives the formation of heterotopic ossification. The inhibition of the altered ALK2 receptor holds promise as a potential treatment strategy that is currently being investigated in several trials. In this study, we performed an in vitro characterization of novel kinase inhibitor KTI-2338 with high selectivity for the ALK2 receptor. Methods: Dermal human FOP and control fibroblasts were cultured in osteogenic medium with and without the inhibitor to assess the effect on transdifferentiation into osteoblast-like cells. Results: Compound KTI-2338 elicited effects consistent with inhibiting aberrant Activin A signaling and receptor sensitization, through reductions in osteogenic markers and pSMAD1/5/9 expression levels. In line with this, a pattern of reduced Alizarin Red staining was observed following treatment with the compound, indicating reduced mineralization. Conclusions: These findings indicate that kinase inhibitor KTI-2338 disrupts the pathological processes underlying FOP and may offer a new therapeutic option for this devastating disease. Full article

A traumatic elbow dislocation that remains unreduced for more than three weeks is considered a neglected elbow dislocation. We report a case of a patient with a neglected elbow dislocation combined with a terrible triad injury (elbow dislocation with fractures of the coronoid process and radial head). Initially, the patient was managed with three weeks of cast immobilization followed by physiotherapy. However, six months after the trauma, he presented to our clinic with severe heterotopic ossification, significant pain, and nearly complete elbow stiffness. An open surgical intervention was performed, involving excision of the heterotopic bone, reduction in the dislocation, and suturing of the anterior capsule to the coronoid process. Given the irreparable fracture of the radial head, radial head arthroplasty was also performed. At 18-month follow-up, the elbow was stable and pain-free, with flexion–extension of 80°, pronation of 85°, and supination of 80°. This case underscores the critical importance of early diagnosis and intervention to prevent long-term complications in neglected elbow dislocations. Full article