20 research outputs found
The Genetic and Biological Basis of Pseudoarthrosis in Fractures: Current Understanding and Future Directions
No full textPseudoarthrosis—the failure of normal fracture healing—remains a significant orthopedic challenge affecting approximately 10–15% of long bone fractures, and is associated with significant pain, prolonged disability, and repeated surgical interventions. Despite extensive research into the pathophysiological mechanisms of bone healing, diagnostic approaches remain reliant on clinical findings and radiographic evaluations, with little innovation in tools to predict or diagnose non-union. The present review evaluates the current understanding of the genetic and biological basis of pseudoarthrosis and highlights future research directions. Recent studies have highlighted the potential of specific molecules and genetic markers to serve as predictors of unsuccessful fracture healing. Alterations in mesenchymal stromal cell (MSC) function, including diminished osteogenic potential and increased cellular senescence, are central to pseudoarthrosis pathogenesis. Molecular analyses reveal suppressed bone morphogenetic protein (BMP) signaling and elevated levels of its inhibitors, such as Noggin and Gremlin, which impair bone regeneration. Genetic studies have uncovered polymorphisms in BMP, matrix metalloproteinase (MMP), and Wnt signaling pathways, suggesting a genetic predisposition to non-union. Additionally, the biological differences between atrophic and hypertrophic pseudoarthrosis, including variations in vascularity and inflammatory responses, emphasize the need for targeted approaches to management. Emerging biomarkers, such as circulating microRNAs (miRNAs), cytokine profiles, blood-derived MSCs, and other markers (B7-1 and PlGF-1), have the potential to contribute to early detection of at-risk patients and personalized therapeutic approaches. Advancing our understanding of the genetic and biological underpinnings of pseudoarthrosis is essential for the development of innovative diagnostic tools and therapeutic strategies
A 3D-printed load sharing implant achieved union of a 9-cm femoral segmental bone defect within three months using a hybrid Masquelet induction membrane technique. A case-report
No full textCase: A 30-year-old male was admitted in our hospital having an open left distal femoral fracture with 9-cm segmental bone defect and a closed proximal left tibial fracture. He was treated successfully using a Hybrid (Titanium Cage and Bone Graft) Masquelet Induction Membrane Technique (MIMT). His femoral fracture united 3-months post - operatively. The left tibia was treated initially with two locking plates. Following infection, a 3-cm tibial bone gap was treated with external fixation and conventional MIMT. The tibial fracture united 12-months post- operatively. Conclusion: The Hybrid MIMT achieved a successful healing outcome in this challenging case. © 2024 The Author(s
Revision of distal femoral endoprosthetic arthroplasty with impacted morsellized allograft
No full textThe purpose of this study was to review the clinical results of irradiated fresh frozen osteochondral allografts for large osteochondral defects of the knee using the Mega-OATS technique
Liquid Biopsy: A New Translational Diagnostic and Monitoring Tool for Musculoskeletal Tumors
No full textSoft tissue and bone sarcomas represent a group of aggressive neoplasms often accompanied by dismal patient prognosis, especially when distant metastases are present. Moreover, effective treatment can pose a challenge, as recurrences are frequent and almost half of patients present with advanced disease. Researchers have unveiled the molecular abnormalities implicated in sarcomas’ carcinogenesis, paving the way for novel treatment strategies based on each individual tumor’s characteristics. Therefore, the development of new techniques aiding in early disease detection and tumor molecular profiling is imperative. Liquid biopsy refers to the sampling and analysis of patients’ fluids, such as blood, to identify tumor biomarkers, through a variety of methods, including qRT-PCR, qPCR, droplet digital PCR, magnetic microbeads and digital PCR. Assessment of circulating tumor cells (CTCs), circulating free DNA (ctDNA), micro RNAs (miRs), long non-coding RNAs (lncRNAs), exosomes and exosome–associated proteins can yield a plethora of information on tumor molecular signature, histologic type and disease stage. In addition, the minimal invasiveness of the procedure renders possible its wide application in the clinical setting, and, therefore, the early detection of the presence of tumors. In this review of the literature, we gathered information on biomarkers assessed through liquid biopsy in soft tissue and bone sarcoma patients and we present the information they can yield for each individual tumor type
Class II Phosphoinositide 3-Kinases Contribute to Endothelial Cells Morphogenesis
No full textPMCID: PMC3539993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
The EPH/Ephrin System in Bone and Soft Tissue Sarcomas’ Pathogenesis and Therapy: New Advancements and a Literature Review
No full textMusculoskeletal sarcomas represent rare heterogenous malignancies of mesenchymal origin that can be divided in two distinct subtypes, bone and soft tissue sarcomas. Current treatment options combine the surgical excision of local tumors and multidrug chemotherapy to prevent metastatic widespread disease. Due to the grim prognosis that usually accompanies such tumors, researchers have attempted to shed light on the molecular pathways implicated in their pathogenesis in order to develop novel, innovative, personalized therapeutic strategies. Erythropoietin-producing human hepatocellular receptors (EPHs) are tyrosine-kinase transmembrane receptors that, along with their ligands, ephrins, participate in both tumor-suppressive or tumor-promoting signaling pathways in bone and soft tissue sarcomas. The EPH/ephrin axis orchestrates cancerous processes such as cell–cell and cell–substrate adhesion and enhances the remodeling of the intracellular cytoskeleton to stimulate the motility and invasiveness of sarcoma cells. The purpose of our study was to review published PubMed literature to extract results from in vitro, in vivo and clinical trials indicative of the role of EPH/ephrin signaling in bone and soft tissue sarcomas. Based on these reports, significant interactions between the EPH/ephrin signaling pathway and a plethora of normal and abnormal cascades contribute to molecular mechanisms enhancing malignancy during sarcoma progression. In addition, EPHs and ephrins are prospective candidates for diagnostic, monitoring and therapeutic purposes in the clinical setting against bone and soft tissue sarcomas
The anti-neoplastic effect of doxycycline in osteosarcoma as a metalloproteinase (MMP) inhibitor: a systematic review
No full textBackground Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of diagnosis. Surgical resection with neoadjuvant and adjuvant therapies improves the overall and disease-free survival of patients. Doxycycline, a synthetic tetracycline, has been found to act either as an antibiotic drug or as a chemotherapeutic agent. Its anti-neoplastic role has been found to be significant, in vitro and in vivo laboratory trials, in various types of cancer, such as prostate, intestinal, central neural system cancers and osteosarcoma. Inhibition of metalloproteinases (MMPs) in different stages of tumour expansion is the most well-understood mechanism. MMPs are secreted molecules from various normal cells, such as fibroblasts, leucocytes and vascular smooth muscles, as well as from cells with high proliferative potential, such as tumour cells. In osteosarcoma, MMPs have been found to be overexpressed. MMPs help osteosarcoma cells survive, grow and produce metastases in distant sites, mainly in the lungs. Doxycycline blocks extracellular matrix and basic membrane degradation by suppressing MMP function. As a consequence, osteosarcoma cells lose their ability to invade and metastasize. Additionally, doxycycline eliminates the secretion of vascular endothelial growth factor (VEGF) and deprives the supply of circulating nutrients by its anti-angiogenesis action. The aim of this review is to evaluate doxycycline's action against osteosarcoma cells as an MMP-inhibitor and interpret its usage as a chemotherapeutic agent. Methods We checked PubMed and Google Scholar for recently published data, on the tumour-supportive role of MMPs and VEGF in osteosarcoma cells. We further studied published experimental trials on the role of doxycycline as a tumour-suppressive agent via MMPs and VEGF inhibition. Results MMPs and VEGF have been found to play a fundamental role in osteosarcoma cells survival and high aggressiveness by in vitro, in vivo and clinical trials. Nevertheless, doxycycline has proved its tumour-suppressive effect by in vivo experimental trials in various cancers but not yet in osteosarcoma. Conclusion Doxycycline remains a promising chemotherapeutic agent against osteosarcoma via MMP inhibition, showing the need for further in vivo and clinical trials to be carried out in the future
Rare diseases of bone: Erdheim-Chester and Rosai-Dorfman non-Langerhans cell histiocytoses
No full text▪ Non-Langerhans cell histiocytosis (N-LCH) summarizes a group of rare diseases with different clinical presentations, pathogenesis and morphology. These include primary cutaneous N-LCH, cutaneous N-LCH with systemic involvement, and primary extracutaneous systemic forms with occasional cutaneous involvement. ▪ The juvenile (JXG) and non-juvenile xanthogranuloma (N-JXG) family of histiocytoses are N-LCH: the JXG family consisting of the JXG (cutaneous), xanthoma disseminatum (cutaneous and systemic) and Erdheim-Chester disease (ECD; systemic); and the N-JXG family consisting of the solitary reticulohistiocytoma (cutaneous), multicentric reticulohistiocytosis (cutaneous and systemic) and Rosai- Dorfman disease (RDD; systemic). ▪ ECD is a clonal disorder from the JXG family of N-LCH; RDD is a reactive proliferative entity from the non-juvenile xanthogranuloma family of N-LCH. ▪ ECD and RDD N-LCH are rare disorders, which are difficult to diagnose, with multi-organ involvement including bone and systemic symptoms, and which respond to therapy in an unpredictable way. ▪ The key to successful therapy is accurate identification at tissue level and appropriate staging. Patients should be observed and monitored in a long-term pattern. Prognosis depends on disease extent and the organs involved; it is generally good for RDD disease and variable for ECD. © 2018 The author(s)
