Osteoarthritis is a degenerative joint disease affecting middle-aged and elderly patients. It mainly involves weight-bearing joints such as the hip, knee and spine as well as the basilar joint of the thumb, causing dysfunction and painful symptoms. Often, joint arthritis is accompanied by cartilage defects, joint space narrowing, osteophytes, bone sclerosis and subchondral bone cysts (SBC). The aim of the present study was to explore the pathophysiology responsible for the development of SBCs as well as the association between SBCs and disease progress, the level of clinical symptoms and their impact on postoperative outcomes and risk of possible complications following joint replacements if left untreated. A literature review on PubMed articles was conducted to retrieve and evaluate all available evidence related to the main objective mentioned above. A few theories have been put forth to explain the formation process of SBCs. These involve MMPs secretion, angiogenesis, and enhanced bone turnover as a biological response to abnormal mechanical loads causing repeated injuries on cartilage and subchondral tissue during the development of arthritis. However, the application of novel therapeutics, celecoxib-coated microspheres, local administration of IGF-1 and activated chondrocytes following surgical debridement of SBCs hinders the expansion of SBCs and prevents the progression of osteoarthritis.

Background: 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.

Neurofibromatosis type 1 (NF1), which is the most common phacomatoses, is an autosomal dominant disorder characterized by clinical presentations in various tissues and organs, such as the skin, eyes and nervous and skeletal systems. The musculoskeletal implications of NF1 include a variety of deformities, including scoliosis, kyphoscoliosis, spondylolistheses, congenital bony bowing, pseudarthrosis and bone dysplasia. Scoliosis is the most common skeletal problem, affecting 10–30% of NF1 patients. Although the pathophysiology of spinal deformities has not been elucidated yet, defects in bone metabolism have been implicated in the progression of scoliotic curves. Measurements of Bone Mineral Density (BMD) in the lumbar spine by using dual energy absorptiometry (DXA) and quantitative computer tomography (QCT) have demonstrated a marked reduction in Z-score and osteoporosis. Additionally, serum bone metabolic markers, such as vitamin D, calcium, phosphorus, osteocalcin and alkaline phosphatase, have been found to be abnormal. Intraoperative and histological vertebral analysis confirmed that alterations of the trabecular microarchitecture are associated with inadequate bone turnover, indicating generalized bone metabolic defects. At the molecular level, loss of function of neurofibromin dysregulates Ras and Transforming Growth factor-β1 (TGF-β1) signaling and leads to altered osteoclastic proliferation, osteoblastic activity and collagen production. Correlation between clinical characteristics and molecular pathways may provide targets for novel therapeutic approaches in NF1.

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I² = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

Soft 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.

Musculoskeletal 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.