PTX3 Effects on Osteogenic Differentiation in Osteoporosis: An In Vitro Study

Pentraxin 3 (PTX3) is a glycoprotein belonging to the humoral arm of innate immunity that participates in the body's defence mechanisms against infectious diseases. It has recently been defined as a multifunctional protein, given its involvement in numerous physiological and pathological processes, as well as in the pathogenesis of age-related diseases such as osteoporosis. Based on this evidence, the aim of our study was to investigate the possible role of PTX3 in both the osteoblastic differentiation and calcification process: to this end, primary osteoblast cultures from control and osteoporotic patients were incubated with human recombinant PTX3 (hrPTX3) for 72 h. Standard osteinduction treatment, consisting of beta-glycerophosphate, dexamethasone and ascorbic acid, was used as control. Our results showed that treatment with hrPTX3, as well as with the osteogenic cocktail, induced cell differentiation towards the osteoblastic lineage. We also observed that the treatment not only promoted an increase in cell proliferation, but also the formation of calcification-like structures, especially in primary cultures from osteoporotic patients. In conclusion, the results reported here suggest the involvement of PTX3 in osteogenic differentiation, highlighting its osteoinductive capacity, like the standard osteoinduction treatment. Therefore, this study opens new and exciting perspectives about the possible role of PTX3 as biomarker and therapeutic agent for osteoporosis

Leg fracture associated with synostosis of interosseous membrane during running in a soccer player

ntroduction - Leg fractures may occur frequently in sport injuries but it is very rare to find this kind of injury associated with interosseous membrane synostosis. This case report describes a unique case of 42 B1.2 fracture of the leg associated with an interosseous membrane synostosis and literature review on Pubmed, Google scholar and Medscape. Case Presentation - A 26 year old male amateur soccer player came to our attention at the emergency room after a fall while he was running without any direct trauma following a referred ankle sprain. X-ray and CT scan of the left leg showed a comminuted displaced fracture of the lower middle third of tibial and peroneus diaphysis, and moreover, a fracture of peroneal malleolus associated with a bone bridge between the tibia and fibula. The patient was treated with a surgical osteosynthesis the day after trauma. Conclusion - We think that the interosseous membrane plays an important role in biomechanics of the leg even during running. To our knowledge, this is the first case reported which show the fractures of the tibia and fibula associated with an ipsilateral synostosis of the interosseous membrane. Class of evidence: Level V

Osteosarcopenia and Pain: Do We Have a Way Out?

osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. for patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting the individual's functionality and promoting disability, it has a huge psychological burden involving anxiety, depression, and social withdrawal. unfortunately, the molecular mechanisms involved in the development and persistence of pain in OSP have not yet been fully elucidated, although immune cells are known to play a key role in these processes. Indeed, they release several molecules that promote persistent inflammation and nociceptive stimulation, resulting in the gating of ion channels responsible for the generation and propagation of the noxious stimulus. the adoption of countermeasures to counteract the OSP progression and reduce the algic component appears to be necessary, providing patients with a better quality of life and greater adherence to treatment. In addition, the development of multimodal therapies, based on an interdisciplinary approach, appears to be crucial, combining the use of anti-osteoporotic drugs with an educational programme, regular physical activity, and proper nutrition to eliminate risk factors. based on this evidence, we conducted a narrative review using the pubmed and google scholar search engines to summarize the current knowledge on the molecular mechanisms involved in the pain development in OSP and the potential countermeasures to be taken. the lack of studies addressing this topic highlights the need to conduct new research into the resolution of an ever-expanding social problem

Sarcopenia and bone health: new acquisitions for a firm liaison

Osteosarcopenia (OS) is a newly defined condition represented by the simultaneous presence of osteopenia/osteoporosis and sarcopenia, the main age-related diseases. The simultaneous coexistence of the two phenotypes derives from the close connection of the main target tissues involved in their pathogenesis: bone and muscle. These two actors constitute the bone-muscle unit, which communicates through a biochemical and mechanical crosstalk which involves multiple factors. Altered pattern of molecular pathways leads to an impairment of both the functionality of the tissue itself and the communication with the complementary tissue, composing the OS pathogenesis. Recent advances in the genetics field have provided the opportunity to delve deeper into the complex biological and molecular mechanisms underlying OS. Unfortunately, there are still many gaps in our understanding of these pathways, but it has proven essential to apply strategies such as exercise and nutritional intervention to counteract OS. New therapeutic strategies that simultaneously target bone and muscle tissue are limited, but recently new targets for the development of dual-action drug therapies have been identified. This narrative review aims to provide an overview of the latest scientific evidence associated with OS, a complex disorder that will pave the way for future research aimed at understanding the bone-muscle-associated pathogenetic mechanisms

Ascorbic acid reduces Ropivacaine-induced myotoxicity in cultured human osteoporotic skeletal muscle cells

Background: Osteoporosis is a worldwide health issue. Loss of bone mass is a potential risk factor for fragility fractures, and osteoporotic fractures place a considerable burden on society. Bone and muscle represent a functional unit in which the two tissues are intimately interconnected. Ropivacaine is a potent local anesthetic used in clinical practice for intraoperative anesthesia and postoperative pain management, in particular for hip surgery. When injected, Ropivacaine can diffuse locally through, in particular in surrounding skeletal muscle tissue, causing dose-dependent cytotoxicity, oxidative stress and myogenesis impairment. Based on those evidences, we focused our attention on Ropivacaine-induced cytotoxicity on cultured human myoblasts. Methods: Primary human myoblasts and myotubes from healthy subjects, osteoarthritic and osteoporotic patients (OP) were cultured in the presence of Ropivacaine. In some experiments, ascorbic acid (AsA) was added as a potent antioxidant agent. Cell viability and ROS levels were evaluated to investigate the myotoxic activity and Real-Time PCR and Western blot analysis carried out to investigate the expression of proliferation and myogenic markers. Results: A dose-dependent decrease of cell viability was observed after Ropivacaine exposure in both OP myoblasts and myotubes cultures, whereas those effects were not observed in the presence of Propofol, a general anesthetic. The adding of AsA reduced Ropivacaine negative effects in OP myoblast cultures. In addition, Ropivacaine exposure also increased ROS levels and upregulated Nox4 expression, an enzyme primarily implicated in skeletal muscle ROS generation. AsA treatment counteracted the oxidant activity of Ropivacaine and partially restored the basal condition in cultures. Positive myogenic markers, such as MyoD and Myf5, were downregulated by Ropivacaine exposure, whereas myostatin, a negative regulator of muscle growth and differentiation, was upregulated. The phenotypic deregulation of myogenic controllers in the presence of Ropivacaine was counteracted by AsA treatment. Conclusions: Our findings highlight the oxidative stress-mediated myotoxic effect of Ropivacaine on human skeletal muscle tissue cell cultures, and suggest treatment with AsA as valid strategy to mitigate its negative effects and allowing an ameliorated functional skeletal muscle recovery in patients undergoing hip replacement surgery for osteoporotic bone fracture

Fragility fractures of the pelvis: treatment and preliminary results

With increasing life expectancy, fragility fractures of the pelvic ring (FFP) are becoming frequent. In elderly, osteoporosis leads to a decrease of bone strength and resistance to the ligament's traction; this represents the most important difference between FFP and fractures in young patients. Usually, these fractures are underestimated and treatment is often conservative

Hip replacement in femoral neck fractures: the role of cementation and its technical difficulties

Hip fractures in elderly patients are an arising problem due to aging of population and still represent a controversial challenge for orthopedic surgeon who should help achieve the best functional recovery in the shortest time. Cementation in hip replacement plays an important role, but it should be carefully planned considering the possible risks. According to the literature, there are still no certainties regarding the superiority of an uncemented implant compared to a cemented one. The purpose of this work is to conduct an overview of the scientific literature that can clarify the advantages and disadvantages of cemented and non-cemented implants from a biological and biomechanical point of view

State of fragility fractures management during the COVID-19 pandemic

Osteoporosis is a public health concern all over the world. As a chronic condition, it generally requires prolonged medical interventions to limit the risks of further bone loss, impaired skeletal integrity and the onset of fractures. This problem is further complicated by the fact that the abrupt cessation of some therapies may be associated with an increased risk of harm. It is in this context that the COVID-19 pandemic has caused an unprecedented disruption to the provision of healthcare worldwide, exceeding our worst expectations in terms of the number of lives lost and the rapidity at which consolidated economies and healthcare systems are being significantly damaged. In this review, we assessed the challenges and strategies used in the management of osteoporosis and fragility fracture care during the COVID-19 pandemic. We also examined the available evidence and provided clinical recommendations that will require reassessment as the worldwide response to COVID-19 evolves

Chronic Pain in Musculoskeletal Diseases: Do You Know Your Enemy?

Musculoskeletal pain is a condition that characterises several diseases and represents a constantly growing issue with enormous socio-economic burdens, highlighting the importance of developing treatment algorithms appropriate to the patient’s needs and effective management strategies. Indeed, the algic condition must be assessed and treated independently of the underlying pathological process since it has an extremely negative impact on the emotional and psychic aspects of the individual, leading to isolation and depression. A full understanding of the pathophysiological mechanisms involved in nociceptive stimulation and central sensitization is an important step in improving approaches to musculoskeletal pain. In this context, the bidirectional relationship between immune cells and neurons involved in nociception could represent a key point in the understanding of these mechanisms. Therefore, we provide an updated overview of the magnitude of the musculoskeletal pain problem, in terms of prevalence and costs, and summarise the role of the most important molecular players involved in the development and maintenance of pain. Finally, based on the pathophysiological mechanisms, we propose a model, called the “musculoskeletal pain cycle”, which could be a useful tool to counteract resignation to the algic condition and provide a starting point for developing a treatment algorithm for the patient with musculoskeletal pain