Novel directions in the study of osteoporosis: focus on gut microbiota as a potential therapeutic target.

Osteoporosis is a significant social health problem, not only in terms of pain and disability but also in terms of mortality rate. In recent years, there is an increasing interest in studying the relationship between gut dysmicrobiosis, immune system and bone health, therefore the term "osteomicrobiology" has been recently coined. This review aims to summarize the current knowledge about the link between gut dysbiosis and osteoporosis, in order to define a potential preventive and therapeutic strategy. Gut microbiota (GM) plays a major role in maintaining body homeostasis, since it is involved in several physiological processes; in recent years, the gut microbiota has shown to modulate not only local processes but also systemic responses including bone metabolism. Several potential mechanisms may explain how gut microorganisms could affect bone metabolism, i.e. influencing the host metabolism, immune system and hormone secretion. The relationship between gut dysbiosis, immunological dysfunction and bone loss could be explained by mainly focusing on T cells. Moreover, it should be noted that the relationship between GM and the endocrine system could also explicate how the microbiome influences bone status. In this context, Insulin-Like Growth Factor-1 (IGF-1), vitamin D, serotonin and leptin might play a central role. GM could have a significant impact on bone metabolism, therefore future clinical studies are necessary to develop a new multidisciplinary approach for osteoporosis treatment and prevention.

The limits and potentials of presepsin in orthopaedic surgery: state of the art and future directions.

Presepsin, i.e. the soluble cluster of differentiation 14-SubType (sCD14-ST), is an emerging biomarker for the diagnosis and evaluation of sepsis and infection. In 2004, Yaegashi et al. originally described presepsin as a potential biomarker; since then, several studies have investigated the role of presepsin in different infectious conditions, including neonatal sepsis, severe acute pancreatitis, infections in patients with haematological malignancies, severe community-acquired pneumonia, pacemaker and implantable cardioverter-defibrillator (ICD) pocket infections, surgical site infections (SSIs) and periprosthetic joint infects (PJIs). Moreover, presepsin has been also studied in the risk stratification in cardiac surgery patients, and as a biomarker in the perioperative management of patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). This review aims to summarize the current knowledge about presepsin, focusing on the limits and potentials that the use of this biomarker could have in daily clinical practice. Presepsin is could be useful in daily clinical practice in orthopaedic surgery in the diagnosis and prevention of SSIs and PJIs. It is a cost-effective biomarker, but to improve its accuracy, it is important to carefully recalculate presepsin circulating values in patients with chronic kidney disease. However, further studies with larger patients' samples are needed to better validate the use of this biomarker in orthopaedics. In the future, synovial fluid presepsin might be a useful biomarker in the diagnosis of septic arthritis and PJIs.

Humeral shaft butterfly fractures managed with intramedullary nail: could the third fragment features predict the fracture healing time?

To assess the impact of the radiological features of the third fragment on the outcome of humeral shaft fractures type 12-B managed with endomedullary nails. We retrospectively evaluated a series of 80 patients, divided into 3 groups, according to the fracture healing time: within 6 months (group-A), between 6 and 12 months (group-B) or fracture non-union after 12 months (group-C). In 26 patients out of 80 the fracture healing was observed at 6 months follow-up; in 47 out of 80 at 12 months after trauma and in 7 out of 80 no fracture healing was observed at 12 months follow-up. Regression analysis showed that the third fragment displacement and angulation are the most important features that affect the fracture healing. The mean third fragment dislocation (cut-off: 12 mm) is the main parameter to influence the fracture healing within or in more than six months.

New insights into the treatment of non-healing diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes mellitus, affecting about 15% of diabetic patients. This review describes the innovative treatment options currently available in the treatment of non-healing DFUs. The use of Platelet-Rich-Plasma (PRP) is a safe and valid approach in the treatment of DFUs. However, the methods used to obtain and prepare autologous PRP vary between the studies, thus further evidences are eagerly awaited. Adipose tissue-derived mesenchymal stem cells (ADSCs) are a promising tool in the treatment of DFUs, but additional largescale and long-term follow-up clinical trials are needed. Bone marrow mesenchymal stem cells (BM-MSCs) transplantation, on the other hand, revealed effective in reducing incidents and improving the quality of life of patients with amputations. Autologous Peripheral Blood Mononuclear Cells (A-PBMNCs) showed a good efficacy in the treatment of diabetic patients with CLI, but further RCTs are awaited to best investigate this new therapeutic approach. Photobiomodulation (PBM) therapy revealed effective in the treatment of DFUs in two RCTs, but a standardization of therapeutic protocols as well as level-I studies are needed.

Biophysical stimulation of the knee with PEMFs: from bench to bedside.

Clinical biophysics investigates the relationship between non-ionizing physical energy and the human body. Although several types of electrical stimulation devices have received US FDA approval for orthopaedic application, the use of Pulsed Electromagnetic Field (PEMFs) play a central role in joint biophysics. This narrative review aims to summarize the current evidences on the efficacy of PEMF-therapy in the treatment of knee articular diseases. Preclinical studies have assessed the effects of PEMFs on chondrocytes, synoviocytes, articular cartilage explants and animal models, showing positive effects of PEMF-therapy on cells proliferation, extracellular matrix (ECM) production, chondrocytes apoptosis and inflammatory cytokines down-regulation. Currently, PEMF-therapy is a valid option in the conservative management of several knee articular diseases, including early OA, patellofemoral pain syndrome and SONK. PEMFs could be also used as an adjunct after an arthroscopic knee procedure or TKA implantation, in order to control the joint post-operative inflammatory state.