Many risk factors for osteoarthritis (OA) have been noted, while gender/sex differences have been understated. The work aimed to systematically review literature investigating as primary aim the relationship between gender/sex related discriminants and OA. The search was performed in PubMed, Science Direct and Web of Knowledge in the last 10 years. Inclusion criteria were limited to clinical studies of patients affected by OA in any joints, analyzing as primary aim gender/sex differences. Exclusion criteria were review articles, in vitro, in vivo and ex vivo studies, case series studies and papers in which gender/sex differences were adjusted as confounding variable. Of the 120 records screened, 42 studies were included. Different clinical outcomes were analyzed: morphometric differences, followed by kinematics, pain, functional outcomes after arthroplasty and health care needs of patients. Women appear to use more health care, have higher OA prevalence, clinical pain and inflammation, decreased cartilage volume, physical difficulty, and smaller joint parameters and dimensions, as compared to men. No in-depth studies or mechanistic studies analyzing biomarker differential expressions, molecular pathways and omic profiles were found that might drive preclinical and clinical research towards sex-/gender-oriented protocols.

Osteoarthritis (OA) is a highly prevalent joint disease that primarily affects about 10% of the world’s population over 60 years old. The purpose of this study is to systematically review the preclinical studies regarding sex differences in OA, with particular attention to the molecular aspect and gene expression, but also to the histopathological aspects. Three databases (PubMed, Scopus, and Web of Knowledge) were screened for eligible studies. In vitro and in vivo papers written in English, published in the last 11 years (2009–2020) were eligible. Participants were preclinical studies, including cell cultures and animal models of OA, evaluating sex differences. Independent extraction of articles and quality assessments were performed by two authors using predefined data fields and specific tools (Animals in Research Reporting In Vivo Experiments (ARRIVE) guideline and Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool). Twenty-three studies were included in the review: 4 in vitro studies, 18 in vivo studies, and 1 both in vitro and in vivo study. From in vitro works, sex differences were found in the gene expression of inflammatory molecules, hormonal receptors, and in responsiveness to hormonal stimulation. In vivo research showed a great heterogeneity of animal models mainly focused on the histopathological aspects rather than on the analysis of sex-related molecular mechanisms. This review highlights that many gaps in knowledge still exist; improvementsin the selection and reporting of animal models, the use of advanced in vitro models, and multiomics analyses might contribute to developing a personalized gender-based medicine.

Osteoporosis (OP) is one of the most significant causes of morbidity, particularly in post-menopausal women and older men. Despite its remarkable occurrence, the search for an effective treatment is still an open challenge. Here, we systematically reviewed the preclinical and clinical progress in the development of nano-based materials as drug delivery systems against OP, considering the effects on bone healing and regeneration, the more promising composition and manufacturing methods, and the more hopeful drugs and delivery methods. The results showed that almost all the innovative nano-based delivery systems developed in the last ten years have been assessed by preclinical investigations and are still in the preliminary/early research stages. Our search strategy retrieved only one non-randomized controlled trial (RCT) on oligosaccharide nanomedicine of alginate sodium used for degenerative lumbar diseases in OP patients. Further investigations are mandatory for assessing the clinical translation and commercial purposes of these materials. To date, the main limits for the clinical translation of nano-based materials as drug delivery systems against OP are probably due to the low reproducibility of the manufacturing processes, whose specificity and complexity relies on an adequate chemical, structural, and biomechanical characterization, as the necessary prerequisite before assessing the efficacy of a given treatment or process. Finally, an unsatisfactory drug-loading capacity, an uncontrollable release kinetic, and a low delivery efficiency also limit the clinical application.

A systematic review on in vitro 3d bone metastases models. A new horizon to recapitulate the native clinical scenario?

Enhanced recovery after surgery (ERAS) protocols have led to improvements in outcomes in several surgical fields, through multimodal optimization of patient pathways, reductions in complications, improved patient experiences and reductions in the length of stay. However, their use has not been uniformly recognized in all orthopedic fields, and there is still no consensus on the best implementation process. Here, we evaluated pre-, peri-, and post-operative key elements and clinical evidence of ERAS protocols, measurements, and associated outcomes in patients undergoing different orthopedic surgical procedures. A systematic literature search on PubMed, Scopus, and Web of Science Core Collection databases was conducted to identify clinical studies, from 2012 to 2022. Out of the 1154 studies retrieved, 174 (25 on spine surgery, 4 on thorax surgery, 2 on elbow surgery and 143 on hip and/or knee surgery) were considered eligible for this review. Results showed that ERAS protocols improve the recovery from orthopedic surgery, decreasing the length of hospital stays (LOS) and the readmission rates. Comparative studies between ERAS and non-ERAS protocols also showed improvement in patient pain scores, satisfaction, and range of motion. Although ERAS protocols in orthopedic surgery are safe and effective, future studies focusing on specific ERAS elements, in particular for elbow, thorax and spine, are mandatory to optimize the protocols.

Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components.