Epigenetics in Knee Osteoarthritis: A 2020-2023 Update Systematic Review.

Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation.

Machine learning algorithms distinguish discrete digital emotional fingerprints for web pages related to back pain.

Back pain is the leading cause of disability worldwide. Its emergence relates not only to the musculoskeletal degeneration biological substrate but also to psychosocial factors; emotional components play a pivotal role. In modern society, people are significantly informed by the Internet; in turn, they contribute social validation to a "successful" digital information subset in a dynamic interplay. The Affective component of medical pages has not been previously investigated, a significant gap in knowledge since they represent a critical biopsychosocial feature. We tested the hypothesis that successful pages related to spine pathology embed a consistent emotional pattern, allowing discrimination from a control group. The pool of web pages related to spine or hip/knee pathology was automatically selected by relevance and popularity and submitted to automated sentiment analysis to generate emotional patterns. Machine Learning (ML) algorithms were trained to predict page original topics from patterns with binary classification. ML showed high discrimination accuracy; disgust emerged as a discriminating emotion. The findings suggest that the digital affective "successful content" (collective consciousness) integrates patients' biopsychosocial ecosystem, with potential implications for the emergence of chronic pain, and the endorsement of health-relevant specific behaviors. Awareness of such effects raises practical and ethical issues for health information providers.

Clinical and forensic medicine issues in osteoporosis fractures.

Severe osteoporosis is characterized by a densitometry T-score lower than 2.5 associated with one or more fragility fractures. Fragility fractures represent a serious social and economic problem; the diagnosis of osteoporosis is an unachieved target by orthopaedic surgeons, despite the chance to detect it in many clinical assets and the availability of effective treatment tools. It is necessary to stick to scientific society guidelines, thus avoiding legal consequences related to the diagnosis, the therapy, the prescription coherence and the correct information due to patients.

Medium term follow up of the Biodynamic neck sparing prosthesis.

Hip resurfacing (HR) and neck sparing prostheses (NSP) have been advocated for the treatment of arthritis in younger patients. Some complications following HR have been documented in the recent literature, but NSP are not yet supported by clinical follow-up studies of sufficient duration. We present an assessment of the neck sparing "Biodynamic" prosthesis. 153 patients were evaluated in a longitudinal cohort prospective study, with survival analysis, clinical score and radiographic assessment of stability and osteointegration at 41.8 months average follow up. Survival and clinical outcome were similar to most traditional prostheses in the literature. On radiographic analysis we recorded good neck preservation and osteointegration. Only two stem failures were recorded. Poor clinical outcome was related to misalignment of prostheses implanted during the 'learning curve'. The NSP system described may be a good alternative to HR for younger patients. The system is characterized by good survival and clinical and radiographic outcome combined with bone stock preservation.

Osteoclastogenesis in peripheral blood mononuclear cell cultures of periprosthetic osteolysis patients and the phenotype of T cells localized in periprosthetic tissues.

Arthroplasty is a very successful medical procedure. Failures depend on aseptic loosening caused by periprosthetic osteolysis, where T cells have a contradictory role. We analyzed osteoclastogenesis in peripheral blood mononuclear cell (PBMC) cultures of periprosthetic osteolysis patients and the phenotype of T cells localized in periprosthetic tissues. We enrolled 45 subjects with periprosthetic osteolysis (15), stable prosthesis (15) and healthy controls (15). We performed PBMC cultures to study osteoclastogenesis. Osteoclasts and T cell phenotype were examined by immunohistochemistry, immunofluorescence and flow citometry. Periprosthetic osteolysis patients showed spontaneous osteoclastogenesis, which was inhibited by RANK-Fc and T cell depletion. In periprosthetic osteolysis patients' PBMC cultures, CD4 and CD8 T cells increased and CD8 T cells did not express CD25. In periprosthetic tissues T cells were close to osteoclasts, suggesting their interaction. Local CD8 T cells showed a regulatory phenotype, expressing CD25 and FoxP3, while CD4 T cells did not express activation markers. Our data suggest that, in an early stage of periprosthetic osteolysis, T cells may promote osteoclastogenesis, whereas subsequently osteoclasts activate FoxP3/CD8 T cells, which inhibit CD4 effector T cells. This mechanism may explain the previous finding of non-active T cells in periprosthetic tissues.

Bone invading NSCLC cells produce IL-7: mice model and human histologic data.

BACKGROUND: Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. METHODS: We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. RESULTS: At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. CONCLUSIONS: We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

Computer navigation versus conventional implantation for varus knee total arthroplasty: a case-control study at 5 years follow-up.

BACKGROUND: There is no evidence in the current literature of any significant improvement in clinical outcome when comparing computer-assisted total knee arthroplasty (CATKA) with conventional implantation. Analyses of alignment and of component orientation have shown both significant and non-significant differences between the two methods. OBJECTIVES: We compared computer-assisted and conventional surgery for TKA at 5.4 years follow-up for patients with varus osteoarthritic knees. Our goal was to assess clinical outcome and restoration of normal limb alignment. MATERIALS AND METHODS: We performed a retrospective case-control study comparing 30 patients who underwent CATKA with 30 subjects who underwent TKA by conventional methods. Patients were matched individually by preoperative clinical conditions and alignment. We analysed intraoperative data (surgical time and intraoperative complications), postoperative complications, lower limb alignment, radiographic complication on X-ray imaging, and clinical outcome through knee and function score and range of motion. RESULTS AND DISCUSSION: We found no significant clinical difference between the two groups at 5 years post-surgery. However there was a statistically significant improvement in the restoration of the mechanical axis of the lower limb in the coronal plane but not in the sagittal plane. Whether or not this leads to a higher survival rate in the longer term requires further investigation.