Unraveling the molecular and immunological landscape: Exploring signaling pathways in osteoporosis.

Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This comprehensive review delves into the intricate signaling pathways implicated in the pathogenesis of osteoporosis, providing valuable insights into the pivotal role of signal transduction in maintaining bone homeostasis. The exploration encompasses cellular signaling pathways such as Wnt, Notch, JAK/STAT, NF-κB, and TGF-ß, all of which play crucial roles in bone remodeling. The dysregulation of these pathways is a contributing factor to osteoporosis, necessitating a profound understanding of their complexities to unveil the molecular mechanisms underlying bone loss. The review highlights the pathological significance of disrupted signaling in osteoporosis, emphasizing how these deviations impact the functionality of osteoblasts and osteoclasts, ultimately resulting in heightened bone resorption and compromised bone formation. A nuanced analysis of the intricate crosstalk between these pathways is provided to underscore their relevance in the pathophysiology of osteoporosis. Furthermore, the study addresses some of the most crucial long non-coding RNAs (lncRNAs) associated with osteoporosis, adding an additional layer of academic depth to the exploration of immune system involvement in various types of osteoporosis. Finally, we propose that SKP1 can serve as a potential biomarker in osteoporosis.

Prediction of subsequent fragility fractures: application of machine learning.

BACKGROUND: Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients. METHODS: We retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation. RESULTS: The CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score. CONCLUSION: ML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.

Epidemiological Characteristics of Pediatric Supracondylar of Humerus Fractures in a Tertiary Hospital in Iran.

Objectives: Supracondylar humerus fracture (SHF) is the most common fracture observed in children. The present study aimed to assess the characteristic parameters in one of the most extensive available pediatric SHF series referred to a tertiary hospital in Iran. Methods: The medical profiles of the SHF patients who were referred to our tertiary hospital between January 2017 and January 2022 were retrospectively reviewed. The inclusion criteria entailed age < 14 years and a radiographically confirmed diagnosis of SHF. The collected data included age, gender, side of injury, mechanism of injury, season of the injury, concurrent complications, type of fracture, and treatment. Results: A total of 1,309 patients with a mean age of 7.7±2.7 years were included in this study. The incidence of SHF was 1.8-fold higher in males, while the mean age of incidence was significantly lower in female patients (7.2 vs. 8 years; P<0.001). Falling was the most frequent mechanism of injury (97%). Gartland type I was the most prevalent type of injury (n=482; 36.8%). Moreover, the majority of fractures were extension-type (n=1,249; 95.4%). Most patients were managed conservatively (n=785; 60%). Concurrent fractures as well as neuralgic, vascular, and muscular complications were present in 3%, 1.45%, 1.22%, and 0.5% of patients, respectively. Conclusion: As evidenced by the results of this study, SHF is prevalent among the Iranian pediatric population. Therefore, greater awareness is required regarding the high incidence of this fracture in this population and its adequate management with respect to concurrent complications, particularly neurovascular compromise.

The process of hip fracture management before and during the COVID-19 pandemic in Iran.

BACKGROUND: The COVID-19 pandemic affected the control of many chronic conditions, including hip fractures, worldwide. This study was to examine the impact of the COVID-19 pandemic on the management of hip fractures in a referral orthopedic hospital in Iran. By understanding how the pandemic has influenced the care of hip fracture patients, we can gain valuable insights into the challenges, adaptations, and potential improvements in orthopedic healthcare during such public health crises. METHODS: Data was collected on hip fracture patients aged 50 and above who were admitted to the hospital before and during the pandemic. The number of admissions and operations, length of hospital stay, and time from admission to surgery were recorded from the hospital information system (HIS) and compared between the two periods. RESULTS: The median number of admitted hip fracture patients per month increased slightly during the pandemic (11%), although this increase was not statistically significant (p = 0.124). After adjusting for potential confounders, the mean length of hospital stay was significantly lower during the pandemic period, indicating that patients were discharged sooner (p = 0.019) and the time from admission to surgery was shorter during the pandemic (p = 0.004). Although the increase in the number of hip fracture surgeries per month during the pandemic was not statistically significant (P = 0.132), a higher percentage of patients underwent surgery during the pandemic compared to before (84.8% VS. 79.4%). CONCLUSION: The study suggests that the COVID-19 pandemic did not have a negative impact on hip fracture management in the investigated orthopedic hospital in Iran. further research is needed to explore the effects of the pandemic on other aspects of healthcare services, particularly in general hospitals.

Dry needling in a multimodal rehabilitation protocol following rotator cuff repair surgery: study protocol for a double-blinded randomized sham-controlled trial.

BACKGROUND: Rotator cuff tear (RCT) is one of the main causes of shoulder pain and dysfunction. Rotator cuff repair (RCR) is a common surgical procedure for the management of RCTs. Presence of myofascial trigger points (MTrP) as a result of surgical procedure can aggravate postoperative shoulder pain. The purpose of this protocol is to describe a randomized controlled trial design to evaluate the effect of implementing 4 sessions of myofascial trigger point dry needling (MTrP-DN) within a multimodal rehabilitation protocol following RCR surgery. METHODS: Forty-six participants aged 40-75 will be recruited having postoperative shoulder pain after RCR and meeting the inclusion criteria. Participants will be randomly divided into 2 groups: One group will undergo MTrP-DN, manual therapy, exercise therapy and electrotherapy and the other will receive sham dry needling (S-DN), manual therapy, exercise therapy and electrotherapy. This protocol will cover 4 weeks of intervention. The primary outcome measure will be the Numeric Pain Rating Scale (NPRS) for pain. Secondary outcome measures will be Shoulder Pain and Disability Index (SPDI), range of motion (ROM), strength and adverse events. DISCUSSION: This is the first study to investigate the use of 4 sessions of MTrP-DN in combination with a multimodal rehabilitation protocol for postoperative shoulder pain, restriction, weakness and dysfunction following RCR. The results of this study may help to determine the effect of MTrP-DN on various outcomes after RCR surgery. TRIAL REGISTRATION: This trial was registered at the ( https://www.irct.ir ), (IRCT20211005052677N1) on 19/2/2022.

COVID-19 among patients with orthopedic surgery: our experience from the Middle East.

BACKGROUND: We report our experiences with COVID-19 in one of the largest referral orthopedic centers in the Middle East and aimed to describe the epidemiology and clinical characteristics of these patients. METHODS: During February 20 and April 20, 2020, patients who underwent orthopedic surgery and healthcare staff who were in contact with these patients were screened for COVID-19. To identify patients who were in the incubation period of COVID-19 during their hospital stay, all patients were tested again for COVID-19 4 weeks after discharge. RESULTS: Overall, 1244 patients underwent orthopedic surgery (1123 emergency and 121 elective) during the study period. Overall, 17 patients were diagnosed with COVID-19 during hospital admission and seven after discharge. Among the total 24 patients with COVID-19, 15 were (62.5%) males with a mean (SD) age of 47.0±1.6 years old. Emergency surgeries were performed in 20 (83.3%) patients, and elective surgery was done in the remaining 4 patients which included one case of posterior spinal fusion, spondylolisthesis, acromioclavicular joint dislocation, and one case of leg necrosis. A considerable number of infections occurred in patients with intertrochanteric fractures (n=7, 29.2%), followed by pelvic fractures (n=2, 8.3%), humerus fractures (n=2, 8.3%), and tibial plateau fractures (n=2, 8.3%). Fever (n=11, 45.8%) and cough (n=10, 37.5%) were the most common symptoms among patients. Laboratory examinations showed leukopenia in 2 patients (8.3%) and lymphopenia in 4 (16.7%) patients. One patient with a history of cancer died 2 weeks after discharge due to myocardial infarction. Among hospital staff, 26 individuals contracted COVID-19 during the study period, which included 13 (50%) males. Physicians were the most commonly infected group (n = 11), followed by operation room technicians (n = 5), nurses (n = 4), and paramedics (n = 4). CONCLUSIONS: Patients who undergo surgical treatment for orthopedic problems, particularly lower limb fractures with limited ambulation, are at a higher risk of acquiring COVID-19 infections, although they may not be at higher risks for death compared to the general population. Orthopedic surgeons in particular and other hospital staff who are in close contact with these patients must be adequately trained and given appropriate personal protective equipment during the COVID-19 outbreak.

Influence of muscarinic receptor modulators on interacerebroventricular injection of arachydonylcyclopropylamide induced antinociception in mice.

The interaction between antinociception induced by CB1 agonist and muscarinic receptor modulators has not been studied yet. In the present study, the effect of pilocarpine (a muscarinic agonist) and atropine (a muscarinic antagonist) on arachidonylcyclopropylamide (ACPA, a CB1 agonist) induced antinociception was studied in mice. In this study the antinociceptive effect of intracerebroventricular administration of ACPA (0.001-2 µg/mice) or intraperitoneal injection of pilocarpine (2.5-20mg/kg) or atropine (1 and 5mg/kg) were studied individually. Then the effect of co-administration of pilocarine (2.5mg/kg) or atropine (5mg/kg) and ACPA (0.001-2 µg/mice) were studied as well. ACPA and pilocarpine induced antinociception in mice but atropine did not. Pilocarpine potentiated but atropine antagonized the antinociceptive effect of ACPA. It is concluded that ACPA induced antinociception is influenced by muscarinic receptor modulators in mice.

The preventive effect of cannabinoids on reperfusion-induced ischemia of mouse kidney.

Artery occlusion of an organ results in ischemia. When the occlusion is opened and blood flow reinstated there will be tissue injuries identified as reperfusion-induced ischemia (RII). It has been suggested that cannabinoids (CBs) may be involved in the RII. In this study, we assessed the effect of different doses of anandamide analogs and CB receptor agonists: arachidonylcyclopropylamide (ACPA, a CB1 agonist) and JWH133 (a CB2 agonist) in the RII of the mouse kidney. Three doses (0.2, 1 and 5mg/kg, i.p.) of ACPA or JWH133 were used 30min prior initiation of RII. Kidneys were removed 2 and 24h following RII and checked histologically for the grading of ischemic injury. Appropriate control groups were used as well. RII produced lesion comparable with that of ischemia. Different doses of ACPA or JWH133 prevented RII-induced lesions. It is suggestive of the CB system involvement in the kidney RII in mice.