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Current Osteoporosis Reports Dec 2023The integration of data from multiple genomic assays from humans and non-human model organisms is an effective approach to identify genes involved in skeletal fragility... (Review)
Review
PURPOSE OF REVIEW
The integration of data from multiple genomic assays from humans and non-human model organisms is an effective approach to identify genes involved in skeletal fragility and fracture risk due to osteoporosis and other conditions. This review summarizes genome-wide genetic variation and gene expression data resources relevant to the discovery of genes contributing to skeletal fragility and fracture risk.
RECENT FINDINGS
Genome-wide association studies (GWAS) of osteoporosis-related traits are summarized, in addition to gene expression in bone tissues in humans and non-human organisms, with a focus on rodent models related to skeletal fragility and fracture risk. Gene discovery approaches using these genomic data resources are described. We also describe the Musculoskeletal Knowledge Portal (MSKKP) that integrates much of the available genomic data relevant to fracture risk. The available genomic resources provide a wealth of knowledge and can be analyzed to identify genes related to fracture risk. Genomic resources that would fill particular scientific gaps are discussed.
Topics: Humans; Bone Density; Genome-Wide Association Study; Genetic Predisposition to Disease; Osteoporosis; Fractures, Bone; Bone and Bones; Gene Expression; Biology
PubMed: 37831357
DOI: 10.1007/s11914-023-00821-7 -
Frontiers in Endocrinology 2023Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the aged population. Recent researches indicate that patients with AD... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is a neurodegenerative disorder that is the major cause of dementia in the aged population. Recent researches indicate that patients with AD have a significantly increased fracture risk, but the pathological mechanisms are still unclear.
OBJECTIVE
We systematically reviewed studies regarding bone fracture risk in AD to uncover links between the pathologies of osteoporosis and AD.
METHODS
We searched the literature using the databases of PubMed, Web of Science, Embase and Cochrane Library. Studies were included if they evaluated bone fracture risk in AD patients and if they explored the pathogenesis and prevention of bone fractures in these patients.
RESULTS
AD patients had a significantly higher risk of bone fractures than age-matched controls. Multiple factors contributed to the increased risk of bone fractures in AD patients, including the direct effects of amyloid pathology on bone cells, abnormal brain-bone interconnection, Wnt/β-catenin signalling deficits, reduced activity, high risk of falls and frailty, and chronic immune activity. Exercise, prevention of falls and fortified nutrition were beneficial for reducing the fracture risk in AD patients. However, the efficacy of anti-osteoporotic agents in preventing bone fractures should be further evaluated in AD patients as corresponding clinical studies are very scarce.
CONCLUSION
Alzheimer's disease patients have increased bone fracture risk and decreased bone mineral density owing to multiple factors. Assessment of anti-osteoporotic agents' efficacy in preventing bone fractures of AD patients is urgently needed.
Topics: Humans; Aged; Alzheimer Disease; Fractures, Bone; Osteoporosis; Amyloidogenic Proteins; Brain
PubMed: 37635980
DOI: 10.3389/fendo.2023.1190762 -
Ugeskrift For Laeger Oct 2023Management of circulatory unstable pelvic fracture in Greenland - from a remote village to Level 1 Trauma center. This case report depicts the transportation of an...
Management of circulatory unstable pelvic fracture in Greenland - from a remote village to Level 1 Trauma center. This case report depicts the transportation of an unstable patient in a rural area, where transportation of the critically ill patient is inherently difficult due to infrastructure. The case report brings knowledge to the reader of logistic conditions in Greenland, which differ greatly from those in Denmark. Furthermore, it highlights the importance of knowledge of damage control surgery and of great intercollegiate cooperation.
Topics: Humans; Cardiovascular System; Critical Illness; Fractures, Bone; Greenland; Pelvis; Male; Adult
PubMed: 37921100
DOI: No ID Found -
Revista Da Associacao Medica Brasileira... 2023
Topics: Female; Humans; Postmenopause; Fractures, Bone; Osteoporosis; Osteoporosis, Postmenopausal; Bone Density; Risk Factors; Osteoporotic Fractures; Risk Assessment
PubMed: 37556649
DOI: 10.1590/1806-9282.2023S130 -
Archives of Orthopaedic and Trauma... Sep 2023There is no widely accepted standard for the classification and treatment of traumatic acromion/scapular spine fracture nonunion due to the scarcity of this condition... (Review)
Review
INTRODUCTION
There is no widely accepted standard for the classification and treatment of traumatic acromion/scapular spine fracture nonunion due to the scarcity of this condition and the confusion of terminology.
MATERIALS AND METHODS
PubMed and Scopus were searched using "scapular fracture" and "acromion fracture" or "scapular spine fracture" as search terms. The inclusion criteria were English full-text articles concerning acromion/scapular spine fracture nonunion that described patient characteristics and presented appropriate images. The exclusion criteria were cases without appropriate images. Citation tracking was conducted to find additional articles and notable full-text articles written in other languages. Fractures were classified using our newly proposed classification system.
RESULTS
Twenty-nine patients (19 men, 10 women) with 29 nonunions were identified. There were four type I, 15 type II, and 10 type III fracture nonunions. Only 11 fractures were isolated. The mean period from initial injury to final diagnosis was 35.2 ± 73.2 months (range 3-360 months) (n = 25). The most frequent cause of delayed diagnosis was conservative treatment for fracture in 11 patients, followed by oversight by the physician in 8. The most common reason for seeking medical advice was shoulder pain. Six patients received conservative therapy, and 23 received operative treatment. Fixation materials included various plates in 15 patients, and tension band wiring in 5. Bone grafting was performed in 16 patients (73%, 16/22). Of the 19 surgically treated patients with adequate follow-up, the outcome was rated excellent in 79%.
CONCLUSIONS
Isolated acromion/scapular spine fracture nonunion is rare. Fracture type II and III, arising in the anatomical scapular spine, accounted for 86% of the fractures. Computed tomography is required to prevent fracture oversight. Surgical therapy produces good stable results. However, it is important to select the appropriate surgical fixation method and material after considering the anatomical characteristics of the fracture and stress on the fractured portion.
LEVEL OF EVIDENCE
V.
Topics: Male; Humans; Female; Acromion; Spinal Fractures; Fractures, Bone; Scapula; Fracture Fixation, Internal; Fractures, Ununited; Shoulder Fractures; Treatment Outcome
PubMed: 37314525
DOI: 10.1007/s00402-023-04912-z -
Nature Genetics Nov 2023Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are...
Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4 mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.
Topics: Animals; Mice; Forearm; Genome-Wide Association Study; Fractures, Bone; Bone Density; Risk Factors
PubMed: 37919453
DOI: 10.1038/s41588-023-01527-3 -
Journal of Orthopaedic Surgery and... Dec 2023Osteoporotic fractures impose a substantial burden on patients with diabetes due to their unique characteristics in bone metabolism, limiting the efficacy of... (Review)
Review
Osteoporotic fractures impose a substantial burden on patients with diabetes due to their unique characteristics in bone metabolism, limiting the efficacy of conventional fracture prediction tools. Artificial intelligence (AI) algorithms have shown great promise in predicting osteoporotic fractures. This review aims to evaluate the application of traditional fracture prediction tools (FRAX, QFracture, and Garvan FRC) in patients with diabetes and osteoporosis, review AI-based fracture prediction achievements, and assess the potential efficiency of AI algorithms in this population. This comprehensive literature search was conducted in Pubmed and Web of Science. We found that conventional prediction tools exhibit limited accuracy in predicting fractures in patients with diabetes and osteoporosis due to their distinct bone metabolism characteristics. Conversely, AI algorithms show remarkable potential in enhancing predictive precision and improving patient outcomes. However, the utilization of AI algorithms for predicting osteoporotic fractures in diabetic patients is still in its nascent phase, further research is required to validate their efficacy and assess the potential advantages of their application in clinical practice.
Topics: Humans; Osteoporotic Fractures; Artificial Intelligence; Bone Density; Risk Factors; Risk Assessment; Osteoporosis; Algorithms; Diabetes Mellitus; Hip Fractures
PubMed: 38087332
DOI: 10.1186/s13018-023-04446-5 -
Journal of Bone and Mineral Research :... Nov 2023Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early...
Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Mice; Animals; Cannabidiol; Cannabinoids; Bony Callus; Pain; Anti-Inflammatory Agents, Non-Steroidal; Tibial Fractures; Minerals; Fracture Healing
PubMed: 37597163
DOI: 10.1002/jbmr.4902 -
Deutsches Arzteblatt International Jan 2024Fracture-related infection (FRI) is a challenge to physicians and other workers in health care. In 2018, there were 7253 listed cases of FRI in Germany, corresponding to... (Review)
Review
BACKGROUND
Fracture-related infection (FRI) is a challenge to physicians and other workers in health care. In 2018, there were 7253 listed cases of FRI in Germany, corresponding to an incidence of 10.7 cases per 100 000 persons per year.
METHODS
This review is based on pertinent publications retrieved from a search in PubMed with the search terms "fracture," "infection," "guideline," and "consensus." Aside from the primary literature, international guidelines and consensus recommendations were evaluated as well.
RESULTS
FRI arise mainly from bacterial contamination of the fracture site. Staphylococcus aureus is the most commonly detected pathogen. The treatment is based on surgery and antibiotics and should be agreed upon by an interdisciplinary team; it is often difficult because of biofilm formation. Treatment options include implant-preserving procedures and single-stage, two-stage, or multi-stage implant replacement. Treatment failure occurs in 10.3% to 21.4% of cases. The available evidence on the efficacy of various treatment approaches is derived mainly from retrospective cohort studies (level III evidence). Therefore, periprosthetic joint infections and FRI are often discussed together.
CONCLUSION
FRI presents an increasing challenge. Preventive measures should be optimized, and the treatment should always be decided upon by an interdisciplinary team. Only low-level evidence is available to date to guide diagnostic and treatment decisions. High-quality studies are therefore needed to help us meet this challenge more effectively.
Topics: Humans; Retrospective Studies; Fractures, Bone; Anti-Bacterial Agents; Causality; Staphylococcal Infections
PubMed: 37970721
DOI: 10.3238/arztebl.m2023.0233 -
Advanced Science (Weinheim,... Dec 2023Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute...
Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves treatment with NSAIDs and opioids with substantial adverse effects. Herein, we tested the hypothesis that the purine molecule, adenosine, can simultaneously alleviate pain and promote healing in a mouse model of tibial fracture by targeting distinctive adenosine receptor subtypes in different cell populations. To achieve this, a biomaterial-assisted delivery of adenosine is utilized to localize and prolong its therapeutic effect at the injury site. The results demonstrate that local delivery of adenosine inhibited the nociceptive activity of peripheral neurons through activation of adenosine A1 receptor (ADORA1) and mitigated pain as demonstrated by weight bearing and open field movement tests. Concurrently, local delivery of adenosine at the fracture site promoted osteogenic differentiation of mesenchymal stromal cells through adenosine A2B receptor (ADORA2B) resulting in improved bone healing as shown by histological analyses and microCT imaging. This study demonstrates the dual role of adenosine and its material-assisted local delivery as a feasible therapeutic approach to treat bone trauma and associated pain.
Topics: Animals; Mice; Osteogenesis; Fracture Healing; Fractures, Bone; Pain; Adenosine
PubMed: 37939302
DOI: 10.1002/advs.202303567