-
Current Osteoporosis Reports Oct 2020Fractures are painful and disabling injuries that can occur due to trauma, especially when compounded with pathologic conditions, such as osteoporosis in older adults.... (Review)
Review
PURPOSE OF REVIEW
Fractures are painful and disabling injuries that can occur due to trauma, especially when compounded with pathologic conditions, such as osteoporosis in older adults. It is well documented that acute pain management plays an integral role in the treatment of orthopedic patients. There is no current therapy available to completely control post-fracture pain that does not interfere with bone healing or have major adverse effects. In this review, we focus on recent advances in the understanding of pain behaviors post-fracture.
RECENT FINDINGS
We review animal models of bone fracture and the assays that have been developed to assess and quantify spontaneous and evoked pain behaviors, including the two most commonly used assays: dynamic weight bearing and von Frey testing to assess withdrawal from a cutaneous (hindpaw) stimulus. Additionally, we discuss the assessment and quantification of fracture pain in the clinical setting, including the use of numeric pain rating scales, satisfaction with pain relief, and other biopsychosocial factor measurements. We review how pain behaviors in animal models and clinical cases can change with the use of current pain management therapies. We conclude by discussing the use of pain behavioral analyses in assessing potential therapeutic treatment options for addressing acute and chronic fracture pain without compromising fracture healing. There currently is a lack of effective treatment options for fracture pain that reliably relieve pain without potentially interfering with bone healing. Continued development and verification of reliable measurements of fracture pain in both pre-clinical and clinical settings is an essential aspect of continued research into novel analgesic treatments for fracture pain.
Topics: Acute Pain; Animals; Behavior, Animal; Chronic Pain; Disease Models, Animal; Fracture Healing; Fractures, Bone; Humans; Pain; Pain Management; Pain Measurement; Weight-Bearing
PubMed: 32827293
DOI: 10.1007/s11914-020-00617-z -
Current Osteoporosis Reports Jun 2021Bone matrix exhibits great complexity in its composition, structure and mechanics. Here, we provide a review of recent research articles and appraise the evidence that... (Review)
Review
PURPOSE OF REVIEW
Bone matrix exhibits great complexity in its composition, structure and mechanics. Here, we provide a review of recent research articles and appraise the evidence that bone matrix quality is clinically important and possibly targetable for fracture prevention.
RECENT FINDINGS
Deformation of mineralised collagen fibrils determines bone fracture mechanics. Slipping and separation at the mineral-fibril and fibril-fibril interfaces, respectively, are the structural mechanisms for plastic deformation and microcrack nucleation. Existing technologies for assessing bone tissue in vivo cannot measure matrix structure or fracture mechanics but have shown limited use in clinical settings for identifying fragility or following treatment outcomes based on composition. Matrix is biomechanically and clinically important, but the knowledge has not translated into clinical practice. The structural mechanisms by which a load is transferred from mineralised collagen fibrils to the whole bone via microcracking have been proven too complex to measure in vivo. The mineral-fibril or fibril-fibril interfaces might be suitable targets for diagnosing fragility or delivering molecules that reduce fracture risk by strengthening the mineral bonds while maintaining flexibility in the fibrils.
Topics: Biomechanical Phenomena; Bone Matrix; Collagen; Elastic Modulus; Fractures, Bone; Humans; Stress, Mechanical
PubMed: 33876386
DOI: 10.1007/s11914-021-00678-8 -
European Cells & Materials Oct 2020An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic... (Review)
Review
An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic burden for society. Osteoporotic fractures are frequently located in metaphyseal bone regions. They are often associated with healing complications, because of the reduced healing capacity of the diseased bone tissue, the poor primary stability of the fracture fixation in the fragile bone, and the high frequency of comorbidities in these patients. Therefore, osteoporotic fractures require optimised treatment strategies to ensure proper bone healing. Preclinical animal models can help understanding of the underlying mechanisms and development of new therapies. However, whereas diaphyseal fracture models are widely available, appropriate animal models for metaphyseal fracture healing are scarce, although essential for translational research. This review covers large and small animal models for metaphyseal fracture healing. General requirements for suitable animal models are presented, as well as advantages and disadvantages of the current models. Furthermore, differences and similarities between metaphyseal and diaphyseal bone fracture healing are discussed. Both large- and small-animal models are available for studying metaphyseal fracture healing, which mainly differ in fracture location and geometry as well as stabilisation techniques. Most common used fracture sites are distal femur and proximal tibia. Each model found in the literature has certain advantages and disadvantages; however, many lack standardisation resulting in a high variability or poor mimicking of the clinical situation. Therefore, further refinement ofanimal models is needed especially to study osteoporotic metaphyseal fracture healing.
Topics: Animals; Diaphyses; Disease Models, Animal; Fracture Healing; Fractures, Bone
PubMed: 33119886
DOI: 10.22203/eCM.v040a11 -
BMJ Open Diabetes Research & Care Apr 2021Type 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in...
INTRODUCTION
Type 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D.
RESEARCH DESIGN AND METHODS
The single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery.
RESULTS
A total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (p<0.001 vs no fracture).
CONCLUSIONS
We have shown that a history of severe hypoglycemia is significantly associated with a higher risk of bone fracture in Japanese patients with T1D.
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Fractures, Bone; Humans; Hypoglycemia; Japan; Middle Aged; Prevalence
PubMed: 33888545
DOI: 10.1136/bmjdrc-2020-002099 -
International Journal of Molecular... Nov 2019Mesenchymal stem cells (MSCs) are capable of differentiating into multilineage cells, thus making them a significant prospect as a cell source for regenerative therapy;... (Review)
Review
Mesenchymal stem cells (MSCs) are capable of differentiating into multilineage cells, thus making them a significant prospect as a cell source for regenerative therapy; however, the differentiation capacity of MSCs into osteoblasts seems to not be the main mechanism responsible for the benefits associated with human mesenchymal stem cells hMSCs when used in cell therapy approaches. The process of bone fracture restoration starts with an instant inflammatory reaction, as the innate immune system responds with cytokines that enhance and activate many cell types, including MSCs, at the site of the injury. In this review, we address the influence of MSCs on the immune system in fracture repair and osteogenesis. This paradigm offers a means of distinguishing target bone diseases to be treated with MSC therapy to enhance bone repair by targeting the crosstalk between MSCs and the immune system.
Topics: Animals; Cell Differentiation; Cytokines; Fractures, Bone; Humans; Immunomodulation; Mesenchymal Stem Cells; Osteoblasts; Osteogenesis; Regenerative Medicine
PubMed: 31684035
DOI: 10.3390/ijms20215467 -
Molecular Therapy : the Journal of the... Feb 2023Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for...
Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/β-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.
Topics: Humans; Adaptor Proteins, Signal Transducing; Osteoporosis; Fractures, Bone; Bone and Bones; Genetic Therapy
PubMed: 36184851
DOI: 10.1016/j.ymthe.2022.09.018 -
Current Osteoporosis Reports Oct 2020Compared with the current standard of implanting bone anabolics for fracture repair, bone fracture-targeted anabolics would be more effective, less invasive, and less... (Review)
Review
PURPOSE OF REVIEW
Compared with the current standard of implanting bone anabolics for fracture repair, bone fracture-targeted anabolics would be more effective, less invasive, and less toxic and would allow for control over what phase of fracture healing is being affected. We therefore sought to identify the optimal bone-targeting molecule to allow for systemic administration of therapeutics to bone fractures.
RECENT FINDINGS
We found that many bone-targeting molecules exist, but most have been developed for the treatment of bone cancers, osteomyelitis, or osteoporosis. There are a few examples of bone-targeting ligands that have been developed for bone fractures that are selective for the bone fracture over the body and skeleton. Acidic oligopeptides have the ideal half-life, toxicity profile, and selectivity for a bone fracture-targeting ligand and are the most developed and promising of these bone fracture-targeting ligands. However, many other promising ligands have been developed that could be used for bone fractures.
Topics: Alkaline Phosphatase; Amino Acids, Acidic; Anabolic Agents; Diphosphonates; Drug Delivery Systems; Durapatite; Fracture Healing; Fractures, Bone; Humans; Immunoglobulin G; Oligopeptides; Recombinant Fusion Proteins; Tartrate-Resistant Acid Phosphatase; Tetracycline
PubMed: 32860563
DOI: 10.1007/s11914-020-00604-4 -
Sensors (Basel, Switzerland) Aug 2019Since the advantages of precise operation and effective reduction of radiation, robots have become one of the best choices for solving the defects of traditional... (Review)
Review
Since the advantages of precise operation and effective reduction of radiation, robots have become one of the best choices for solving the defects of traditional fracture reduction surgery. This paper focuses on the application of robots in fracture reduction surgery, design of the mechanism, navigation technology, robotic control, interaction technology, and the bone-robot connection technology. Through literature review, the problems in current fracture reduction robot and its future development are discussed.
Topics: Fracture Fixation; Fractures, Bone; Humans; Robotics; Surgery, Computer-Assisted
PubMed: 31426577
DOI: 10.3390/s19163593 -
Sensors (Basel, Switzerland) Aug 2022An expert performs bone fracture diagnosis using an X-ray image manually, which is a time-consuming process. The development of machine learning (ML), as well as deep...
An expert performs bone fracture diagnosis using an X-ray image manually, which is a time-consuming process. The development of machine learning (ML), as well as deep learning (DL), has set a new path in medical image diagnosis. In this study, we proposed a novel multi-scale feature fusion of a convolution neural network (CNN) and an improved canny edge algorithm that segregate fracture and healthy bone image. The hybrid scale fracture network (SFNet) is a novel two-scale sequential DL model. This model is highly efficient for bone fracture diagnosis and takes less computation time compared to other state-of-the-art deep CNN models. The innovation behind this research is that it works with an improved canny edge algorithm to obtain edges in the images that localize the fracture region. After that, grey images and their corresponding canny edge images are fed to the proposed hybrid SFNet for training and evaluation. Furthermore, the performance is also compared with the state-of-the-art deep CNN models on a bone image dataset. Our results showed that SFNet with canny (SFNet + canny) achieved the highest accuracy, F1-score and recall of 99.12%, 99% and 100%, respectively, for bone fracture diagnosis. It showed that using a canny edge algorithm improves the performance of CNN.
Topics: Algorithms; Deep Learning; Fractures, Bone; Humans; Machine Learning; Neural Networks, Computer
PubMed: 35957380
DOI: 10.3390/s22155823 -
Proceedings of the National Academy of... Jul 2021Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have...
Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Here, we present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. We demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.
Topics: Absorbable Implants; Animals; Biofeedback, Psychology; Electric Power Supplies; Electric Stimulation Therapy; Electricity; Equipment Design; Fracture Healing; Fractures, Bone; Rats; Reference Standards
PubMed: 34260393
DOI: 10.1073/pnas.2100772118