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Age and Ageing Apr 2022Fragility fractures are painful, debilitating, often life-changing and accounted for an estimated 2.4% of pre-pandemic health care spending in the UK. Those who are...
Fragility fractures are painful, debilitating, often life-changing and accounted for an estimated 2.4% of pre-pandemic health care spending in the UK. Those who are older, frail and multimorbid have the highest fracture risk and therefore the most to gain from anti-osteoporosis treatments to reduce this risk. Currently, an unacceptable treatment gap exists between those eligible for and those who receive treatment. This commentary discusses the major changes to the new, National Institute for Health and Care Excellence accredited, UK National Osteoporosis Guideline Group (NOGG) guidance (published March 2022) most relevant to the management of older people's bone health. Changes include intervention thresholds; using fracture probabilities from FRAX; for patients too frail to undergo DXA; greater emphasis on vertebral fracture detection and the use of intravenous zoledronate as a first-line anti-osteoporosis therapy; the new concept of 'very high fracture risk' which should prompt consideration of use of parenteral anti-osteoporosis therapy; new guidance regarding anabolic treatment options; concerns regarding denosumab cessation; and the urgent need to get patients with a fragility fracture onto treatment to reduce re-fracture risk with follow-up to check tolerance and ensure adherence.
Topics: Aged; Bone Density; Geriatricians; Humans; Osteoporosis; Osteoporotic Fractures; Risk Assessment; Risk Factors
PubMed: 35403198
DOI: 10.1093/ageing/afac044 -
Current Opinion in Neurology Oct 2018Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk... (Review)
Review
PURPOSE OF REVIEW
Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk of osteoporosis. Osteoporotic fracture is an important and preventable cause of morbidity and mortality. This article will firstly review the general causes of impaired bone health in muscular dystrophies and then focus on the evidence available for the diagnosis and treatment of osteoporosis in specific conditions.
RECENT FINDINGS
With the exception of DMD, there is a paucity of data regarding bone health in muscular dystrophies. However, it appears that in common with all types of muscular dystrophies that cause a significant level of muscle weakness and disability there is an increased risk of falls, fractures and decreased vitamin D levels. A better understanding of the extent of the impaired bone health and underlying causes could help to identify potential new therapeutic agents and aid clinical care.
SUMMARY
It would be prudent for clinicians to assess fracture risk in their muscular dystrophy patients and if appropriate, arrange surveillance and recommend vitamin D supplementation. Additionally, fracture should be considered in any patient presenting with new-onset bone pain.
Topics: Bone Diseases; Bone and Bones; Humans; Muscular Dystrophies; Osteoporotic Fractures; Risk Assessment
PubMed: 30080716
DOI: 10.1097/WCO.0000000000000603 -
Current Opinion in Rheumatology Jul 2019Artificial intelligence tools have found new applications in medical diagnosis. These tools have the potential to capture underlying trends and patterns, otherwise... (Review)
Review
PURPOSE OF REVIEW
Artificial intelligence tools have found new applications in medical diagnosis. These tools have the potential to capture underlying trends and patterns, otherwise impossible with previous modeling capabilities. Machine learning and deep learning models have found a role in osteoporosis, both to model the risk of fragility fracture, and to help with the identification and segmentation of images.
RECENT FINDINGS
Here we survey the latest research in the artificial intelligence application to the prediction of osteoporosis that has been published between January 2017 and March 2019. Around half of the articles that are covered here predict (by classification or regression) an indicator of osteoporosis, such as bone mass or fragility fractures; the other half of studies use tools for automatic segmentation of the images of patients with or at risk of osteoporosis. The data for these studies include diverse signal sources: acoustics, MRI, CT, and of course, X-rays.
SUMMARY
New methods for automatic image segmentation, and prediction of fracture risk show promising clinical value. Though these recent developments have had a successful initial application to osteoporosis research, their development is still under improvement, such as accounting for positive/negative class bias. We urge care when reporting accuracy metrics, and when comparing such metrics between different studies.
Topics: Artificial Intelligence; Bone Density; Frailty; Humans; Magnetic Resonance Imaging; Osteoporotic Fractures; Tomography, X-Ray Computed
PubMed: 31045948
DOI: 10.1097/BOR.0000000000000607 -
Journal of Bone and Mineral Research :... Sep 2023Osteoporotic vertebral fracture (OVF) is a risk factor for morbidity and mortality in elderly population, and accurate diagnosis is important for improving treatment...
Osteoporotic vertebral fracture (OVF) is a risk factor for morbidity and mortality in elderly population, and accurate diagnosis is important for improving treatment outcomes. OVF diagnosis suffers from high misdiagnosis and underdiagnosis rates, as well as high workload. Deep learning methods applied to plain radiographs, a simple, fast, and inexpensive examination, might solve this problem. We developed and validated a deep-learning-based vertebral fracture diagnostic system using area loss ratio, which assisted a multitasking network to perform skeletal position detection and segmentation and identify and grade vertebral fractures. As the training set and internal validation set, we used 11,397 plain radiographs from six community centers in Shanghai. For the external validation set, 1276 participants were recruited from the outpatient clinic of the Shanghai Sixth People's Hospital (1276 plain radiographs). Radiologists performed all X-ray images and used the Genant semiquantitative tool for fracture diagnosis and grading as the ground truth data. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to evaluate diagnostic performance. The AI_OVF_SH system demonstrated high accuracy and computational speed in skeletal position detection and segmentation. In the internal validation set, the accuracy, sensitivity, and specificity with the AI_OVF_SH model were 97.41%, 84.08%, and 97.25%, respectively, for all fractures. The sensitivity and specificity for moderate fractures were 88.55% and 99.74%, respectively, and for severe fractures, they were 92.30% and 99.92%. In the external validation set, the accuracy, sensitivity, and specificity for all fractures were 96.85%, 83.35%, and 94.70%, respectively. For moderate fractures, the sensitivity and specificity were 85.61% and 99.85%, respectively, and 93.46% and 99.92% for severe fractures. Therefore, the AI_OVF_SH system is an efficient tool to assist radiologists and clinicians to improve the diagnosing of vertebral fractures. © 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: Aged; Humans; Spinal Fractures; Artificial Intelligence; China; Osteoporotic Fractures; Spine
PubMed: 37449775
DOI: 10.1002/jbmr.4879 -
Bone Mar 2016Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon... (Review)
Review
INTRODUCTION
Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture.
METHODS/RESULTS
Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed.
CONCLUSIONS
Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups.
MINI ABSTRACT
Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Humans; Models, Biological; Osteoporotic Fractures; Socioeconomic Factors
PubMed: 26723576
DOI: 10.1016/j.bone.2015.12.015 -
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 -
Osteoporosis International : a Journal... Jan 2022We estimated and characterized the imminent fracture risk (1-2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older... (Observational Study)
Observational Study
UNLABELLED
We estimated and characterized the imminent fracture risk (1-2 years) of high-risk fracture patients through a multinational (UK, Spain, Denmark) cohort study. Older individuals with newly diagnosed osteoporosis and individuals who had a fracture while on treatment with a bisphosphonate were at a high risk of imminent fracture.
PURPOSE
To characterize and estimate 1- to 2-year fracture risk in high-risk fracture patients.
METHODS
Multi-cohort study in (database/study period) UK (CPRD/1995-2017), Spain (SIDIAP/2006-2016) and Denmark (DHR/1995-2016) including individuals ≥ 50 years old in NDO (newly diagnosed osteoporosis), OFx (incident osteoporotic fracture), BP (incident oral bisphosphonates use) or FWOT (fracture while on treatment with bisphosphonates). Outcomes (ICD-10/READ): hip, clinical spine, non-hip, non-spine and hip/humerus/distal forearm fracture.
FOLLOW-UP
from cohort entry until death, migration/transfer or end of the study.
STATISTICS
baseline characteristics and incidence rate (IR per 1000 persons). RESULTS (1-YEAR IR): NDO included 69,899 (UK), 37,901 (Spain) and 158,191 (Denmark) individuals. Spanish-IR was lowest for hip (4.7), clinical spine (2.5) and major osteoporotic fracture (MOF) (17.3) and highest in Denmark (74.2, 26.0 and 120.1, respectively). OFx included 83,514 (UK), 51,044 (Spain) and 509,551 (Denmark) individuals. IR in Denmark was highest for hip (24.1) and MOF (47.2), in Spain was highest for the clinical spine (9.4) and lowest for hip (9.5) and in the UK was lowest for the clinical spine (2.8) and MOF (20.7). BP included 148,507 (UK), 52,037 (Spain) and 204,010 (Denmark) individuals. Spanish-IR was lowest for hip (5.0) and MOF (21.1) and highest in Denmark (20.3 and 48.6, respectively). FWOT included 28,930 (UK), 1,865 (Spain) and 31,882 (Denmark) individuals. Clinical spine-IR was highest for Spain (12.0). Hip-IR was lowest for Spain (7.6) and highest for Denmark (33.6). Comparing young subjects, those who have FWOT started with an increased fracture rate.
CONCLUSION
OFx and FWOT individuals experience higher re-fracture incidence rates than those with osteoporosis with or without treatment.
Topics: Cohort Studies; Hip Fractures; Humans; Incidence; Middle Aged; Osteoporosis; Osteoporotic Fractures; Risk Factors
PubMed: 34392386
DOI: 10.1007/s00198-021-06077-0 -
Nutrients May 2022Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as...
Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.
Topics: Animals; Chondrogenesis; Dioxoles; Female; Fracture Healing; Humans; Lignans; Mice; Osteoporotic Fractures; Rats; Rats, Sprague-Dawley
PubMed: 35631249
DOI: 10.3390/nu14102106 -
ELife Mar 2021More informed discussions between physicians and older adults about the consequences of an initial osteoporotic fracture could encourage more patients to consider...
More informed discussions between physicians and older adults about the consequences of an initial osteoporotic fracture could encourage more patients to consider treatments that protect against future fracture.
Topics: Aged; Bone Density; Humans; Osteoporosis; Osteoporotic Fractures
PubMed: 33650970
DOI: 10.7554/eLife.66916 -
Frontiers in Endocrinology 2021The clinical need for effective osteoporotic fracture therapy and prevention remains urgent. The occurrence and healing of osteoporotic fracture are closely associated... (Review)
Review
The clinical need for effective osteoporotic fracture therapy and prevention remains urgent. The occurrence and healing of osteoporotic fracture are closely associated with the continuous processes of bone modeling, remodeling, and regeneration. Accumulating evidence has indicated a prominent role of exosomes in mediating multiple pathophysiological processes, which are essential for information and materials exchange and exerting pleiotropic effects on neighboring or distant bone-related cells. Therefore, the exosomes are considered as important candidates both in the occurrence and healing of osteoporotic fracture by accelerating or suppressing related processes. In this review, we collectively focused on recent findings on the diagnostic and therapeutic applications of exosomes in osteoporotic fracture by regulating osteoblastogenesis, osteoclastogenesis, and angiogenesis, providing us with novel therapeutic strategies for osteoporotic fracture in clinical practice.
Topics: Bone and Bones; Exosomes; Fracture Healing; Humans; Osteoporotic Fractures
PubMed: 34234743
DOI: 10.3389/fendo.2021.679914