Journal articles on the topic 'Fracture risk estimation'
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Adamopoulos, Panagiotis A., Abraham Pouliakis, Aris T. Spathis, Christine Kottaridi, and Petros Karakitsos. "Gene Polymorphisms and their Transcripts as Factors for Computerized Assessment of Fracture Risk." International Journal of Reliable and Quality E-Healthcare 4, no. 3 (July 2015): 27–46. http://dx.doi.org/10.4018/ijrqeh.2015070103.
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The aim of this study is the evaluation of osteoporosis related genes and transcription products, demographic and medication data for the estimation of fracture risk in women with osteoporosis. Such estimations are important for the creation of computerized applications similar to the Fracture Risk Assessment Tool (FRAX®). Low cost Internet based tools were used for the creation of anonymised patient record stored in the Cloud, and for an interdisciplinary team to decide on patient inclusion via voice and video conference. 100 female patients with an osteoporotic fracture, on medication or not were included in the study. A series of seven biochemical parameters using the Luminex® technique were measured and genetic characteristics using the microarray Metabone® technique were analysed. The statistical analysis indicated that these new parameters can be important for the estimation of fracture risk; thus computer based risk estimation for fractures could be based on additional molecular data.
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Papakonstantinopoulou, Konstantina, and Ioannis Sofianos. "The role of cystatin C in the risk of hip fractures in the elderly." Journal of Research and Practice on the Musculoskeletal System 4, no. 4 (December 1, 2020): 108–12. http://dx.doi.org/10.22540/jrpms-04-108.
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World’s population is aging. The elderly are at high risk for both chronic kidney disease (CKD) and hip fractures. Severe chronic kidney disease is a well-known risk factor for fractures and death especially in the elderly. Mild and moderate stages of kidney disease are often undiagnosed and/or untreated, thus their effect on fracture risk is not well established. Many ways of estimating glomerular filtration rate (GFR) have been developed but there are very few studies recommending the best and most valuable method for estimated GFR (eGFR) calculation that could correlate with fracture risk. In this mini- review we searched the literature concerning the use of cystatin C in the estimation of GFR related to the risk of hip fractures in the elderly. Our goal was to review the most important recent evidence on whether cystatin C could become a useful biomarker for the prediction of fracture risk. We concluded that there is evidence to support the use of cystatin C in hip fracture risk prediction in elder patients with chronic kidney disease.
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Mok, Chi Chiu, Sau Mei Tse, Kar Li Chan, and Ling Yin Ho. "Estimation of fracture risk by the FRAX tool in patients with systemic lupus erythematosus: a 10-year longitudinal validation study." Therapeutic Advances in Musculoskeletal Disease 14 (January 2022): 1759720X2210744. http://dx.doi.org/10.1177/1759720x221074451.
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Background: The fracture risk assessment tool has been widely used to stratify the 10-year fracture risk to guide therapy. Using the actual fracture data of a 10-year longitudinal cohort of older patients with systemic lupus erythematosus, we reported an underestimation of the tool in predicting major symptomatic osteoporotic fractures. Treatment of osteoporosis in systemic lupus erythematosus should not be based on fracture risk estimation alone. Relevant time-dependent risk factors should be taken into account for an individualized decision. Objective: To compare the observed fracture incidence in a 10-year longitudinal cohort of patients with systemic lupus erythematosus (SLE) with the fracture risk prediction from the fracture risk assessment (FRAX) tool. Methods: Adult patients (⩾40 years) with SLE who had a first DEXA scan performed in 2005–2009 were studied. The 10-year rates of major osteoporotic and hip fractures were estimated by FRAX using clinical data at DEXA with adjustment for prednisolone dosage. The actual incidence of clinical fractures at 10 years was compared with the estimated rates. Factors associated with new fractures were studied by logistic regression. Results: A total of 229 SLE patients were studied (age: 50.2 ± 6.6 years, 93% women). Glucocorticoid was used in 148 (65%) patients at baseline (mean dose: 7.3 ± 6.9 mg/day; 34% ⩾ 7.5 mg/day). Osteoporosis (bone mineral density T score ⩽ –2.5) at the hip, femoral neck, or spine was present in 61 (27%) patients. The estimated 10-year risk of major osteoporotic and hip fractures by FRAX was 3.4 ± 4.5% and 0.95 ± 2.3%, respectively. After 10 years, three patients developed hip fracture, 6 patients had limb fractures and 20 patients had symptomatic vertebral fractures (major osteoporotic fracture 12.7%, hip fracture 1.3%). The actual major osteoporotic fracture rate was significantly higher than the FRAX estimation (12.7% vs 3.4%; p < 0.001). Logistic regression revealed that osteoporosis (odds ratio (OR): 4.07 [1.51–10.9]), previous fragility fracture (OR: 3.18 [1.02–9.90]), and a parental history of fracture (OR: 4.44 [1.16–17.0]) were independently associated with new clinical fractures at 10 years. Conclusion: The FRAX tool underestimates the major clinical fracture risk at 10 years in patients with SLE.
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Fujiwara, Saeko. "Estimation of absolute risk for fracture." Nippon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics 46, no. 2 (2009): 128–30. http://dx.doi.org/10.3143/geriatrics.46.128.
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Binkley, Neil, and E. Michael Lewiecki. "The evolution of fracture risk estimation." Journal of Bone and Mineral Research 25, no. 10 (September 21, 2010): 2098–100. http://dx.doi.org/10.1002/jbmr.230.
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Kudlacek, S., B. Schneider, A. Resch, P. Bernecker, P. Pietschmann, R. Willvonseder, and H. Resch. "The fracture risk in males: Estimation of a fracture threshold." Bone 16, no. 3 (March 1995): 403. http://dx.doi.org/10.1016/8756-3282(95)90464-6.
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Mitchell, Paul James, and C. Chem. "Secondary prevention and estimation of fracture risk." Best Practice & Research Clinical Rheumatology 27, no. 6 (December 2013): 789–803. http://dx.doi.org/10.1016/j.berh.2013.11.004.
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Li, Wenjun, John Kornak, Tamara B. Harris, Joyce Keyak, Caixia Li, Ying Lu, Xiaoguang Cheng, and Thomas Lang. "Bone fracture risk estimation based on image similarity." Bone 45, no. 3 (September 2009): 560–67. http://dx.doi.org/10.1016/j.bone.2009.04.250.
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Saleh, C., M. Bukhari, and S. M. Bilgrami. "AB0913 PREDICTING PATIENTS AT RISK OF FRAGILITY FRACTURE WITH NORMAL BONE MINERAL DENSITY: AN OBSERVATIONAL STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1758.1–1758. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4544.
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Background:There is an increased risk of low-trauma fracture as bone mineral density (BMD) decreases, however a large proportion of these fragility fractures occur in those without osteoporosis or osteopenia. The widely used FRAX tool uses femoral neck (FN) BMD, amongst other parameters, to predict fracture risk. In those with normal BMD, data is lacking on the weight these other parameters hold in predicting future risk. Indeed, FN BMD can be facultative in the estimation of risk when using FRAX.Objectives:To establish predictors of fragility fracture in a patient cohort referred for BMD estimation, subsequently found to have bilateral FN BMD of greater than 1.Methods:A cohort of patients in the North West of England referred between 2004 and 2014 for BMD estimation, with both left and right FN BMD of greater than 1 were identified. Patient parameters identified and analysed included age at scan, gender, BMD at left hip, body mass index (BMI), fat mass, family history of fracture, alcohol history of 3 or more units per day, smoking status, rheumatoid arthritis (RA), and steroid exposure. Patients with fragility fracture were compared with those without fracture. Chi-square test and T-test were applied to categorical and continuous data respectively. Further univariate and multivariate logistic regression models were fitted to determine parameters associated with future fracture risk.Results:619 patients with bilateral FN BMD of greater than 1 were identified and included in analysis. Mean age at scan was 54 years (SD 11.82) and 542 (87.56%) were female. 92 (14.86%) patients had a fragility fracture. Mean left FN BMD was 1.91 (SD 0.71), and mean right FN BMD was 1.92 (SD 0.68). Results of the univariate analysis are described in Table 1 below.Table 1.Logistic regression analysis of patient parameters with unadjusted and adjusted odds ratios for fragility fracturePredictorUnadjusted odds ratio (95% CI)Odds ratio adjusted for age (95% CI)Odds ratio adjusted for age and gender (95% CI)Age at scan (years)0.99 (0.98-1.01)--Gender1.37 (0.66, 2.84)1.34 (0.64, 2.80)-BMD at left hip0.34 (0.03, 4.05)0.37 (0.03, 4.37)0.50 (0.03, 7.67)BMI1.07 (1.03, 1.10)1.07 (1.03, 1.10)1.07 (1.03, 1.10)Fat mass1.00 (1.00, 1.00)1.00 (1.00, 1.01)1.00 (1.00, 1.01)Parent fractured hip0.99 (0.57, 1.70)0.97 (0.56, 1.68)0.94 (0.54, 1.64)Alcohol (3 or more units/day)1.16 (0.47, 2.86)1.16 (0.47, 2.87)1.16 (0.47, 2.89)Current smoker1.40 (0.89, 2.21)1.40 (0.89, 2.21)1.42 (0.90, 2.23)Rheumatoid arthritis0.83 (0.32, 2.19)0.85 (0.32, 2.24)0.86 (0.34, 2.27)Steroid exposure0.53 (0.30, 0.96)0.53 (0.30, 0.96)0.54 (0.30, 0.98)Conclusion:Steroid exposure and body composition parameters influence fracture risk in this group pf patients with normal BMD, further work will be done looking at the types of fractures and other parameters in this group of patients.Disclosure of Interests:Christopher Saleh: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen and Novartis., Syed Mujtaba Bilgrami Speakers bureau: Pfizer
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Brook, S., G. Todorov, and A. N. Comninos. "65 Comparison of Frax and Qfracture in Predicting Fragility Fractures in Patients Presenting with Falls." Age and Ageing 50, Supplement_1 (March 2021): i12—i42. http://dx.doi.org/10.1093/ageing/afab030.26.
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Abstract Introduction Falls are a major risk factor for fragility fractures and patients should be appropriately assessed to reduce future fragility fracture risk. National guidelines provide recommendations on assessing fracture risk using calculators to guide therapy initiation. FRAX and QFracture are the two main calculators used, however they differ considerably in their inputs. The aim of this study was to compare the risk estimation and performance between these two frequently used calculators to help determine their appropriate utility. Methods Data from patients aged ≥70 years admitted with a fall to the Acute Medical Units at Charing Cross Hospital between 1st Dec 2018–31st March 2019 were retrospectively collected, covering all inputs required for the two risk calculators. The 10-year major osteoporotic and hip fracture risks were calculated using FRAX and QFracture and compared. The one-year major osteoporotic and hip fracture risks from QFracture were assessed against actual one-year fracture rates. Results Conclusions Risk calculators are effective tools to aid the decision of bone therapy initiation. Here we demonstrate that there is a strong correlation between the two commonly used calculators. However, in terms of absolute risk values there is a mean 8.9% difference with QFracture providing higher risks in this “fallers” group. As absolute treatment thresholds are frequently used to guide bone therapy initiation, opposing recommendations may result. Therefore, there is a need to further explore calculator performance and determine which would more accurately serve different patient groups.
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Dimić, Aleksandar, Stojanovic Sonja, Nedovic Jovan, Stankovic Aleksandra, Stamenkovic Bojana, Milenkovic Sasa, and Mitic Valentina. "Potential role of FRAX analysis in postmenopausal women with osteopenia." Open Medicine 6, no. 2 (April 1, 2011): 185–89. http://dx.doi.org/10.2478/s11536-011-0002-8.
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AbstractEarly diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis treatment. Dual-energy X-ray absorptometry (DXA) is a modern method for bone mineral density (BMD) evaluation. However, along BMD, clinical risk factors may significantly influence fracture development. Therefore, FRAX algorithm was designed for the assessment of a ten-year risk for serious osteoporotic fractures (SOF), as well as hip fractures. In the current study, we tried to evaluate the possible lumbal spine and hip BMD influence on ten year risk for SOF and hip fractures and potential role of FRAX in predicting the therapy in postmenopausal women with osteopenia. We performed the study on 385 postmenopausal women. According to the DXA measurements, at the lumbal (L) spine (L1–L4) and hip (femor neck), patients were then classified as normal, osteopenic, or osteoporotic. BMD evaluation included the L spine and the hip (subgroup 1), and only on the L spine (subgroup 2). By filling up the FRAX questionnaire, a ten-year risk for SOF fracture and hip fracture was calculated. BMD evaluation, in complete patient’s group and in subgroup 1, resulted in the highest number of osteoporosis (61.04%, 48.08%, retrospectively), while ospeopenia was a main finding in subgroup 2. In the subgroup 1, a high risk for SOF and hip fracture was detected in 16.45% and with high risk for hip fracture in 11.38% subjects. In subgroup 2, only high risk for hip fracture was observed in 3.16% subjects, indicating the active medicament treatment. Simultaneously, correlation of BMD results with FRAX values for SOF and hip fracture, showed significant negative correlation (p<0.001). Obtained results showed significant role of femur neck BMD evaluation in predicting the future factors, which may, together with FRAX analysis, improve the therapy approach in postmenopausal women with ospeopenia.
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Rato, M., F. Pinheiro, S. Garcia, B. M. Fernandes, S. Ganhão, R. Gaio, M. Bernardes, A. Bernardo, and L. Costa. "SAT0482 FRAX 10-YR FRACTURE RISK IN RHEUMATOID ARTHRITIS ASSESSED WITH AND WITHOUT BONE MINERAL DENSITY – ARE WE TREATING OUR PATIENTS UNDER bDMARDs?" Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1197.1–1198. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3354.
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Background:Patients with rheumatoid arthritis (RA) have a higher risk of osteoporosis not only due to chronic inflammation status, but also due to the treatment with glucocorticoids. FRAX is a computer-based algorithm developed by the World Health Organization for estimation of the 10-year risk of a hip or major osteoporotic fracture. Inclusion of femoral neck bone mineral density (BMD) in the estimation is optional.Objectives:The study aimed to identify the RA patients under treatment with biological disease-modifying antirheumatic drug (bDMARD), who have FRAX scores, calculated with and without BMD, classified as high fracture risk and evaluate if they are receiving treatment for osteoporosis. The authors also investigated the intra-individual agreement between FRAX fracture risk calculated with and without BMD.Methods:Demographic and clinical data and BMD results from RA patients followed in a tertiary university hospital and registered in the Rheumatic Diseases Portuguese Register were used for analysis. Patients under 40 years of age at the last visit were excluded. McNemar test was applied for the identification of discordance of risk categories. The Wilcoxon test was used to characterize the intraindividual differences between paired FRAX risks with and without BMD. Correlations between pairs of variables were evaluated by the Spearman test. For independent variables Mann-Whitney test was used.Results:A total of 303 patients were included, 244 were females (80.5%) and 49 current smokers (16.2%). Mean age was 59.5 ± 9.54 years and mean disease duration 18.5 ± 10.4 years. Two hundred and twenty patients (72.4%) and 243 (80.2%) were RF and ACPA positive, respectively, and 51.5% had erosive disease. Mean disease activity score (DAS28-4V-CRP) was 3.08 ± 1.18 and mean femoral neck BMD 0.84 ± 0.12 g/cm2. One hundred and seventy nine patients (58.9%) were concomitantly treated with conventional synthetic DMARDs and 215 (70.7%) with glucocorticoids. Among all the patients, 35 (11.6%) had previous fractures and 19 (6.3%) have family history of fracture. The median 10-year risk of a major fracture and a hip fracture, calculated without BMD, was 6.0 (1.2-50) and 1.5 (0.1-39), respectively; with BMD it was 6.9 (1.3-61) and 1.7 (0-49). When FRAX score is calculated without BMD (n=303), 76 (25.1%) patients were categorized as high fracture risk. Among them, only 41 (54%) were receiving osteoporosis treatment. FRAX assessment with BMD (n=231) identified 99 (32.7%) patients with high fracture risk, 51 (51,5%) in treatment for osteoporosis. Thirty patients (21%) previously classified as low fracture risk using FRAX without BMD were recategorized as high risk (p<0.001). Despite that, there was a strong correlation between fracture risks assessed with and without BMD for both major and hip fracture (r = 0.867, p < 0.0001 and r = 0.728, p < 0.0001, respectively). ACPA and RF positive patients did not have higher FRAX scores (including or not BMA). Patients with erosive disease had a higher 10-year probability of major fracture evaluated by FRAX when it includes BMD (p=0.041).Conclusion:It is very important to accurately assess the risk of osteoporotic fractures in RA patients to treat them properly. The authors highlight the high number of patients who are not receiving treatment according to FRAX categorization. In spite of the correlation between estimated fracture risk by FRAX with and without BMD, there is a discordance in fracture risk categorization, as one fifth of patients of low risk were reclassified as high risk. For the RA population treated with bDMARDS, our findings raise the need to request a DXA not only for patients classified as having an intermediate risk of fracture, but also for low-risk patients.Disclosure of Interests:Maria Rato: None declared, Filipe Pinheiro: None declared, Salomé Garcia: None declared, Bruno Miguel Fernandes: None declared, Sara Ganhão: None declared, Rita Gaio: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Alexandra Bernardo: None declared, Lúcia Costa: None declared
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Casciaro, Sergio, Maria Daniela Renna, Paola Pisani, Antonio Greco, Francesco Conversano, and Maurizio Muratore. "New Ultrasound-Based Methods for Early Osteoporosis Diagnosis and Fracture Risk Estimation." International Journal of Measurement Technologies and Instrumentation Engineering 4, no. 2 (April 2014): 24–38. http://dx.doi.org/10.4018/ijmtie.2014040103.
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Osteoporosis is the most common disorder of bone metabolism. The main consequence of this disease is the increased risk of fracture. Osteoporotic fractures represent a serious problem in terms of social and economic costs. Then, there is a strong need for the assessment of the best practices in prevention and treatment of osteoporosis. Dual X-ray absorptiometry (DXA) represents the current “gold standard” method for osteoporosis diagnosis. However, DXA cannot be employed for population mass screenings, because of required exposition to ionizing radiation and high management costs. The aim of this paper was to review the currently available techniques for osteoporosis diagnosis and also to illustrate the feasibility of an innovative quick, cheap and non-invasive ultrasound-based methodology. The results recently published by the authors' research group suggest that the proposed approach has the potential for routine application in early diagnosis, which is the key to resize the impact of osteoporosis on healthcare systems.
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Fernandes, B. M., S. Garcia, S. Ganhão, M. Rato, F. Pinheiro, M. Bernardes, and L. Costa. "SAT0465 FRACTURE RISK ASSESSMENT BY FRAX IN A SYSTEMIC LUPUS ERYTHEMATOSUS PORTUGUESE COHORT." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1189.1–1190. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2032.
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Background:Osteoporosis is commonly seen in patients with Systemic Lupus Erythematosus (SLE), even in pre-menopausal patients. The etiology is multifactorial and chronic glucocorticoid therapy seems to play a central role.Objectives:To investigate the ten-year risk of fracture assessed by Fracture Risk Assessment Tool (FRAX), with and without dual-energy X-ray absorptiometry (DXA) and to determine possible demographic or clinical factors associated with an increased risk of fracture in a SLE population.Methods:Retrospective study including all the over 40 years-old patients with the diagnosis of SLE (2012 SLICC classification criteria) followed at our Rheumatology Department registered in our national database. Demographic, clinical and laboratorial data were collected at the last follow-up visit. Data from the last DXA (until 3 years prior to the last visit) were collected. Indication for pharmacological treatment by FRAX was assessed according to the national recommendations: estimated fracture risk, without DXA, ≥11% for major osteoporotic fracture or ≥3% for hip fracture and/or estimated fracture risk, with DXA, ≥9% for major osteoporotic fracture or ≥2.5% for hip fracture.Results:We included 104 patients, 101 (97.1%) females, aged 54.5±9.9 years, with a median disease duration of 19.3 years [4.3-51.6]. Twelve patients (11.5%) were current smokers, 31 (29.8%) had elevated anti-dsDNA antibodies (≥100 IU/mL) and 27 (26.0%) had complement consumption (C3c<83mg/dL or C4<12mg/dL). 73 patients (70.2%) were taking glucocorticoids with a mean daily prednisolone equivalent dosage of 4.4±5.2 mg/day. Regarding SLE treatment, 69 patients (66.3%) were under hydroxychloroquine, 22 (21.2%) under azathioprine, 16 (15.4%) under mycophenolate mofetil, 5 (4.8%) under belimumab, 4 (3.8%) under methotrexate, 1 (1.0%) under leflunomide and 1 (1.0%) under rituximab.Ten patients (9.6%) had previous fragility fractures, 54 patients (51.9%) had DXA in the last 3 years and 81 (77.9%) were taking calcium and/or vitamin D supplements.Sixteen (15.4%) had indication for treatment by FRAX without DXA and 8 of these (50%) were under treatment. Moreover, thirteen (12.5%) had indication for treatment by FRAX with DXA and 8 of these (61.5%) were under treatment.Five patients (4.8%) were reclassified in FRAX with DXA: 3 patients (2.9%) had no indication for treatment by FRAX without DXA but conquered it by FRAX with DXA and 2 patients (1.9%) had indication for treatment by FRAX without DXA but lost it by FRAX with DXA. We found a good level of agreement in the indication for treatment between FRAX with and without DXA (kappa=0.741; p<0.001).There was no significant difference in the risk of fracture estimated by FRAX with or without DXA, both for major osteoporotic fracture and for hip fracture. Correlations between fracture risk and some clinical variables can be seen in table 1.Table 1.Correlations between the risk of fracture estimated by FRAX and disease related features.Age at SLE diagnosisDisease DurationESRSLEDAIEstimated fracture risk by FRAX:without DXAmajor osteoporotic fracturer=0.483p<0.001n.s.r=0.249p=0.012r=-0.586p=0.028hip fracturer=0.481p<0.001n.s.r=-0.552p=0.041n.s.with DXAmajor osteoporotic fracturer=0.386p=0.005r=0.299p=0.033n.s.n.s.hip fracturer=0.338p=0.015n.s.n.s.n.s.Conclusion:A higher number of patients had indication for pharmacological treatment by FRAX with DXA in comparison with FRAX without DXA. However, we found no statistically significant difference in the estimated fracture risk with and without DXA. This, together with the good level of agreement between FRAX with and without DXA, suggests that the fracture risk estimation, even without DXA, may be an appropriate approach. The low number of patients with indication for pharmacological treatment by FRAX, with and without DXA, may be explained by their low mean age and the high number of them under vitamin D/calcium supplementation.Disclosure of Interests:Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Sara Ganhão: None declared, Maria Rato: None declared, Filipe Pinheiro: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared
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Fernandes, B. M., S. Garcia, S. Ganhão, M. Rato, F. Pinheiro, M. Bernardes, and L. Costa. "SAT0449 SPONDYLOARTHRITIS AND FRACTURE RISK: DOES DXA REALLY HAVE AN IMPACT IN THE RISK OF FRACTURE ESTIMATED BY FRAX?" Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1181.1–1182. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1570.
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Background:Low bone mineral density (BMD) is common in ankylosing spondylitis (AS). The fracture risk (FR) is increased and its reduction with pharmacologic therapy is not clearly defined in this population. However, early screening and bisphosphonates as first-line treatment are recommended.Objectives:To investigate the influence of dual-energy X-ray absorptiometry (DXA) in the ten-year risk of fracture assessed by FR Assessment Tool (FRAX) and to determine possible demographic or clinical factors associated with an increased FR in a spondyloarthritis (SpA) population.Methods:Retrospective study including all the over 40 years-old SpA patients (ASAS classification criteria) followed at our Rheumatology Department and registered in the national database. Demographic, clinical and laboratorial data were collected at the time of the last follow-up visit. Data from the last DXA (until 3 years prior to the last visit) were collected. Indication for pharmacological treatment by FRAX was assessed according to the national recommendations.Results:A total of 231 SpA patients were included: 126 males (54.5%), 53 (22.9%) smokers; 171 (74%) had AS, 23 (10%) had Inflammatory Bowel Disease Associated SpA and 37 (16%) had Undifferentiated SpA. At the last follow-up visit, the mean age was 52.9 years (±9.6) and the median disease duration was 21.9 years [1.0-55.5]. The mean ASDAS-CRP was 2.5 (±0.9) and the majority of patients had moderate (25.5%) or high (48.5%) disease activity (according to ASDAS). One hundred and thirty patients (56.3%) were taking NSAIDs, 45 (19.5%) were taking glucocorticoids, 85 (36.8%) were under csDMARDs and 170 (73.6%) under bDMARDs [157 (68%) under TNFi, 11 (4.8%) under secukinumab and 2 (0.9%) under ustekinumab].Eleven patients (4.8%) had previous fragility fractures, 118 (51.1%) had DXA in the last 3 years and 167 (72.3%) were taking calcium and/or vitamin D supplements.Sixteen patients (6.9%) had indication for treatment by FRAX without DXA and 9 of these (56.3%) were already under treatment. Similarly, 16 (6.9%) had indication for treatment by FRAX with DXA and 13 of these (81.3%) were already under treatment. Ten patients (4.3%) were reclassified in FRAX with DXA: 7 (3%) had no indication for treatment by FRAX without DXA but obtained it by FRAX with DXA and 3 (1.3%) had indication for treatment by FRAX without DXA but they lost it by FRAX with DXA. We found a moderate level of agreement in the indication for treatment between FRAX with and without DXA (kappa=0.595; p<0.001). The use of DXA in FRAX estimated a significant higher median FR, both for major osteoporotic fracture (2.4% [0.8-31.0] vs 1.8% [0.6-20.0]; p<0.001) and for hip fracture (0.5% [0.0-23.0] vs 0.2% [0.0-14.0]; p<0.001).We found significant correlations between FR and some disease-related variables (table 1).Table 1.Correlations between the risk of fracture estimated by FRAX and disease-related variables.Disease durationBASDAIASDAS-CRPBASMIBASFIEstimated fracture risk by FRAX:without DXAmajor osteoporotic fracturer=0.352p<0.001r=0.204p=0.002r=0.214p=0.001r=0.301p<0.001r=0.317p<0.001hip fracturer=0.389p<0.001r=0.142p=0.034r=0.170p=0.011r=0.305p<0.001r=0.275p<0.001with DXAmajor osteoporotic fracturer=0.227p=0.014r=0.314p=0.001r=0.356p<0.001r=0.293p=0.002r=0.379p<0.001hip fracturen.s.r=0.197p=0.036r=0.269p=0.004r=0.271p=0.004r=0.258p=0.006Conclusion:Our results showed that a similar number of patients had indication for pharmacological treatment by FRAX both with and without DXA. Although the inclusion of DXA resulted in a higher estimated FR by FRAX, the observed moderate level of agreement between FRAX with and without DXA suggests that the FR estimation by FRAX, even without DXA, may be a reasonable approach in SpA patients. In line with literature, we found significant associations between the estimated risk fracture by FRAX and some disease activity and function measures.Disclosure of Interests:Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Sara Ganhão: None declared, Maria Rato: None declared, Filipe Pinheiro: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared
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Lems, Willem F. "Fracture risk estimation may facilitate the treatment gap in osteoporosis." Annals of the Rheumatic Diseases 74, no. 11 (September 25, 2015): 1943–45. http://dx.doi.org/10.1136/annrheumdis-2015-208245.
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Pouwels, Sander, Marloes T. Bazelier, Anthonius de Boer, Wim E. J. Weber, C. (Kees) Neef, Cyrus Cooper, and Frank de Vries. "Five-year fracture risk estimation in patients with Parkinson's disease." Bone 56, no. 2 (October 2013): 266–70. http://dx.doi.org/10.1016/j.bone.2013.06.018.
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Vako, Laoura R. "Additional tools for the estimation of fracture risk using DXA method." Journal of Research and Practice on the Musculoskeletal System 05, no. 04 (December 1, 2021): 140–46. http://dx.doi.org/10.22540/jrpms-05-140.
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Esposito, L., P. Bifulco, P. Gargiulo, M. K. Gíslason, M. Cesarelli, L. Iuppariello, H. Jónsson, A. Cutolo, and M. Fraldi. "Towards a patient-specific estimation of intra-operative femoral fracture risk." Computer Methods in Biomechanics and Biomedical Engineering 21, no. 12 (September 10, 2018): 663–72. http://dx.doi.org/10.1080/10255842.2018.1508570.
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Marchenkova, L. "POS1469-HPR THE ASSESSMENT OF FRACTURE RISK AND OSTEOPOROSIS RATE AMONG PATIENTS OVER 50 YEARS OLD UNDERGOING MEDICAL REHABILITATION." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1020.2–1020. http://dx.doi.org/10.1136/annrheumdis-2021-eular.4258.
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Background:Taking a course of physical rehabilitation creates the prerequisites for falls and injuries in patients at high risk of fractures. Data on fracture risk and prevalence of osteoporosis in older patients starting medical rehabilitation can change the approach of doctors to the development of rehabilitation programs and the management of such patients.Objectives:To assess the prevalence of osteoporosis, individual risk factors for osteoporosis as well as the proportion of people with high risk of osteoporotic low-energy fractures among patients over 50 years old undergoing treatment according to the “medical rehabilitation” profile.Methods:The study group comprised of 600 patients (426 women and 174 men) aged 50 to 84 years, average age 64.25 ± 10.17 years, undergoing treatment in a rehabilitation department. This was a cross-sectional study in the form of unified questionnaire, including data concerning age, weight, height, BMI, clinical and rehabilitation diagnosis, anamnesis of the main disease, anamnesis vitae, presence of osteoporosis diagnosis in the anamnesis, its treatment, osteoporosis risk factors estimation. An assessment of 10-year probability of osteoporotic fractures was carried out using Russian model of online FRAX® calculator.Results:41.8% patients in the study sample had osteoporosis risk factors, including 31.2% of subjects had 3 risk factors or more. 38.0% patients showed a high fracture risk according to the FRAX calculator. 34.1% had a diagnosis of osteoporosis, and 45.8% already had osteoporotic fractures. Among those who did not undergo densitometry examination, 69.9% had a history of low-traumatic fractures, and only 58.5% of patients with an established diagnosis of osteoporosis and 26.8% of those at high risk of fractures received effective therapy for osteoporosis.Conclusion:Population of patients over 50 years old undergoing rehabilitation is characterized by high frequency of osteoporosis and probability of fractures, and insufficient quality of osteoporosis verification and anti-osteoporotic therapy administration at the same time.Disclosure of Interests:None declared
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Guessous, Idris, Jacques Cornuz, Christiane Ruffieux, Peter Burckhardt, and Marc-Antoine Krieg. "Osteoporotic Fracture Risk in Elderly Women: Estimation with Quantitative Heel US and Clinical Risk Factors." Radiology 248, no. 1 (July 2008): 179–84. http://dx.doi.org/10.1148/radiol.2481070986.
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Lusenti, T., R. Rustichelli, P. Borgatti, P. Tansinda, L. Manenti, M. Gregorini, and G. Pioli. "Estimation of absolute fracture risk in renal transplant patients using FRAX tool." Bone 44 (June 2009): S391. http://dx.doi.org/10.1016/j.bone.2009.03.278.
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Sultan, Z., and M. Bukhari. "POS1141 FACTOR ANALYSIS OF FRAGILITY FRACTURES BY SITE IN PATIENTS REFERRED FOR DUAL-ENERGY X-RAY ABSORPTIOMETRY SCAN." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 899.2–899. http://dx.doi.org/10.1136/annrheumdis-2022-eular.662.
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BackgroundFragility fractures are defined as fractures which occur secondary to low energy trauma (1). Fractures lead to substantial pain, reduced quality of life and significant burden to society, with 3.5 million fragility fractures occurring in the EU in 2010 costing €37 billion (2). It is predicted that by 2025 this cost will have increased by 25% (2). Studying fractures is in the interest of our ageing society in order to aid management of patients at risk. To our knowledge, no other studies have grouped fractures based on site by factor analysis.Objectives1.Determine which fractures are most common in patients who present for dual-energy X-ray absorptiometry (DEXA) scan2.Apply a factor analysis to establish any patterns in the incidence of fractures based on siteMethodsBetween 1996 and 2017, 31546 patients presented to a district general hospital in the North West of England for bone mineral density estimation by DEXA scan. Demographic details, risk factors, incidence of fractures and site of fractures were recorded at time of scan. These data were retrospectively studied to identify patients who had sustained at least one fracture. STATA was used to conduct a factor analysis using the principal component factors (PCF) method. Ethical approval was granted by the Northwest Regional Ethics Committee.Results11839 patients were identified to have had at least one fracture (14756 total fractures). Mean age was 67.96, with 9993 females and 1846 males. Mean height was 161.21 cm, mean weight was 70.41 kg and mean BMI was 27.04 kg/m2. Mean T-scores at femoral neck, total femur and lumbar spine were -1.55, -1.38 and -1.30 respectively. The most common fracture site was at the wrist/forearm with 5421 (36.74%) cases. Further, there were 2795 tibia/fibula (18.94%), 2530 spine (17.15%), 1363 femur (9.24%), 1224 humerus (8.29%), 1063 rib (7.20%), 315 pelvis (2.13%), 43 elbow (0.29%) and 2 ankle (0.01%) fractures. 9390 patients had 1 fracture and 2449 patients had more than 1, with 9 patients sustaining 5 fractures. Factor analysis on fracture sites revealed 6 factors with an eigenvalue > 1. Fracture sites were grouped together based on those fractures which loaded most heavily on each factor. Loading was as follows: spine and ribs on Factor 1; spine, pelvis and wrist/forearm on Factor 2; humerus and femur on Factor 3; elbow and ankle on Factor 4; ribs and humerus on Factor 5; ribs and femur on Factor 6 (Table 1).Table 1.Factor analysis on sites of fractures using the PCF method.VariableFactor 1Factor 2Factor 3Factor 4Factor 5Factor 6UniquenessTibia/fibula0.0862-0.9485-0.05300.11820.0325-0.08960.0671Spine0.69060.3263-0.4535-0.1501-0.2681-0.18370.0829Ribs0.21280.1089-0.0689-0.09570.75350.60740.0193Pelvis0.08100.20500.1185-0.01580.2113-0.36630.7368Humerus0.03860.14330.55780.08920.3832-0.51010.2518Femur0.12270.09460.70520.0071-0.48140.45320.0416Elbow0.03970.1300-0.07400.73060.03050.03630.4401Ankle0.05470.1082-0.10840.7189-0.03650.07160.4503Wrist/forearm-0.88560.2389-0.2461-0.0479-0.06080.00710.0920ConclusionIn-keeping with published data, the most common site for fracture was forearm (3). Factor analysis grouped together sites of fractures into 6 factors, suggesting that these fractures are more likely to co-exist. Moving forward it would be beneficial to ascertain differences between the groups in terms of demographics, risk factors and any bone protection measures taken. This may highlight clinically relevant data in order to make evidence based decisions in the identification and management of patients at risk of fragility fractures.References[1]National Institute for Health and Care Excellence (NICE). Osteoporosis: assessing the risk of fragility fracture - Clinical Guideline (CG146). 2012;(August)[2]Svedbom A. et al. Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos (2013) 8:137[3]Johnell, O., Kanis, J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17, 1726–1733 (2006)Disclosure of InterestsNone declared
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Marchenkova, Larisa A., Ekaterina V. Makarova, Marina Yu Gerasimenko, and Inna S. Evstigneeva. "Assesment of osteoporotic fractures risk and osteoporosis prevalence among patients over 50 years old undergoing medical rehabilitation." Russian Journal of Physiotherapy, Balneology and Rehabilitation 19, no. 1 (October 23, 2020): 13–19. http://dx.doi.org/10.17816/1681-3456-2020-19-1-2.
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Background. Back pain, limitation of mobility, spinal deformity, decreased ability to self-care due to osteoporotic fractures (vertebrae, femoral neck, humerus, etc.) are one of the reasons for referring patients to rehabilitation and rehabilitation treatment, which involves the use of physical therapy methods, physiotherapy exercises and mechanotherapy.
Objective: to assess the prevalence of osteoporosis (OP), individual risk factors for OP, as well as the proportion of people with high risk of osteoporotic low-energy fractures among patients over 50 years old undergoing treatment according to the medical rehabilitation profile.
Methods. The study group comprised of 600 patients (426 women and 174 men) aged 50 to 84 years, average age 64.2510.17 years, undergoing treatment in a rehabilitation department. This was a cross-sectional study in the form of unified questionnaire, including data conserning age, weight, height, BMI, clinical and rehabilitation diagnosis, anamnesis of the main disease, anamnesis vitae, presence of OP diagnosis in the anamnesis, its treatment, OP risk factors estimation. An assessment of 10-year probability of osteoporotic fractures was carried out using Russian model of online FRAX calculator.
Results. 41.8% patients in the study sample had OP risk factors, including 31.2% ― 3 risk factors or more. 38% patients over 50 years old undergoing medical rehabilitation showed a high fracture risk according to the FRAX calculator. 34.1% had a diagnosis of OP stated, and 45.8% already had osteoporotic fractures. Among those who did not undergo densitometry examination, 69.9% had a history of low-traumatic fractures, and only 58.5% of patients with an established diagnosis of OP and 26.8% of those at high risk of fractures received effective therapy for OP.
Conclusion. Among patients over 50 years old undergoing medical rehabilitation a high frequency of OP and high fracture risk were stated. At the same time, insufficient quality of OP diagnostics and anti-osteoporotic therapy administaration were revealed.
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Shubinsky, I. B., A. M. Zamyshliaev, A. N. Ignatov, A. I. Kibzun, and E. O. Novozhilov. "Method of identification of the ranges of (non)acceptable factor values to reduce the risk of freight car derailment due to broken bogie solebar." Dependability 19, no. 3 (September 17, 2019): 40–46. http://dx.doi.org/10.21683/1729-2646-2019-19-3-40-46.
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Aim. According to the Russian freight car crash/derailment investigation records for the period between 2013 and 2016., derailments and crashes during train operations were mostly caused by rolling stock malfunctions, while about a third of such derailments were due to bogie solebar fracture. The average number of derailed units of rolling stock is 4.16 in case of derailment due to solebar fracture against 1.73 in case of derailments due to other rolling stock malfunctions. Previously, a method was developed that allows making decisions to discard a batch of solebars. On the other hand, solebars from batches exempt from discarding can be subject to fractures over time. In this context, it appears to be of relevance to develop a method that would enable timely uncoupling of a car for its submission to depot/full repairs in order to avoid solebar fracture. For this purpose, factor models of fracture hazard estimation should be considered. Such factors may include the number of kilometers travelled from the last maintenance depot (MD), as well as the number of kilometers and days until the next scheduled full/depot repairs. The probability of solebar fracture can be used as the quantitative characteristic of the hazard of solebar fracture. However, probability estimation in the form of, for instance, the frequency of solebar fracture is only possible when observation data is available on when fracture or critical defect of solebar did not occur, yet such data is not collected. Therefore, the hazard index of solebar fracture should be developed. As it is difficult to manage the frequency of car submission to MD, the hazard index must depend only on the number of days and kilometers to repairs. Using the constructed index, the ranges of (non) acceptable factor values must be defined in order to enable decision-making regarding car uncoupling and submission to repairs, should the MD car inspector have doubts regarding the necessity of uncoupling. Methods. Methods of mathematical programming were used in this paper. Results. Conclusions. An impact index was built that characterizes the probability of freight car solebar fracture depending on the number of days and kilometers until the next scheduled repairs of such car. Based on that index, two methods of definition of ranges of (non)acceptable factor values were proposed. The first method was based on the values of the impact index. The second one was based on the identification of some parameters of ranges of (non)acceptable factor values and selection – out of all ranges – of the best ones in terms the lowest hazard of solebar fracture. Such selection was made by solving problems of mixed integer programming with quadratic constraint.
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Alcântara, Amadeus C. S., Israel Assis, Daniel Prada, Konrad Mehle, Stefan Schwan, Lúcia Costa-Paiva, Munir S. Skaf, Luiz C. Wrobel, and Paulo Sollero. "Patient-Specific Bone Multiscale Modelling, Fracture Simulation and Risk Analysis—A Survey." Materials 13, no. 1 (December 24, 2019): 106. http://dx.doi.org/10.3390/ma13010106.
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This paper provides a starting point for researchers and practitioners from biology, medicine, physics and engineering who can benefit from an up-to-date literature survey on patient-specific bone fracture modelling, simulation and risk analysis. This survey hints at a framework for devising realistic patient-specific bone fracture simulations. This paper has 18 sections: Section 1 presents the main interested parties; Section 2 explains the organzation of the text; Section 3 motivates further work on patient-specific bone fracture simulation; Section 4 motivates this survey; Section 5 concerns the collection of bibliographical references; Section 6 motivates the physico-mathematical approach to bone fracture; Section 7 presents the modelling of bone as a continuum; Section 8 categorizes the surveyed literature into a continuum mechanics framework; Section 9 concerns the computational modelling of bone geometry; Section 10 concerns the estimation of bone mechanical properties; Section 11 concerns the selection of boundary conditions representative of bone trauma; Section 12 concerns bone fracture simulation; Section 13 presents the multiscale structure of bone; Section 14 concerns the multiscale mathematical modelling of bone; Section 15 concerns the experimental validation of bone fracture simulations; Section 16 concerns bone fracture risk assessment. Lastly, glossaries for symbols, acronyms, and physico-mathematical terms are provided.
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Grassi, Lorenzo, Sami P. Väänänen, and Hanna Isaksson. "Statistical Shape and Appearance Models: Development Towards Improved Osteoporosis Care." Current Osteoporosis Reports 19, no. 6 (November 13, 2021): 676–87. http://dx.doi.org/10.1007/s11914-021-00711-w.
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Abstract Purpose of Review Statistical models of shape and appearance have increased their popularity since the 1990s and are today highly prevalent in the field of medical image analysis. In this article, we review the recent literature about how statistical models have been applied in the context of osteoporosis and fracture risk estimation. Recent Findings Recent developments have increased their ability to accurately segment bones, as well as to perform 3D reconstruction and classify bone anatomies, all features of high interest in the field of osteoporosis and fragility fractures diagnosis, prevention, and treatment. An increasing number of studies used statistical models to estimate fracture risk in retrospective case-control cohorts, which is a promising step towards future clinical application. Summary All the reviewed application areas made considerable steps forward in the past 5–6 years. Heterogeneities in validation hinder a thorough comparison between the different methods and represent one of the future challenges to be addressed to reach clinical implementation.
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Lukyanets, E. Yu. "Estimation of bone mineral density and algorithms of 10-year risk of osteoporotic fractures in women." Medicine of Ukraine, no. 5(251) (July 16, 2021): 31–34. http://dx.doi.org/10.37987/1997-9894.2021.5(251).238139.
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Osteoporosis is the fourth most common after cardiovascular, cancer and endocrine diseases. With an increase in life expectancy, it becomes one of the main causes of deterioration in health and an increase in mortality.
Aim of the study. Assess bone mineral density using ultrasonic densitometry and the risk of osteoporotic fractures among women in Cherkasy region.
Materials and methods. The study was based on a survey of 43 women in the Odessa region, the average age of the subjects was 56,4±9,9 years, the average body weight was 73,5±11,6 kg, height 164,9±5,9 cm, the average BMI was 27,1±4,3. All women were divided into groups by age with a ten-year interval and by densitometry indices.
Results. Decreased bone density was found in 58,1 % of subjects, osteoporosis - 2 (4,8%). Women with osteopenia and osteoporosis have an increased risk of fractures and significantly reduced ultrasound densitometry compared to respondents with normal BMD. The structure of concomitant pathology was dominated by diseases of the circulatory system (22 cases;51,2 %) and digestive organs (12; 27,9 %). More than half of women (26; 60,5 %) had a total of 50 comorbidities, with an average of 1.2 cases of comorbidity.
Conclusions. Most women had osteopenic manifestations. Age significantly correlates with BMD parameters. The number of women with changes in the structure of bone tissue increases with age. Algorithms for assessing the 10-year risk of FRAX and Q-Fracture fractures are significantly correlated with densitometry. The combination of ultrasonic densitometry with algorithms for assessing the risk of osteoporotic fractures increases the diagnosis of osteoporosis.
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Lukyanets, E. Yu. "Estimation of bone mineral density and algorithms of 10-year risk of osteoporotic fractures in women." Medicine of Ukraine, no. 4(260) (July 1, 2022): 17–20. http://dx.doi.org/10.37987/1997-9894.2022.4(260).271627.
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Osteoporosis is the fourth most common after cardiovascular, cancer and endocrine diseases. With an increase in life expectancy, it becomes one of the main causes of deterioration in health and an increase in mortality.
Aim of the study. Assess bone mineral density using ultrasonic densitometry and the risk of osteoporotic fractures among women in Cherkasy region.
Materials and methods. The study was based on a survey of 43 women in the Odessa region, the average age of the subjects was 56,4±9,9 years, the average body weight was 73,5±11,6 kg, height 164,9±5,9 cm, the average BMI was 27,1±4,3. All women were divided into groups by age with a ten-year interval and by densitometry indices.
Results. Decreased bone density was found in 58,1 % of subjects, osteoporosis - 2 (4,8%). Women with osteopenia and osteoporosis have an increased risk of fractures and significantly reduced ultrasound densitometry compared to respondents with normal BMD. The structure of concomitant pathology was dominated by diseases of the circulatory system (22 cases;51,2 %) and digestive organs (12; 27,9 %). More than half of women (26; 60,5 %) had a total of 50 comorbidities, with an average of 1.2 cases of comorbidity.
Conclusions. Most women had osteopenic manifestations. Age significantly correlates with BMD parameters. The number of women with changes in the structure of bone tissue increases with age. Algorithms for assessing the 10-year risk of FRAX and Q-Fracture fractures are significantly correlated with densitometry. The combination of ultrasonic densitometry with algorithms for assessing the risk of osteoporotic fractures increases the diagnosis of osteoporosis.
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Adami, G., A. Fassio, A. Giollo, G. Orsolini, O. Viapiana, D. Gatti, and M. Rossini. "SAT0456 REAL-LIFE RISK OF FRACTURE AND TREATMENT PREVALENCE IN DRUG-INDUCED OSTEOPOROSIS IN ITALY USING A NEW ALGORITHM." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1185.1–1186. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2565.
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Background:Glucocorticoid-induced osteoporosis and osteoporosis induced by adjuvant hormone therapy for breast cancer are the most common forms of secondary osteoporosis.Objectives:The exact real-life prevalence of treatment with anti-osteoporotic drugs in women with drug-induced osteoporosis is not known. In the present study, using a new mathematical and computerized algorithm, we investigate the profile of risk of fracture of women with drug-induced osteoporosis and the prevalence of treatment with anti-osteoporotic drugs.Methods:We have retrospectively analyzed the 10-year risk of major osteoporotic fracture calculated with the DeFRAcalc79 tool in postmenopausal women aged over 50 years that were initiating an anti-osteoporotic treatment (fully reimbursed according to the Nota 79). DeFRAcalc79 is a new web-based fracture risk-assessment tool (https://defra-osteoporosi.it) that arithmetically adjusts the risk based on multiple risk factors contemplated by the Nota 79, which regulates the reimbursability for osteoporosis medications in Italy (Italian Agency for Drugs, AIFA), including demographic and anthropometric data, femoral and/or lumbar spine BMD T-score, family history of femoral or vertebral fractures, number and site of previous osteoporotic fracture (including vertebral, femoral, and non-vertebral non-femoral fractures), glucocorticoid treatment (> 3 or > 12 months, ≥5 mg prednisone or equivalent), adjuvant hormone therapy for breast cancer, and comorbidities that induce an increased risk of fracture (rheumatoid arthritis and other connective tissue diseases, chronic obstructive pulmonary disease, inflammatory bowel diseases, Parkinson’s disease, multiple sclerosis, human immunodeficiency virus infection, diabetes, or severe physical handicap). This is a sub-analysis of the cross-sectional observational study to validate and further develop the DeFRA algorithm for the estimation of the risk of osteoporotic fractures, promoted by Verona hospital with the unconditional support of Amgen Srl.Results:Among 208 women, 116 (55.8%) were treated with adjuvant hormone therapy for breast cancer and 92 (44.2%) were on glucocorticoid ≥5 mg/day. Women on glucocorticoids had a greater mean 10-year risk of fracture compared to women on adjuvant hormone therapy for breast cancer (67.0% vs 39.1% p<0.01). 50.7% of women on adjuvant hormone therapy for breast cancer used denosumab, 28.0% zoledronic acid and 17.3% alendronate. In glucocorticoid-induced osteoporosis, 17.6% of the women used teriparatide, 37.3% alendronate, 29.4% zoledronic acid and 13.7% denosumab.Conclusion:In our cohort of patients, treatment with adjuvant hormone therapy for breast cancer was slightly more common than glucocorticoids. Women with glucocorticoid-induced osteoporosis had a greater risk of fracture compared to patients treated with adjuvant hormone therapy for breast cancer. Half of the patients on adjuvant hormone therapy for breast cancer were prescribed with denosumab. One-fifth of the patients with glucocorticoid-induced osteoporosis was treated with teriparatide. DeFRAcalc79 is a useful and practical tool for the integrated evaluation of fracture risk in drug-induced osteoporosis.Disclosure of Interests:Giovanni Adami: None declared, Angelo Fassio Speakers bureau: Angelo Fassio reports personal fees from: Abiogen and Novartis, outside the submitted work., Alessandro Giollo: None declared, Giovanni Orsolini: None declared, Ombretta Viapiana: None declared, Davide Gatti Speakers bureau: Davide Gatti reports personal fees from Abiogen, Amgen, Janssen-Cilag, Mundipharma, outside the submitted work., Maurizio Rossini Speakers bureau: AbbVie, Abiogen, Amgen, BMS, Eli-Lilly, Novartis, Pfizer, Sanofi, Sandoz and UCB
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Conversano, F., P. Pisani, A. Greco, G. Soloperto, M. Muratore, and S. Casciaro. "SAT0468 An Innovative Ultrasound-Based Method for the Estimation of Osteoporotic Fracture Risk." Annals of the Rheumatic Diseases 73, Suppl 2 (June 2014): 763.1–763. http://dx.doi.org/10.1136/annrheumdis-2014-eular.5400.
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Veenland, J. F., T. M. Link, W. Konermann, N. Meier, J. L. Grashuis, and E. S. Gelsema. "Comparison of two fractal dimension estimation methods in predicting fracture risk in vertebrae." Osteoporosis International 6, S1 (January 1996): 146. http://dx.doi.org/10.1007/bf02500123.
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Gnudi, S., G. Gualtieri, and N. Malavolta. "Simultaneous densitometry and quantitative bone sonography in the estimation of osteoporotic fracture risk." British Journal of Radiology 71, no. 846 (June 1998): 625–29. http://dx.doi.org/10.1259/bjr.71.846.9849385.
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Manning, Louise I., Andrew M. Briggs, Sharon Van Doornum, Ashwini Kale, Susan Kantor, and John D. Wark. "Glucocorticoid-Induced Bone Loss Is Associated with Abnormal Intravertebral Areal Bone Mineral Density Distribution." International Journal of Endocrinology 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/768579.
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Individuals with glucocorticoid-induced osteoporosis experience vertebral fractures at an increased rate and at higher vertebral areal bone mineral density (aBMD) than individuals with primary osteoporosis. Standard posteroanterior- (PA-) projection dual energy X-ray absorptiometry (DXA) lacks the diagnostic sensitivity required for reliable estimation of vertebral fracture risk in individuals. Assessment of subregional vertebral aBMD using lateral-projection DXA may improve the predictive value of DXA parameters for fracture. One hundred and four individuals were recruited and grouped for this study: primary osteoporosis with no history of vertebral fracture (n=43), glucocorticoid-induced bone loss (n=13), and healthy controls (n=48). Standard PA-projection and supine-lateral scans were performed, and lateral scans were analysed according to an established protocol to measure aBMD within 6 subregions. Main effects for subregion and group were assessed and observed, by ANCOVA. Ratios were calculated between subregions and compared between groups, to overcome the potentially confounding influence of variability in subregional geometry. Significantly lower values were observed in the glucocorticoid group for the ratios of (i) anterior subregion: whole vertebral body and (ii) posterior: whole vertebral body when compared to the primary osteoporosis and control groups (P<0.05). Lower anterior subregional aBMD in individuals on glucocorticoid therapy may help to explain the increased vertebral fracture risk in this patient group.
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So, Jacqueline, and Chi Chiu Mok. "Glucocorticoid-Induced Osteoporosis: The Potential Role of Romosozumab." Journal of Clinical Rheumatology and Immunology 20, no. 02 (December 2020): 71–79. http://dx.doi.org/10.1142/s2661341720300074.
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Glucocorticoid (GC)-induced osteoporosis (GIOP) is a major problem in patients with rheumatic diseases. The deleterious effect of GC on bone turnover is rapid and dose-dependent, with a predilection on the trabecular bone, resulting in vertebral fractures. Early recognition and prompt treatment of GIOP helps prevent bone loss and reduce fractures. There are pitfalls in current assessment tools for GIOP by dual-energy X-ray absorptiometry (DXA) and fracture risk assessment tool (FRAX) estimation formula. In this review, we evaluate different assessment methods for GIOP and summarize current therapies of GIOP, including the antiresorptive and anabolic agents. The potential role of newer anti-osteoporosis agent romosozumab, an anti-sclerostin monoclonal antibody, is also discussed.
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Lam, Ming-Tuen, Chor-Wing Sing, Gloria H. Y. Li, Annie W. C. Kung, Kathryn C. B. Tan, and Ching-Lung Cheung. "Development and Validation of a Risk Score to Predict the First Hip Fracture in the Oldest Old: A Retrospective Cohort Study." Journals of Gerontology: Series A 75, no. 5 (July 29, 2019): 980–86. http://dx.doi.org/10.1093/gerona/glz178.
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Abstract Background To evaluate whether the common risk factors and risk scores (FRAX, QFracture, and Garvan) can predict hip fracture in the oldest old (defined as people aged 80 and older) and to develop an oldest-old-specific 10-year hip fracture prediction risk algorithm. Methods Subjects aged 80 years and older without history of hip fracture were studied. For the derivation cohort (N = 251, mean age = 83), participants were enrolled with a median follow-up time of 8.9 years. For the validation cohort (N = 599, mean age = 85), outpatients were enrolled with a median follow-up of 2.6 years. A five-factor risk score (the Hong Kong Osteoporosis Study [HKOS] score) for incident hip fracture was derived and validated, and its predictive accuracy was evaluated and compared with other risk scores. Results In the derivation cohort, the C-statistics were .65, .61, .65, .76, and .78 for FRAX with bone mineral density (BMD), FRAX without BMD, QFracture, Garvan, and the HKOS score, respectively. The category-less net reclassification index and integrated discrimination improvement of the HKOS score showed a better reclassification of hip fracture than FRAX and QFracture (all p < .001) but not Garvan, while Garvan, but not HKOS score, showed a significant over-estimation in fracture risk (Hosmer–Lemeshow test p < .001). In the validation cohort, the HKOS score had a C-statistic of .81 and a considerable agreement between expected and observed fracture risk in calibration. Conclusion The HKOS score can predict 10-year incident hip fracture among the oldest old in Hong Kong. The score may be useful in identifying the oldest old patients at risk of hip fracture in both community-dwelling and hospital settings.
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Reddy, Gowry, Priya Rathi, Unnikrishnan B., Surendra Kamath, and Kalpita Shringapure. "Are other feasible options available for screening of risk assessment of osteoporosis in postmenopausal women at community level in Southern Coastal India." International Journal Of Community Medicine And Public Health 6, no. 1 (December 24, 2018): 123. http://dx.doi.org/10.18203/2394-6040.ijcmph20185142.
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Background: Osteoporosis is a chronic debilitating condition which exhibits iceberg phenomenon. Identification at an early stage of disease will enable preventive measures to reduce the incidence of disease and complications. Owing to the cost of diagnostic test, this study, various screening tools such as WHO fracture risk assessment tool, osteoporosis self-assessment tool for Asians, simple calculated osteoporosis risk estimation and osteoporosis risk assessment instrument have been used for assessment, in order to screen postmenopausal women in the preliminary stages.Methods: A facility-based cross-sectional study was conducted among 107 postmenopausal women carried over a period of five months.Results: Prevalence of osteoporosis and osteopenia was 24.3% and 69.2%. The area under the curve for osteoporosis self-assessment tool for Asians (OSTA), simple calculated osteoporotic risk estimation (SCORE) and osteoporotic risk assessment instrument (ORAI) was 0.731, 0.407 and 0.172 respectively. OSTA proved to be effective in differentiating normal BMD from low BMD score (i.e., osteopenia and osteoporosis) with a cut off of 1.1, SCORE to be more effective in screening osteoporosis than the other tools because it had a higher positive probability with a cut off 22. FRAX tool predicted probability of five and three percent probability of major fracture and hip fracture risk in ten yearsConclusions: Various tools assessed in the studies can be utilized at community level for identifying high risk women in post-menopausal stage but with different cut offs. This will reduce the cost of screening and also facilitate non pharmacological measures to reduce the progression of disease.
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Eller-Vainicher, Cristina, Alberto Falchetti, Luigi Gennari, Elisa Cairoli, Francesco Bertoldo, Fabio Vescini, Alfredo Scillitani, and Iacopo Chiodini. "DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders." European Journal of Endocrinology 180, no. 6 (June 2019): R213—R232. http://dx.doi.org/10.1530/eje-18-0991.
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An underlying disease affecting bone health is present in up to 40 and 60% of osteoporotic postmenopausal women and men respectively. Among the disorders leading to a secondary form of osteoporosis, the endocrine diseases are highly represented. A frequent finding in patients affected with an endocrine-related forms of bone disease is that the skeletal fragility is partially independent of the bone density, since the fracture risk in these patients is related more to a reduction of bone quality than to a decrease of bone mass. As a consequence, bone mineral density evaluation by dual-X-ray absorptiometry may be inadequate for establishing the risk of fracture in the setting of the endocrine-related forms of osteoporosis. In the recent years, several attempts to non-invasively estimating bone quality have been done. Nowadays, some new tools are available in the clinical practice for optimising the fracture risk estimation in patients with endocrine disorders. The aim of this review is to summarise the evidence regarding the role of the different imaging tools for evaluating bone density and bone quality in the most frequent forms of endocrine-related osteoporosis, such as obesity, diabetes, acromegaly, thyrotoxicosis, primary hyperparathyroidism, hypercortisolism and hypogonadism. For each of these disorders, data regarding both the current available tools and the future possible new techniques for assessing bone fragility in patients with endocrine diseases are reported.
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Riar, Shivraj, A. Lynn Feasel, Fariba Aghajafari, Dean Frohlich, Christopher J. Symonds, Greg A. Kline, and Emma O. Billington. "Comparison of 2 fracture risk estimation processes in Alberta: a cross-sectional chart review." CMAJ Open 9, no. 2 (April 2021): E711—E717. http://dx.doi.org/10.9778/cmajo.20200207.
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KANAZAWA, Hideyasu, Jiro SAKAMOTO, Serina AWAMORI, Taizo HATOU, Hideki MURAKAMI, Norio KAWAHARA, Juhachi ODA, and Kasturo TOMITA. "A Study of Vertebral Fracture Risk Estimation in Osteoporosis by Image-Based Finite-Element." Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME 2003.15 (2003): 393–94. http://dx.doi.org/10.1299/jsmebio.2003.15.393.
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Hopkins, R. B., E. Pullenayegum, R. Goeree, J. D. Adachi, A. Papaioannou, W. D. Leslie, J. E. Tarride, and L. Thabane. "Estimation of the lifetime risk of hip fracture for women and men in Canada." Osteoporosis International 23, no. 3 (May 11, 2011): 921–27. http://dx.doi.org/10.1007/s00198-011-1652-8.
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Moayyeri, Alireza. "The importance and applications of absolute fracture risk estimation in clinical practice and research." Bone 45, no. 2 (August 2009): 154–57. http://dx.doi.org/10.1016/j.bone.2009.03.666.
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Nogata, Fumio, Akira Shimamoto, and Toshihiko Habu. "Estimation of In Vivo Bone Strength Using Ultrasound Signals." International Journal of Modern Physics B 17, no. 08n09 (April 10, 2003): 1381–87. http://dx.doi.org/10.1142/s0217979203019034.
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A new method for estimating in vivo bone strength using ultrasound inspection is described, which can allow diagnose of osteoporosis from the viewpoint of mechanical integrity. The method was based on the two-dimensional area fraction of bone calculated from the difference in the speed of ultrasound propagation through cancellous bone. Then bulk Young's modulus was calculated for various architectures of the cancellous bone with the bone area fraction (S) using finite element method. Since there was a good relationship between the BMD (bone mineral density) by DXA (dual energy x-ray absorptiometry) method and the bone area fraction by ultrasound inspection, the technique also allows the estimation of in vivo BMD of the spine, which has been traditionally used at medical area to diagnose osteoporosis. Note that the periodic estimation of the bulk Young's modulus and strength applying the technique is effective to predict the fracture risk for in vivo bone.
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Takegami, Hiroaki, Atsuhiko Terada, Kaoru Onuki, and Ryutaro Hino. "Fracture strength estimation of SiC block for IS process." Nuclear Engineering and Design 241, no. 12 (December 2011): 4726–30. http://dx.doi.org/10.1016/j.nucengdes.2011.03.035.
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Xuan, Fu-Zhen, Shan-Tung Tu, and Zhengdong Wang. "Time-Dependent Fracture and Defect Assessment of Welded Structures at High Temperature." Journal of Pressure Vessel Technology 128, no. 4 (November 30, 2005): 556–65. http://dx.doi.org/10.1115/1.2349567.
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The present work reports several new insights into creep crack growth performance and defect assessment of welded structures at elevated temperature. First of all, an equivalent homogeneous model based on the limit load analysis is proposed to reflect the mismatch effects of the base and weld metals, the geometrical dimension of weldment constituents and the location of the pre-existing defects. Secondly, using the proposed equivalent homogeneous model, an estimation methodology for the time-dependent fracture mechanics parameter C* is developed in conjunction with the reference stress (RS) method and the GE/EPRI scheme. Such an estimation method was validated by using nonlinear finite element analysis of 48 compact tension (CT) specimens with various degrees of mismatch in creep behavior and different width of the welding seam. After that, the applicability of C* measurement recommended in ASTM E 1457 is re-examined for the CT specimen with a mismatched cross-weld. From the limit load analysis, a series of modifications for experimental C* estimation equation from ASTM E 1457 is introduced based on the proposed equivalent homogeneous model. Finally, a failure assessment diagram (FAD)-based method is presented for the welded structures at high temperatures. The application of such an approach to a welded cylinder with an internal circumference crack under axial tension is also reported in this paper.
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Dey, M., and M. Bukhari. "OP0324 CLUSTERING OF FRAGILITY FRACTURES BY SITE IN PATIENTS REFERRED FOR BONE MINERAL DENSITY ESTIMATION: AN OBSERVATIONAL STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 199.2–199. http://dx.doi.org/10.1136/annrheumdis-2020-eular.856.
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Background:Fragility fractures (FF) are those resulting from mechanical forces equivalent to a fall from standing height or less [1]. They most commonly occur in the spine (vertebrae), forearm, and femur, but also occur at other sites. Prevalence markedly increases with age, due to age-related and menopause-related bone loss. FF cause substantial pain and disability, and are associated with decreased life expectancy. While many studies have investigated risk factors associated with FF, there are few data on the association between FF sites in at-risk patients.Objectives:1. Establish the most common sites of FF in patients presenting for bone mineral density (BMD) estimation.2. Identify patterns of co-existing FF in the above cohort by applying cluster analysis.Methods:We retrospectively reviewed the clinical records of 28868 patients presenting for BMD estimation at a district general hospital in North West England, 2004-2016, identifying those who had sustained one or more FF. Site(s) of FF were recorded for each patient, categorised as: ankle, elbow, femur, forearm, humerus, pelvis, ribs, spine, tibia or fibula (recorded as “tibfib”). Cluster analysis was performed on fracture sites, using Jaccard similarity coefficient. Results were plotted on a dendrogram and divided into clusters, as per results derived from elbow and silhouette cluster methods.Results:Out of 28868 patients presenting for BMD estimation, 11003 were identified as having sustained one or more FF. 84.6% patients were female, with overall mean age 67.5years and median T-score -1.12 SD. The most common site of FF was the forearm (n=5045), most commonly co-existing with fractures of the tibia or fibula. Frequencies of the most common and co-existing FF sites are shown in Figure 1 (top). Cluster analysis identified 3 clusters: ankle and elbow; forearm, tibia/fibula, ribs, and spine; pelvis, femur, and humerus. The second half of Figure 1 displays the dendrogram of cluster analysis results, with Jaccard similarity measure.Conclusion:We applied cluster analysis to a large cohort of patients presenting for BMD estimation. Our results are in keeping with previous studies demonstrating the FF to most commonly occur in the forearm, and in those with osteopenia (T-score -2.5 < -1 SD) [2]. To our knowledge, this is the first study to apply cluster analysis to sites of FF. Results may be due to differences in cortical and trabecular bone structure, and have potential to aid prevention, monitoring, and management in at-risk patients.References:[1]National Institute for Health and Care Excellence (NICE). Osteoporosis: assessing the risk of fragility fracture - Clinical Guideline (CG146). 2012;(August):1–14.[2]Siris ES et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004 May 24;164(10):1108–12.Disclosure of Interests:Mrinalini Dey: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen and Novartis.
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HOLI, MALLIKARJUN S., and S. RADHAKRISHNAN. "ESTIMATION OF LOW BONE MASS FOR THE ASSESSMENT OF OSTEOPOROSIS FRACTURE RISK IN INDIAN MEN AND WOMEN USING QUANTITATIVE ULTRASOUND AND DUAL ENERGY X-RAY ABSORPTIOMETRY." Journal of Mechanics in Medicine and Biology 04, no. 01 (March 2004): 47–59. http://dx.doi.org/10.1142/s0219519404000862.
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The objective of the present work is to estimate the prevalence of low bone mass in Indian men and women for the assessment of osteoporosis and fracture risk using quantitative ultrasound and dual energy X-ray absorptiometry (DEXA) and carryout a comparative evaluation for early prediction of osteoporosis. Data collected in this study is analyzed to assess the diagnostic performance of the ultrasound and how its performance compares to DEXA bone mineral density (BMD). Quantitative ultrasound assessment of osteoporosis is carried out by measuring broadband ultrasound attenuation (BUA) and speed of sound (SOS) through calcaneus bone to provide a clinical measure called the stiffness index (SI). The SI is a measure of bone density used to predict the risk of bone fracture due to osteoporosis. Bone mineral density (BMD) measurement is performed in lumbar region (L1–L4) of the spine in anterior-posterior direction using DEXA. In both studies the data is found to be significant in men and women subjects with p<0.0005 and percentage bone loss in men and women are significantly matching in both studies. Ultrasound performance correlates moderately well with DEXA (r=0.60 to 0.68) and provides comparable diagnostic sensitivity to spine BMD in predicting osteoporotic fractures.
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Pérot, Nadia, and Nicolas Bousquet. "Functional Weibull-based models of steel fracture toughness for structural risk analysis: estimation and selection." Reliability Engineering & System Safety 165 (September 2017): 355–67. http://dx.doi.org/10.1016/j.ress.2017.04.024.
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Dey, M., and M. Bukhari. "OP0294 DIFFERENTIAL INFLUENCE OF CO-MORBIDITIES ON SITE OF FRAGILITY FRACTURES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 183.2–183. http://dx.doi.org/10.1136/annrheumdis-2020-eular.855.
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Background:Fragility fractures (FF) can occur at various sites of the skeleton, and are associated with multiple risk factors [1]. The prevalence of FF markedly increases with age. As the longevity of the population increases, so will the incidence of FF, and that of associated co-morbidities and risk factors. There are few data on co-morbidities associated with fractures at each site.Objectives:Identify associations of co-morbidities with sites of FF, by applying cluster analysis.Methods:We reviewed 28868 patients presenting for BMD estimation at a district general hospital in North West England, 2004-2016. We identified patients who had sustained one or more FF at time of presentation. Site(s) of FF were recorded for each patient, including femur, forearm, humerus, pelvis, ribs, spine, tibia or fibula. The following co-morbidities or treatments were recorded: excess alcohol consumption (previous or current); bisphosphonates; coeliac disease; family history of FF; hormone replacement therapy; hyperparathyroidism; hyperthyroidism; inflammatory bowel disease; polymyalgia rheumatica; rheumatoid arthritis; smoking (previous or current); corticosteroids (previous or current). Cluster analysis was performed on fracture sites and co-morbidities, using Jaccard similarity coefficient, and plotted on a dendrogram. Results were divided into an optimal number of clusters, derived using the elbow and silhouette methods.Results:11003 of 28868 patients had sustained one or more FF at time of BMD estimation. Overall, 84.6% patients were female, mean age 67.5years, and median T-score -1.12 SD. Cluster analysis was performed for FF sites and co-morbidities, with Jaccard similarity coefficients calculated. 4 clusters were identified (Figure 1): FF of forearm (n=5054), tibia/fibula (n=2617), spine (n=2352), associated with family history of FF, smoking, corticosteroids, and bisphosphonate treatment; FF of pelvis (n=300) associated with hyperparathyroidism, PMR, coeliac disease, and HRT; FF of femur (n=1181) and humerus (n=1131) associated with IBD and RA; FF of ribs (n=1022) associated with alcohol and hyperthyroidism.Conclusion:Cluster analysis demonstrated 4 distinct subgroups of FF sites and associated co-morbidities. To our knowledge, this is the first study applying cluster analysis to evaluate co-morbidities associated with FF sites. Risk factors may influence trabecular more than cortical bone, accounting for the difference in clusters. Knowledge of risk factors associated with FF site subgroups will aid prophylaxis and management in at-risk patients.References:[1]Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet (London, England). 2002 Jun 1;359(9321):1929–36Disclosure of Interests:Mrinalini Dey: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen and Novartis.
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Kohout, J., G. J. Clapworthy, Y. Zhao, Y. Tao, G. Gonzalez-Garcia, F. Dong, H. Wei, and E. Kohoutová. "Patient-specific fibre-based models of muscle wrapping." Interface Focus 3, no. 2 (April 6, 2013): 20120062. http://dx.doi.org/10.1098/rsfs.2012.0062.
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In many biomechanical problems, the availability of a suitable model for the wrapping of muscles when undergoing movement is essential for the estimation of forces produced on and by the body during motion. This is an important factor in the Osteoporotic Virtual Physiological Human project which is investigating the likelihood of fracture for osteoporotic patients undertaking a variety of movements. The weakening of their skeletons makes them particularly vulnerable to bone fracture caused by excessive loading being placed on the bones, even in simple everyday tasks. This paper provides an overview of a novel volumetric model that describes muscle wrapping around bones and other muscles during movement, and which includes a consideration of how the orientations of the muscle fibres change during the motion. The method can calculate the form of wrapping of a muscle of medium size and visualize the outcome within tenths of seconds on commodity hardware, while conserving muscle volume. This makes the method suitable not only for educational biomedical software, but also for clinical applications used to identify weak muscles that should be strengthened during rehabilitation or to identify bone stresses in order to estimate the risk of fractures.