Rozprawy doktorskie: „Osteoporotic fractures”

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Kaptoge, Stephen Kipkemoi. "Epidemiology of risk factors for osteoporosis and osteoporotic fractures". Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615203.

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Misra, Devyani. "Warfarin use and risk of osteoporotic fractures". Thesis, Boston University, 2012. https://hdl.handle.net/2144/21219.

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Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
OBJECTIVE: Prior studies examining the association of warfarin use and osteoporotic fractures have found conflicting results and have had methodological problems, such as confounding by indication and confounding by duration of warfarin use. Thus, we studied the association of warfarin use with fractures at the hip, spine and wrist, among older men and women with atrial fibrillation recruited from the general population, using rigorous statistical tools to overcome challenges faced by prior studies. METHODS: We included men and women ≥65 years with incident atrial fibrillation, without history of fracture, followed between 2000-2010 from The Health Improvement Network (THIN). Long-term warfarin use was defined in two ways: 1) warfarin use ≥ 1year; 2) warfarin use ≥3 years. Non-use was defined as no use of warfarin over the follow-up period. Propensity scores (PS) for warfarin use were calculated using logistic regression with long-term use of warfarin as the dependent variable and age, sex, body mass index (BMI), history of multiple falls, deep venous thrombosis, pulmonary embolism, heart failure, neuropsychiatric impairment, hyperthyroidism, estrogen use, beta blockers, corticosteroids, bisphosphonates, smoking and alcoholism as independent variables. Each warfarin user was then matched by PS to a non-user by the “greedy matching” method. Incidence rates were calculated for warfarin users and non-users. The association between long-term warfarin use and risk of hip, spine and wrist fractures was evaluated using Cox-proportional hazards models. RESULTS: Incidence rates of hip fracture were 5.21 and 6.20 per 1000 person-years among subjects with warfarin use >1 (n=20,346) and >3 (n=11,238) years, respectively. The hazard ratios of hip fracture for warfarin use >1 and >3 years were 1.08 (95% CI 0.87, 1.35) and 1.13 (95% CI: 0.84, 1.5), respectively. Similar findings were observed between warfarin use and risk of spine or wrist fracture. CONCLUSIONS: Long-term use of warfarin among older adults with atrial fibrillation is not associated with increased risk of osteoporotic fractures and thus, does not necessitate additional surveillance or prophylaxis.
2031-01-01

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Tan, Boon-Kiang. "Non-invasive determinants of osteoporotic fracture risk". University of Western Australia. Centre for Musculoskeletal Studies, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0125.

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[Truncated abstract] The cost of managing osteoporotic fractures places a significant financial burden on the health-care system. To reduce the fracture burden, early identification of fracture risk is essential to allow early intervention. The limitations associated with dual-energy X-ray absorptiometry (DXA), such as limited sensitivity and specificity, cost, ionising radiation and accessibility, have resulted in the emergence of other technologies for assessing bone fragility. An example is the portable and non-ionising quantitative ultrasound (QUS) technology. The discriminatory power of quantitative ultrasonometry in fracture risk identification, either independently or in combination with other established risk factors, currently remains contentious. It is recommended that fracture risk assessment should not only focus on bone status, but also on the risk of falls. Additionally, it has been noted that disability arising from osteoporotic fractures, even when these fractures are not identified clinically, can translate into psychosocial symptoms and a poorer perception of health-related quality of life (HRQoL). The primary aim of the present study was to investigate if a composite model comprising: calcaneal QUS, falls risk and HRQoL assessments, can identify a group of elderly women at high risk of osteoporotic fracture from those at lower risk. One hundred and four community-dwelling women (mean age 71.3 ±5.8 years) were recruited for this study. These women underwent a series of tests that included: DXA bone mineral density (BMD) evaluation of the proximal femur and lumbar spine (L1 L4); calcaneal QUS measurement; spinal radiography; rasterstereographic back surface curvature (BSC) examination; and performance-based assessment of strength, mobility and balance. The women were classified into a `High Risk’group or a `Low Risk’ group using three separate classification criteria: i) low BMD, based on the World Health Organisation (WHO) recommended T-score of < -2.5, and⁄or a history of fragility fracture (Osteoporotic [OP] group versus Non-Osteoporotic [NOP] group); ii) presence of at least one radiographically identified prevalent vertebral fracture (Vertebral Fracture [VF] group versus Non-Vertebral Fracture [NVF] group); or iii) a history of either forearm or wrist fracture (Forearm/Wrist Fracture [WF] group versus Non-Forearm/Wrist Fracture [NWF] group)

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Ridzwan, Mohamad. "A computational orthopaedic biomechanics study of osteoporotic hip fractures". Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/47971.

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Low dual energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) is used as an indicator of reduced bone strength and increased risk of fracture. BMD is widely used to identify patients for fracture prevention treatment. However, many fracture patients are not osteoporotic and would not have been identified by BMD screening. Also, BMD screening vastly overpredicts the number of patients who will progress to fracture. In summary, there is a need to improve explanation and prediction of femoral fracture. The overall aim of this thesis was to develop a finite element (FE) methodology that can explain (better than BMD) femoral fractures. An additional aim was to develop a novel experimental methodology, computed tomography (CT)-based digital volume correlation (CT-DVC). This method measures internal strain and fracture and served as validation for the FE methodology. The study included three groups of femur specimens; Group 1: 15 cadavers served as non-fracture controls, Group 2: 14 patients who had suffered a femoral fracture and Group 3: 13 patients scheduled for arthroplasty due to osteoarthritis served as a second non-fracture control group. The correlation of FE-predicted fracture load with in-vitro testing of cadaveric femurs was superior to that of BMD predictions (R2 = 0.77 and R2 = 0.59). Also, the match between CT-based FE models and the experimental observations was reasonably good (73% match) whereas BMD is unable to explain the fracture type. FE-predicted fracture types matched 13 of 14 patient-specific clinical fractures. Including bone quality and load (fall) direction, FE explained many of the clinical fractures that BMD was unable to explain and critical fall directions were identified. FE predicted lower strength of the fracture group which was associated with smaller sizes of anatomical parameters. Also the CT- DVC method demonstrated consistent results and was deemed to have great potential for a wide range of orthopaedic applications.

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Korpelainen, R. (Raija). "Exercise and risk factors of osteoporotic fractures in elderly women". Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514278054.

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Abstract The aim of this study was to examine lifestyle risk factors for low bone mass, falls and fractures, and to determine the effect of 30-month exercise trial on bone mass, balance, muscle strength and gait in elderly women. Reliability of an inclinometric method for assessing postural sway was evaluated. Data on risk factors, falls and fractures were collected by questionnaires, and calcaneus and radius bone mass were measured from 1,222 women. Lifetime physical activity, low occupational physical activity, type 2 diabetes, hypertension, hormone replacement, thyroid hormone and thiazide use were associated with increased bone mass, while low current physical activity, high coffee intake and late menarche were associated with low bone mass in lean women. Factors associated with fractures were: low lifetime habitual physical activity, diabetes, living alone and calcaneum bone mass. One hundred and sixty women with low femoral neck bone mass were randomly assigned to the exercise group (n = 84) or to the control group (n = 76). The outcomes included radius, proximal femur and calcaneus bone mass, postural sway, muscle strength, gait speed and endurance. Bone mineral density (BMD) at proximal femur decreased in the control group, while no change occurred in the exercise group. Mean trochanter bone mineral content (BMC) decreased more in the control group. The women in the exercise group improved their performance in walking speed and endurance, body sway and leg strength compared to the control group. There were six falls that resulted in fractures in the exercise group and 16 in the control group. The inclinometric method proved to be reliable. In conclusion, lifestyle factors are determinants of bone mass in lean elderly women. Long-term exercise has a site-specific effect on BMC but not on BMD in elderly women. Weight-bearing exercise can modify risk factors for fractures, and may even prevent fall-related fractures in elderly women.

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Hallberg, Inger. "Health-Related Quality of Life in Postmenopausal Women with Osteoporotic Fractures". Doctoral thesis, Linköpings universitet, Omvårdnad, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-51524.

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Background: The global burden of osteoporosis includes considerable numbers of fractures, morbidity, mortality and expenses, due mainly to vertebral, hip and forearm fractures. Underdiagnosis and undertreatment are common. Several studies have shown decreased health-related quality of life (HRQOL) after osteoporotic fracture, but there is a lack of data from long-term follow-up studies, particularly regarding vertebral fractures, which are often overlooked despite patients reporting symptoms. Aim: The overall aim of this thesis was to evaluate the usefulness of a recent low-energy fracture as index event in a case-finding strategy for osteoporosis and to describe and analyse long-term HRQOL in postmenopausal women with osteoporotic fracture. The specific aims were to describe bone mineral density and risk factors in women 55-75 years of age with a recent low-energy fracture (I), estimate the impact of osteoporotic fractures on HRQOL in women three months and two years after a forearm, proximal humerus, vertebral or hip fracture (II), investigate the changes and long-term impact of vertebral or hip fracture on HRQOL in women prospectively between two and seven years after the inclusion fracture (III), and describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis (IV). Design and methods: Data were collected from southern Sweden between 1998 and 2008. A total of 303 women were included in Study I, and this group served as the basis for Studies II (n=303), III (n=67), and IV (n=10). A cross-sectional observational, case-control design (I), and a prospective longitudinal observational design (II-III) were used. In Study IV a qualitative inductive approach with interviews was used and data were analysed using a qualitative conventional content analysis. Results: The type of recent fracture and number of previous fractures are important information for finding the most osteoporotic women in terms of severity (I). Hip and vertebral fractures in particular have a significantly larger impact on HRQOL evaluated using the SF-36 than do humerus and forearm fractures, both during the three months after fracture and two years later, compared between the different fracture groups and the reference population (II). Women who had a vertebral fracture as inclusion fracture had remaining pronounced reduction of HRQOL at seven years. At the mean age of 75.5 years (±4.6 SD), the prevalence of vertebral fracture suggests more negative long-term impact on HRQOL, more severe osteoporosis and a poorer prognosis than a hip fracture does, and this effect may have been underestimated in the past (III). Study IV demonstrates that the women’s HRQOL and daily life have been strongly affected by the long-term impact of the vertebral fracture several years after diagnosis. The women strive to maintain their independence by trying to manage different types of symptoms and consequences in different ways. Conclusions and implications: Type and number of fractures should be taken into account in the case-finding strategy for osteoporosis in postmenopausal women between 55 and 75 years of age. The long-term reduction of HRQOL in postmenopausal women (age span 55-75 yr) with vertebral fracture emerged clearly, compared to women with other types of osteoporotic fractures and references in this thesis. The results ought to be taken into consideration when developing guidelines for more effective fracture prevention and treatment, including non-pharmacological intervention for women with osteoporotic fractures, with highest priority placed on vertebral fractures and multiple fractures, to increase or maintain HRQOL.

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Gao, Xin. "Economic evaluation of three preventive drug therapies for osteoporotic fractures among women at different risk levels". Morgantown, W. Va. : [West Virginia University Libraries], 2001. http://etd.wvu.edu/templates/showETD.cfm?recnum=2045.

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Thesis (Ph. D.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains xi, 211 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 171-186).

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Slavens, Melanie Jean. "Milk Intake in Early and Late Adulthood and Risk of Osteoporotic Hip Fractures in Utah". DigitalCommons@USU, 2006. https://digitalcommons.usu.edu/etd/5532.

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The relationship between milk intake and risk of osteoporotic fractures is uncertain. Associations between milk intake and milk avoidance in relation to osteoporotic hip fracture were examined in the Utah Study of Nutrition and Bone Health (USNBH), a statewide case-control study. Cases were ascertained at Utah hospitals treating 98 percent of hip fractures during 1997-2001 and included 1188 men and women aged 50-89 years. Age- and gender-matched controls were randomly selected from Utah driver's license and Medicare databases (N= 1324). In-person interviews were conducted and participants reported frequency of milk intake per week at age 18 and during pregnancy among women who reported being pregnant. Milk avoidance for a period of more than one year and duration of milk avoidance were also reported. Diet and supplement intake in the one-year period before fracture (cases) or the interview (controls) was assessed using a picture-sort food frequency questionnaire. Milk consumption frequency was categorized into four levels of intake at each life stage. Total calcium intake was categorized into quintiles of distribution of intake. Logistic regression models were used to examine associations between milk intake and milk avoidance and risk of hip fracture while controlling for the potential confounding effects of gender, age, body mass index, alcohol use, smoking, physical activity, estrogen use, and total calorie, protein, calcium, and vitamin D intake. Recent milk intake, milk intake during pregnancy, and milk avoidance duration were not associated with risk of hip fracture. A borderline association was found at age 18 showing a decreased risk of hip fracture among those in the highest quartile (2: 15 cups of milk per week) of milk intake (odds ratio (OR): 0.86, 95 percent confidence interval (Cl): 0.75, 1.00; P = 0.046). Milk avoidance for a year or more was associated with an increased risk of hip fracture compared to those who did not avoid milk (OR: 1.38, 95 percent CI: 1.07, 1.78). A significant interaction was found between milk avoidance and quintile of total calcium intake (P = 0.02). Milk avoidance was associated with a significantly higher risk of hip fracture at the lowest two quintiles of calcium intake (OR: 1.72, 95 percent CI: 1.26, 2.17; P = 0.02 and OR: 1.58, 95 percent CI: 1.01, 2.15; P = 0.01, respectively) but was not associated with elevated risk among those with higher calcium intakes. In conclusion, milk intake during pregnancy for women, and in the year before hip fracture (for cases) or before interview (for controls), was not associated with hip fracture risk. The highest level of milk intake at age 18 was associated with decreased risk of hip fracture. Avoidance of milk for one year or more was associated with hip fracture risk, but only among those with low calcium intake (Q1 and Q2).

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Dodds, R. A. "Structural and metabolic studies on normal and pathological bone". Thesis, Brunel University, 1985. http://bura.brunel.ac.uk/handle/2438/4870.

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Bone is refractory to most conventional biochemical Procedures. However because it is now possible to cut sections (e. g. lopm) of fresh, undemineralized adult bone, this tissue can be analyzed by suitably modified methods of quantitative cytochemistry. A new substrate for assaying hydroxyacyl dehydrogenase activity demonstrated that bone cells may use fatty acids as a major source of energy: detailed analysis of the activities of key enzymes indicated that the paradox of ‘aerobic glycolysis’ of bone could be explained by fatty acid oxidation satisfying the requirements of the Krebs' cycle and directing the conversion of pyruvate to lactate The influence of glucose 6-phosphate dehydrogenase (G6PD) activity in aerobic glycolysis has been considered. The inverse relationships between this activity and that of Na-K-ATPase led to the development of a new method for the latter, based on a new concept in cytochemistry ('hidden-capture' procedure). A major feature of fracture-healing is increased periosteal G6PD activity. The association with the vitamin K cycle has been investigated by feeding rats with dicoumarol which not only inhibited bone-formation but also G6PD activity. The stimulation of this activity in fracture-healing has been linked with ornithine decarboxylase (ODC) activity, for which a new method has been developed. Rats deficient in pyridoxal phosphate (cofactor for ODC) had decreased G6PD responses and also appeared to become osteoporotic. Studies on osteoporotic fractures in the human showed the presence of relatively large apatite crystals close to the fracture-site, and disorganized glycosaminoglycans (demonstrated by the new method of ‘induced birefringence’).

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Bienert, Michaela [Verfasser], Wilhelm [Akademischer Betreuer] Jahnen-Dechent i Sabine [Akademischer Betreuer] Neuß-Stein. "Biologically active bone replacement materials for osteoporotic fractures / Michaela Bienert ; Wilhelm Jahnen-Dechent, Sabine Neuß-Stein". Aachen : Universitätsbibliothek der RWTH Aachen, 2018. http://d-nb.info/1181192919/34.

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Wagner, Helene. "Genetic and Environmental Influences on Bone and Fractures". Doctoral thesis, Uppsala universitet, Ortopedi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-169598.

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Sweden and Norway have the worldwide highest incidence of osteoporotic fractures. As these fractures constitute a tremendous and growing problem, primary prevention is of great importance. The principal causes of an osteoporotic fracture are a fall and a fragile skeleton. The aim of the studies reported in these papers was therefore to determine the genetic and environmental influences on fractures and the genetic influence on the two main reasons to the emergence of osteoporotic fractures; bone mineral density and propensity to fall. In the present thesis, we display that the heritability of fractures is dependent on fracture site and age. With increasing age, lifestyle becomes the dominant explanatory factor. These results indicate that focus should be on lifestyle interventions for the prevention of fractures in the elderly. Although the genetic liability to impaired balance is modest, twins with self-reported impaired balance have a substantially increased risk of osteoporotic fractures compared to their co-twin without impaired balance. Asking a patient about his or her balance might be a simple tool for future risk assessment. The genetic influence on bone phenotypes is under strong genetic influence in Swedish adult twins. These findings are in agreement with the results from previous studies in other countries, with a lower incidence of osteoporotic fractures compared to Sweden. The high heritability of bone phenotypes together with the low heritability of fractures at old age, indicates that bone mineral density has a modest influence on fracture risk at old age. In summary, based on the results in this thesis, more emphasis should be targeted to the prevention of falls, by strength and balance training in order to prevent the occurrence of low energy fractures in the elderly.

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Leach, Martha Ettrusia. "Risk factors for osteoporotic fractures in Black South African men : a case control study / Martha Ettrusia Leach". Thesis, North-West University, 2003. http://hdl.handle.net/10394/272.

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The main focus of bone loss and Osteoporosis (OP) research has been limited almost entirely to women, but OP has become increasingly common in older men and the impact of hip fracture on mortality may actually be greater in men. OP is a major cause of morbidity and mortality in developed countries, at a cost that currently exceeds $10 billion per year in the United States (US) alone. Osteoporotic fractures affect 50 % of women and 20-30% of white men and 4% of black men over the age of 50 years. These statistics may even increase because of increasing life expectancy. Few studies focusing on Blacks have been published to date and very little is known regarding the bone health and the aetiology and prevalence of OP and fractures among older South African blacks. From the above information it is clear that OP is of considerable clinical and economic importance. Without information on the patterns and determinants of bone loss, the formulation of rational prevention and treatment strategies in these groups is not possible. The aim of the study described in this thesis was to investigate the influence of the dietary factors (iron, vitamin C, and protein) and lifestyle factors (alcohol and tobacco smoking) on osteoporotic fractures and bone mineral density in older South African black men using a case-control study design. Sixteen black male patients with fractures of the proximal femur, the proximal humerus or the distal radius and who conformed to the inclusion and exclusion criteria were included in the study. An equal amount of age-matched (K? years), apparently healthy black men with no previous fracture (of the proximal femur and humerus and distal radius), were recruited as a control group. Dual energy X-ray absorptiometry (DEXA) was used for the measurement of the lumbar vertebrae and the proximal femur (hip). Questionnaires were used to gather demographic and medical information, data on physical activity and dietary intakes. Anthropometric measurements and blood samples were taken. Appropriate biochemical analyses were done with standard methods. Both the cases and controls were osteoporotic according to the mean lumbar spine BMD determined in both groups. The BMD was only marginally lower in the cases than in the controls and therefore not statistically significant. The mean tobacco pack years of the cases (13.29) [95% CI: 4.44; 22.141 were almost double that of the controls (7.43) [1.83; 13.031 but it was not statistically significant (p=0.55). Tobacco pack years were negatively associated with BMD of the lumbar spine (p=0.008) even after controlling for possible confounding SUMMARY factors (p=0.001). Malnutrition, as indicated by the low dietary intakes of energy, protein, vitamin C, iron and low BMI, could play a role in the lower bone mineral density (BMD) observed in the cases. The mean protein intakes of the cases (56.1 19) [46.49; 65.741 were very low compared to the recommended 639 per day. This low protein intake was also significantly less compared to the controls (739) [58.28; 88.311. lron intake tended to be lower in the cases compared to the controls (p=0.09). lron intake was not associated with BMD, however, in the stepwise regression analysis; iron intake came out as a possible predictor of BMD of both the lumbar spine and hip, although it was not statistically significant. The BMI was c 19 kg/m2 in 50% of the cases and the controls. S-GGT, a marker of alcohol intake, was significantly increased in the cases with a mean value of 65.88ulL opposed to the 36.33UIL in the control group. S-GGT was the most important predictor of BMD in both the hip and the lumbar spine. There was a significant statistical correlation between lumbar spine BMD (p=0.04); hip BMD (p=0.02) and s-GGT. In conclusion it can be said that malnutrition played a vital role in the low BMD aggravated by the use of tobacco from a young age and alcohol in excessive amounts over weekends. From the results of this study it can be recommended that any intervention programme should focus on alcohol abuse, tobacco smoking and improvement in nutritional status. Children should be encouraged not to smoke and be educated on the detrimental effects of alcohol. It is important to address dietary risk factors associated with OP, namely to increase the overall nutrition of the South African black male with low cost protein and calcium products. Vitamin C enhances iron absorption and may be beneficial for bone collagen. The increased intake thereof by using seasonal fruit can therefore be recommended.
Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2004.

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Chiarello, Eugenio <1981&gt. "Evaluation of the Effectiveness of Femoral Neck Prophylactic Surgery in Elderly Osteoporotic Patiens to Prevent Hip Fractures". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7302/.

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The aim of our RCT was to evaluate safety and efficacy of a new device called Prevention Nail System (PNS) developed for the prevention of femoral neck fractures (FNFs) in patients with severe osteoporosis. The PNS is a titanium screw with a hydroxyapatite coating implanted in the femoral neck in order to reinforce it. We enrolled patients with: FNF; age ≥65 years; DXA of the noninjured hip with a T-score ≤ −2.5 SD. In the fractured hip patients received standard treatment while the contralateral hip was randomized either to receive PNS (group A) or not: control group (B). During each follow-up (FU) at 3, 12 and 24 months, DXA, CT and X-rays of the reinforced hip were performed. The mean age was 83 years and the preoperative DXA was −3.3 SD in both groups. The walking ability of patients with PNS were comparable to controls. The CT scan showed good integration of the PNS in the bone. At the longest available FU 23 patients reported one or more falls. 16 nonfemoral fractures were recorded: 10 (A) and 6 (B) and 6 contralateral hip fractures (CHFs): 3 in the PNS group and 3 in the control group. In A all CHFs occurred within 1 month after surgery and there was a difficult screw placement during surgery, in the control group the CHFs were consequence of a fall (6 months to 2 years after the first FNF). No statistical differences were reported between groups A and B. In conclusion, the device was well tolerated; CHFs in the PNS group should be considered a technical error due to the surgical instruments. Safety of the device can be increased by improving the instruments to reduce the risk of iatrogenic fractures.

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Moayyeri, Alireza. "Risk assessment for osteoporotic fractures among men and women from a prospective population study : the EPIC-Norfolk study". Thesis, University of Cambridge, 2012. https://www.repository.cam.ac.uk/handle/1810/243860.

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Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss >0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.

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Low, Adrian Kah Wai Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "The molecular biology of cancellous bone defects and oestrogen deficiency fractures, in rodents; and the in vivo effects of acid on bone healing". Publisher:University of New South Wales. Clinical School - Prince of Wales Hospital, 2008. http://handle.unsw.edu.au/1959.4/42884.

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The management of significant bone defects, delayed and non-union of fractures can be extremely challenging. Development of specific treatment is hindered by an absence of information regarding the molecular events which regulate these processes. In this thesis, a bilateral cancellous bone defect model of the femur and tibia was developed in a rodent and the spatiotemporal profile of TGF-β, BMP 2 and 7, Smads 1, 4 and 5 characterised. Next, the capability of acid solution to augment healing was tested in both a bone defect and in a closed femoral fracture model. Finally, a long term oestrogen deficiency (OVX) rat model of postmenopausal osteoporosis was characterised and the spatiotemporal profiles of IGF-1, IGFR-1, MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, BMP-2, BMP-4, BMP-7, TGF-β, Smad4, Smad7, VEGF, Flt-1, Ihh and FGF-2 were compared in femoral osteotomies between OVX and Sham groups. The bilateral cancellous defect model was successfully created with a number of advantages with which to recommend its use in future studies. TGF-β, BMP 2 and 7, Smads 1, 4 and 5 had characteristic spatiotemporal profiles during cancellous bone defect healing suggesting that they have a regulatory role. The results of the acid study were inconclusive and problems with substance delivery and maintenance at the desired site need to be addressed in the future to fully test this hypothesis. No significant differences were detected on histology or three-point mechanical testing between the fracture calluses of acid and control groups. In the final study, OVX rats after six months had significantly increased weight and decreased bone mineral density compared to their sham counterparts. A histological delay in osteotomy healing was observed in the OVX group but no significant differences on tensile testing were seen between OVX and Sham groups up to six weeks. Immunohistochemistry revealed that delayed healing may be due to the down-regulation of IGF-1, BMP-2, 4, and 7 and the up-regulation of MMP-3 in OVX compared to Sham groups. In conclusion, the results of this thesis give some insight into the molecular biology of bone defects and osteoporotic fractures. This information may also be useful in the development of specific treatments aimed at augmenting healing in bone defects and osteoporotic fractures.

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Nyandege, Abner. "ASSOCIATION BETWEEN CONCOMITANT USE OF BISPHOSPHONATES AND SEROTONIN REUPTAKE INHIBITORS AND INCREASED RISK OF OSTEOPOROTIC-RELATED FRACTURES: AMONG COMMUNITY-DWELLING POSTMENOPAUSAL WOMEN". VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/557.

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Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs and SSRIs and fracture risk. Separate cross-sectional analyses were performed using data from the 2004-2008 Medical Expenditure Panel Survey (MEPS) and Medicare Part D prescriptions claims data (2008-2010) to examine usage patterns of BPs and SSRIs/SNRIs for women aged ≥45 years and ≥65 years, respectively. For our second objective, a nested-case control was conducted using Medicare claims data (2008-2010). Data from Medicare inpatient claims were linked to Medicare Part D data for all female BP users 65 years or older. We used Cox proportional hazards model to assess the increased risk of osteoporotic-related fractures among propensity score matched (1:1 ratio) cohorts of concomitant users of BPs and SSRIs and BP alone users. Concomitant use of BPs and SSRIs was prevalent and increased with age for each timeframe examined. Findings showed that approximately 12% (using MEPS) and 28% (using Medicare data) of women on BPs were also on SSRIs. For the second objective, 4,214 propensity score matched pairs (average age=80.4 years) of subjects were analyzed. Findings showed that concomitant use of BPs and SSRIs was associated with statistically significant increased risk for any fracture (HR=1.29, 95% CI, 1.07-1.57), but statistically non-significant increased risk for hip (HR=1.16, 95% CI, 0.92-1.47) and vertebral fractures (HR=1.55, 95% CI, 0.97-2.48). Current findings indicate that concomitant use of BPs and SSRIs is not uncommon among postmenopausal women and suggest potential attenuation of antifracture efficacy of BPs by SSRIs. Further studies are needed to understand the clinical impact of concomitant use of these medications among older postmenopausal women.

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Gunnella, Francesca [Verfasser], Raimund W. [Gutachter] Kinne, Michael [Gutachter] Sittinger i Reinhard [Gutachter] Wetzker. "Biotechnologically modified calcium phosphate cement for the stabilization of osteoporotic vertebral compression fractures / Francesca Gunnella ; Gutachter: Raimund K. Kinne, Michael Sittinger, Reinhard Wetzker". Jena : Friedrich-Schiller-Universität Jena, 2019. http://d-nb.info/1206098716/34.

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Martínez, Laguna Daniel. "Efecto de la diabetes mellitus tipo 2 sobre la incidencia de fractura osteoporótica". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457525.

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Objetivos: La diabetes mellitus tipo 2 (DM2) y la osteoporosis son dos procesos prevalentes en las consultas de atención primaria y estrechamente relacionados. Paradójicamente, a pesar de que los pacientes DM2 presentan una mayor masa ósea, presentan un mayor riesgo de fractura. Los objetivos de este estudio es estimar la asociación entre la presencia de DM2 incidente y la incidencia de fractura osteoporótica en población española, y secundariamente analizar la relación entre DM2 y la mortalidad en los primeros años tras la aparición de una fractura osteoporótica. Método: Estudio de cohortes de base poblacional. Para el sub-estudio 1 se seleccionaron los pacientes con DM2 incidente entre 2006-1013 de la base de datos SIDIAP y se emparejaron con 2 pacientes no diabéticos. Para el sub-estudio 2 se seleccionaron pacientes ≥50 años con DM2 entre 2006-2013 y se emparejaron con 2 sujetos no diabéticos. Se recogió información sobre factores de riesgo, fracturas incidentes, mortalidad y factores confusores. Mediante modelos de supervivencia de Fine and Gray se analizó la asociación entre DM2 y riesgo de fractura de cadera. Para el sub-estudio 2 se calcularon tasas de mortalidad post-fractura y mediante modelos de regresión de Cox ajustados se calculó el riesgo de mortalidad según la presencia o no de DM2. Resultados: Se identificaron 58.483 pacientes con DM2 incidente y 113.448 pacientes no diabéticos, seguidos durante una mediana (rango inter-cuartil) de 2,63 (2,93) años. En los primeros años (hasta 6 años) después de la aparición de la enfermedad, 444/58.483 (0,8%) pacientes con DM2 sufrieron una fractura femoral vs 776/113.448 (0,7%) en los pacientes no diabéticos. El SHR ajustado fue de 1,20 [IC 95% 1,06 - 1,35]. En sub-estudio 2 s e identificaron un total de 166.106 pacientes DM2 y 332.212 no diabéticos, de los cuales 11.066 (6,66%) DM2 y 21.564 (6.49%) no diabéticos sufrieron una fractura, y éstos se incluyeron para el análisis principal. La tasa de mortalidad post-fractura fue 53,93 por 1.000 personas/año. Más de la mitad de las muertes observadas ocurrieron durante los primeros dos años después de una fractura, con una mayor proporción en el primer año después de una fractura femoral. El HR ajustado de mortalidad post-fractura fue de 1,30 [IC 95% 1,23-1,37]. Conclusiones: Los pacientes recientemente diagnosticados de DM2 presentan un aumento del 20% del riesgo de fractura de cadera en comparación a los no diabéticos, ya incluso en los primeros años de evolución de la enfermedad. Los pacientes DM2 presentan entre un aumento 20-30% de riesgo muerte por cualquier causa tras una fractura, observando una mayor tasa de mortalidad tras una fractura femoral.
Aims: Type 2 diabetes mellitus (T2DM) and osteoporosis are two highly prevalent long-term comorbidities. Paradoxically, although T2DM patients have a higher bone mass, they present an increased risk of fracture. The objectives of this study are to estimate the association between the presence of T2DM and the incidence of osteoporotic fracture in the Spanish population and secondarily to analyze the relationship between T2DM and all-cause mortality after an osteoporotic fracture. Methods: Population-based cohort study. For sub-study 1, patients with incidentT2DM between 2006-1013 from the SIDIAP database were selected and matched with 2 non-diabetic patients. For sub-study 2 T2DM patients ≥50 years between 2006-2013 were selected and were matched with 2 non-diabetic subjects. Information about risk factors, incident fractures, mortality and confounding factors were collected. Survival models of Fine and Gray were fitted to model the association between T2DM and hip fracture risk. Post-fracture mortality rates were calculated for sub-study 2 and Cox regression models were fitted to calculate mortality risk according to T2DM status. Results: 58,483 patients with incident T2DM and 113,448 non-diabetic patients were selected, followed by a median (interquartile range) of 2.63 (2.93) years. In the early years (up to 6) following disease onset, 444/58,483 (0.8%) T2DM patients sustained a hip fracture, compared to 776/113,448 (0.7%) matched non-diabetic controls. The adjusted SHR was 1.20 [95% CI 1.06 - 1.35]. In sub-study 2, a total of 166,106 T2DM and 332,212 non-diabetic patients were identified, of whom 11,066 (6.66%) T2DM and 21.564 (6.49%) non-diabetic patients sustained a fracture, and were then included for the main analysis Mortality rate post-fracture was 53.93 per 1,000 person-years. More than 50% of the observed deaths occurred during the first two years after a fracture, with the higher proportion of them seen in the first year following a hip fracture. The adjusted HR mortality post-fracture was 1.30 [95% CI 1.23-1.37]. Conclusions: Recently diagnosed T2DM patients have a 20% higher risk of hip fractures in the first few years following disease onset, compared to non-diabetic patients. T2DM patients have a 20-30% excess all-cause mortality following a fracture, with a higher mortality rate after a femoral fracture.

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Sousa, Cristina de Jesus. "An?lise do risco de fraturas ?sseas nas mulheres idosas por meio da ferramenta FRAX". Universidade Cat?lica de Bras?lia, 2018. https://bdtd.ucb.br:8443/jspui/handle/tede/2498.

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This is a quantitative, cross-sectional and descriptive study whose general objective was to evaluate the bone quality of elderly women with more than 60 years of age attending a general gynecology clinic in the Distrito Federal, through the application of the FRAX Tool. The study site was a private general gynecological clinic and the sample consisted of 147 were elderly women (60 to 90 years). For the data collection, three instruments were used: a sociodemographic questionnaire, the FRAX tool and the FRAQ-Brazil instrument. Comparisons of proportions between two independent groups were performed using Fisher's exact test. Categorical variables were described with counts and proportions. Quantitative variables of normal and asymmetric distribution were described as mean ? standard deviation and median (interquartile range) respectively. Normality was assessed by visual inspection of histograms. The R software was used in the statistical analysis of data. All probabilities of significance are bilateral and values less than 0.05 are considered statistically significant. The results obtained are found in articles 1 and 2. The research allowed an intense literature review to contribute to an understanding of which factors limit the use of the FRAX Tool, and which groups of older people should be better and more carefully analyzed for orientation. We found a mean and high risk of osteoporotic fractures assessed by applying the FRAX tool in non-elderly patients by 0.3%, in elderly patients up to 79 years old was found in 3,7% and in 45,5% of the elderly women above of 80 years. It can be concluded that the FRAX tool, despite some limitations, is important for the early identification and screening of individuals at risk of fractures due to its simplicity of application, allowing early and safe therapeutic decision making. It was also concluded that there is a significant increase in the risk of osteoporotic fractures with advancing age.
Trata-se de um estudo quantitativo, transversal e descritivo cujo objetivo geral foi avaliar a qualidade da massa ?ssea de idosas com mais de 60 anos frequentadoras de uma cl?nica de ginecologia geral no Distrito Federal, por meio da aplica??o da Ferramenta FRAX. O local do estudo foi uma cl?nica particular de ginecol?gica geral e a amostra foi constitu?da 147 mulheres idosas (60 a 90 anos). Para a coleta de dados, utilizaram-se tr?s instrumentos: um question?rio sociodemogr?fico, a Ferramenta FRAX e o instrumento FRAQ-Brasil. Compara??es de propor??es entre dois grupos independentes foram efetuadas utilizando-se teste exato de Fisher. Vari?veis categ?ricas foram descritas com contagens e propor??es. Vari?veis quantitativas de distribui??o normal e assim?trica foram descritas como m?dia ? desvio padr?o e mediana (intervalo interquartil) respectivamente. Normalidade foi avaliada com a inspe??o visual de histogramas. O software R foi utilizado na an?lise estat?stica de dados. Todas as probabilidades de signific?ncia apresentadas s?o do tipo bilateral e valores menores que 0.05 considerados estatisticamente significantes. Os resultados obtidos encontram-se nos artigos 1 e 2. A pesquisa permitiu a realiza??o de uma intensa revis?o de literatura visando contribuir para uma compreens?o de quais fatores limitam o uso da Ferramenta FRAX, e quais grupos de idosos devem ser melhores e mais cuidadosamente analisados para a orienta??o. Encontrou-se m?dio e alto risco de fraturas osteopor?ticas avaliado atrav?s da aplica??o da Ferramenta FRAX nas pacientes idosas aos 79 anos o percentual encontrado foi de 3,7% e em 45,5% nas idosas acima dos 80 anos. Pode-se concluir que a Ferramenta FRAX, apesar de algumas limita??es, ? importante para a identifica??o precoce e o rastreamento de indiv?duos com risco de fraturas, devido ? sua simplicidade de aplica??o, permitindo uma tomada de decis?o terap?utica precoce e segura. Concluiuse tamb?m que h? um aumento importante do risco de fraturas osteopor?ticas com o avan?ar da idade.

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Braz, Manuela Giuliani Marcondes Rocha. "Sequenciamento paralelo em larga escala de genes candidatos para fragilidade óssea em indivíduos com osteoporose grave, familiar ou idiopática". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-22102018-123623/.

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A osteoporose é uma doença de alta prevalência na população geral, e a ocorrência de fraturas se associa a grande morbi-mortalidade e impacto econômico. Na maioria dos indivíduos afetados, a osteoporose tem etiologia multifatorial, com herdabilidade estimada entre 50 e 85%, atribuível a um conjunto de variantes genéticas de pequeno efeito individual. Raramente, há casos de osteoporose associada a síndromes monogênicas, decorrentes de defeitos genéticos de grande impacto. Postula-se que indivíduos com quadros extremos de osteoporose não sindrômica possam ter causa genética mono- ou oligogênica, atribuível a variantes de impacto intermediário sobre o fenótipo, ainda pouco reconhecidas. Nos últimos anos, o avanço das tecnologias de sequenciamento permitiu o reconhecimento de novos genes associados à fragilidade óssea e atualmente possibilita a análise simultânea de múltiplos genes. Neste contexto, os objetivos deste projeto de pesquisa foram: 1) buscar genes candidatos para fragilidade óssea previamente associados a doenças Mendelianas com alto impacto na resistência óssea, fenótipos extremos de osteoporose e estudos de associação genética em escala genômica (GWAS) para osteoporose; e 2) pesquisar a presença de variantes alélicas patogênicas nestes genes candidatos em indivíduos com osteoporose grave, familiar ou idiopática. A partir de revisão sistemática, 128 genes candidatos foram selecionados para compor um painel de sequenciamento paralelo em larga escala. O sequenciamento incluiu todos os éxons e 25 pares de bases das junções íntron-éxon. Foram consideradas variantes genéticas de interesse aquelas raras (frequência alélica < 1%) e com predição de alto impacto sobre a proteína codificada. Trinta e sete indivíduos (7 famílias e 21 casos isolados) foram selecionados seguindo critérios clínicos, laboratoriais e densitométricos restritivos, excluindo-se pacientes com causas secundárias de osteoporose. A coorte foi composta por homens em 54%, a mediana de idade ao diagnóstico foi 44 anos e 86% tinham histórico de fratura. Dentre os 28 casos índices, foram identificadas 33 variantes de interesse. Após análise de segregação familiar, foi possível excluir patogenicidade de cinco destas variantes, restando 28 variantes potencialmente patogênicas, presentes em 71% da coorte. Todas as variantes foram encontradas em heterozigose, sendo 26 variantes de ponto não-sinônimas, uma deleção de 9 pares de bases, e uma grande deleção envolvendo o único éxon codificador do gene candidato GPR68. Foi encontrada uma associação de variantes em genes diferentes em 21% da coorte, incluindo uma mulher jovem com osteoporose grave e variantes em WNT1, PLS3 e NOTCH2. A análise de segregação familiar neste caso sugeriu um efeito patogênico aditivo das variantes. Vinte e cinco porcento das variantes potencialmente patogênicas foram identificadas em genes candidatos bem estabelecidos (WNT1, PLS3, COL1A1, COL1A2), e 57% se localizam em novos genes candidatos identificados inicialmente por GWAS, como NBR1 e GPR68, também associados à alteração da remodelação óssea em modelos animais. Os resultados deste trabalho dão relevância a novos genes na fisiologia da resistência óssea e indicam um papel proeminente de interações digênicas/oligogênicas em casos de osteoporose grave, familiar ou idiopática. O reconhecimento de novas vias associadas à fragilidade óssea pode levar ao desenvolvimento de novos tratamentos, e a identificação de variantes patogênicas associadas à osteoporose pode, futuramente, permitir um manejo clínico personalizado de pacientes e seus familiares
Osteoporosis is a highly prevalent disorder resulting in fragility fractures and incurring in great morbi-mortality and economic burden. In most cases, osteoporosis has a multifactorial etiology, with an estimated heritability of 50-85% attributable to a combination of several low-impact genetic variants. Rarely, cases of syndromic osteoporosis due to high-impact genetic defects are seen. It is therefore hypothesized that severe/idiopathic cases of otherwise inconspicuous osteoporosis may have a monoor oligogenic etiology due to genetic variants with an intermediate effect. During the past years, advances in molecular sequencing have revealed novel candidate genes for bone fragility, and have enabled simultaneous sequencing of multiple genes. In this context, the objectives of this research project were: 1) to identify candidate genes for bone fragility, as previously reported in association to Mendelian disorders with high impact on bone resistance, idiopathic or familial osteoporosis, and genome-wide association studies (GWAS) for bone mineral density and fragility fractures; and 2) to perform molecular analysis of these candidate genes in patients with severe, familial or idiopathic osteoporosis. Through a systematic review, 128 candidate genes were identified and included in a panel for massively parallel sequencing. Coding regions and 25-bp boundaries were captured and sequenced. Rare variants (allele frequency < 1%), with a predicted high impact on protein function were initially selected as variants of interest. Thirty-seven subjects (21 sporadic cases and 7 families) were included according to stringent criteria based on clinical and densitometric evaluation, excluding individuals with secondary osteoporosis. Males represented 54% of the cohort, median age at diagnosis was 44 years, and 84% of subjects had a history of fractures. Thirtythree variants of interest were identified initially. After familial segregation analysis, 5 variants were considered as benign in regard to bone fragility, resulting in 28 potentially pathogenic variants, all heterozygous, present in 71% of the cohort. Of these variants, 26 were nonsynonymous, there was one 9-bp deletion and one large deletion involving the only coding exon of candidate gene GPR68. An association of two or more variants in different genes was present in 21% of the cohort, including a young woman with severe osteoporosis and variants in WNT1, PLS3 and NOTCH2. Familial segregation in this case suggested an additive pathogenic effect of these variants. Twenty-five percent of potentially pathogenic variants were identified in well-established candidate genes (WNT1, PLS3, COL1A1, COL1A2), and 57% located to novel candidate genes initially identified by GWAS, such as NBR1 and GPR68, which have been previously associated to changes in bone remodeling in mouse models. These results support the involvement of GWAS genes in the pathophysyiology of osteoporosis, and indicate a prominent role for digenic/oligogenic interactions in cases of severe, familial or idiopathic osteoporosis. Recognition of new molecular pathways in the determination of bone fragility may lead to the development of new drugs, and the identification of pathogenic variants associated to osteoporosis may allow individualized clinical management of patients and their relatives

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Bastos-Silva, Yasmin 1990. "Correlação do risco de fratura osteoporótica em 10 anos calculado pelo FRAX com e sem densitometria em mulheres brasileiras na pós menopausa = Correlation between osteoporotic fracture risk in 10 years calculated by FRAX with and without bone densitometry in post menopause brazilian women". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312826.

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Orientador: Lúcia Helena Simões da Costa Paiva
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O risco de fratura osteoporótica pode ser avaliado clinicamente baseado em fatores clínicos e pela densidade mineral óssea (DMO), entretanto esses parâmetros não são bons preditores do risco de fratura. Recentemente, o Brasil foi incluído no instrumento fracture risk assessment tool- FRAX-BRASIL, porém seu uso tem sido limitado na prática clínica. OBJETIVO: Avaliar o grau de concordância entre o risco de fratura em 10 anos calculado pelo FRAX-BRASIL com e sem densitometria em mulheres brasileiras na pós-menopausa. MÉTODO: Realizou-se um estudo de corte transversal no período de novembro de 2014 a fevereiro de 2015, com 402 mulheres em acompanhamento no Ambulatório de Menopausa do Hospital da Mulher Prof. Dr. José Aristodemo Pinotti em Campinas-SP. Foram incluídas mulheres com 40 anos ou mais, em amenorreia há pelo menos 12 meses e com exame de densitometria óssea prévio a qualquer tratamento medicamentoso para osteopenia ou osteoporose. As mulheres foram entrevistadas por um pesquisador durante a consulta de rotina, na qual foram coletadas informações sobre fatores de risco necessários para o questionário FRAX-BRASIL e dados da densitometria óssea. Os dados obtidos foram inseridos na plataforma online FRAX-BRASIL, em que foi calculado o risco para uma fratura maior e de quadril, utilizando-se somente os fatores de risco clínicos e o risco incluindo valores de DMO do colo do fêmur em g/cm2. ANÁLISE ESTATÍSTICA: Para análise do grau de concordância entre os riscos de fraturas com e sem densitometria óssea foi utilizado o coeficiente de correlação intraclasse (ICC). O Teste de Mann-whitney foi utilizado para comparação entre as médias do risco de fratura calculado com e sem DMO; para comparação entre as frequências de alto risco calculadas com e sem DMO foi utilizado o Teste de comparação entre duas proporções. Para análise da associação entre as variáveis clinico/demográficas e a variação do risco de fratura foi utilizada a análise de regressão linear. O nível de significância adotado foi <0,05. RESULTADOS: A probabilidade de fratura em 10 anos calculada pelo FRAX-BRASIL para fratura de quadril e para fratura maior somente pelos fatores de risco clínicos foi de 0,84% ±1,92 e 4,03% ±2,98 e com DMO foi de 0,83% ±1,76 e 4,05% ±2,98 respectivamente. O coeficiente de correlação intraclasse entre o FRAX-BRASIL com e sem DMO foi de 0,76 (IC95% 0,716-0,799) para uma fratura maior e de 0,644 (IC95% 0,583-0,698) para fratura de quadril. Ao avaliar as mulheres utilizando o FRAX com DMO 0,75% e 5,22% excederam os limiares de alto risco para fratura maior e de quadril, respectivamente. Sem o acréscimo da densidade óssea 1% e 11,44% apresentaram alto risco para fratura maior e de quadril, respectivamente. Dessa forma a recomendação de tratamento foi concordante entre o FRAX com e sem DMO em 99,75% dos casos de alto risco de fratura maior e de 93,78% para o quadril. Os fatores associados a menor variação FRAX com e sem foram maior idade, menor DMO, menor T-score e ausência de fratura previa tanto para fratura maior como para quadril. O menor IMC esteve associado a menor variação do FRAX apenas para fratura maior. CONCLUSÃO: O risco de fratura maior ou de quadril foi baixo na população estudada. O FRAX-BRASIL apresentou alta concordância para estimar o risco de fratura maior e concordância moderada para fratura de quadril apresentando uma estimativa de risco para fratura semelhante com ou sem DMO em nossa população
Abstract: The risk of osteoporotic fracture can be clinically evaluated based on clinical factors and by the bone mineral density (BMD), but these parameters are not good predictors of fracture risk. Recently, Brazil was included in the fracture risk assessment tool- FRAX-BRAZIL, but its use has been limited in clinical practice. GOAL: To evaluate the degree of correlation between the degree of correlation between the risk of fracture in 10 years calculated by FRAX-BRAZIL with and without densitometry in Brazilian postmenopausal women. METHODS: A cross-sectional study was conducted with 402 women followed up at the Menopause Ambulatory at the Women's Hospital Prof. Dr. José Aristodemo Pinotti in Campinas-SP. Women were included with 40 years or more in amenorrhea for at least 12 months and with bone densitometry exam prior to any drug treatment for osteopenia or osteoporosis. A researcher interviewed the women during a routine visit, where information about risk factors necessary for the FRAX-BRAZIL questionnaire and data of bone densitometry were collected. The collected data were inserted on the online platform FRAX-BRAZIL where the risk for major fractures and of the hip using only clinical risk factors and the risk including femoral neck BMD values in g / cm2. STATISTICAL ANALYSIS: To analyze the degree of correlation between the risk of fractures with and without bone densitometry was used the intraclass correlation coefficient (ICC). The Mann-Whitney test was used to compare the averages of fracture risk calculated with and without BMD; to compare the frequencies of high risk calculated with and without BMD was used the compare Test between two proportions. For analysis of the association between clinical / demographic variables and the change of the fracture risk was used linear regression analysis. The significance level was <0.05. RESULTS: The fracture probability calculated in 10 years by using the FRAX-BRAZIL for hip fracture and major fracture only by clinical risk factors was 0.84% ± 1.92 and 4.03 ± 2.98% and BMD was 0.83% ± 1.76 and 4.05 ± 2.98%, respectively. The intraclass correlation coefficient between the FRAX-BRAZIL with and without BMD was 0.76 (IC95% 0.716-0.799) for a major fracture and 0.644 (IC95% 0.583-0.698) for hip fracture. When evaluating women using FRAX with BMD 0.75% and 5.22% exceeded the high-risk thresholds for major and hip fracture, respectively. Without the increase of the bone density 1% and 11.44% presented high risk for major fractures and of hip, respectively. Then the treatment recommendation was consistent between the FRAX with and without BMD in 99.75% of cases of high risk of major fracture and 93.78% for the hip. Factors associated with less variation FRAX with and without were older, lower BMD, lower T-score, and no previous fracture both for major fracture as to hip fracture. The BMI was associated with lower variation in the FRAX only to major fracture. CONCLUSION: The risk of major fracture or of the hip was low in the study population. The FRAX-BRAZIL presented a high correlation to estimate the risk of major fractures and moderate agreement for hip fracture presenting a risk estimate for similar fracture with or without BMD in our population. The FRAX-BRAZIL presented a high correlation to estimate the risk of major fractures and moderate correlation for hip fracture presenting a risk estimate for similar fracture with or without BMD in our population
Mestrado
Fisiopatologia Ginecológica
Mestra em Ciências da Saúde

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Stefani, Kelly Cristina. "Relação do polimorfismo do receptor P2X7 com a densidade mineral óssea: estudo em pacientes idosos com fraturas do tornozelo". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-28022019-100221/.

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O objetivo deste estudo foi determinar se a variação genética no gene do receptor P2X7 está associada com a diminuição da densidade mineral óssea e o risco de osteoporose em pacientes acima de 50 anos de idade com fratura de tornozelo. Foi realizado um estudo diagnóstico Nível I. Os pacientes acima de 50 anos com fratura de tornozelo submetidos ao tratamento cirúrgico foram divididos em dois grupos após o resultado da densitometria óssea: o grupo de estudo com osteopenia (T score entre -1 e -2,5) ou osteoporose (T score <= -2,5) e o grupo controle com valores de normalidade (com T score >= -1). Os critérios de exclusão foram alterações que levam à osteoporose secundária. Os pacientes foram genotipados para 15 polimorfismos de nucleotídeo único (SNPs) não sinônimos dentro do receptor P2X7 (numerados de 1 à 15) obtidos a partir da saliva. Avaliamos 121 pacientes com fratura de tornozelo, sendo 56 do grupo controle e 65 do grupo de estudo. Todos os pacientes eram sedentários, não utilizavam nenhum medicamento para tratamento de osteoporose, não eram tabagistas e sofreram trauma de baixa energia. A análise agrupada das alterações dos SNPs demonstrou que se o gene tem 3 ou mais variantes de SNPs (36,4% dos 121 pacientes), dos 15 possíveis, ele está alterado com repercussão clínica relacionada à perda ou ganho de função do gene. E ao analisar as alterações dos SNPs, individualmente, os resultados sugerem que: os SNPs 1,4,14 e 15 são variantes de perda de função; SNPs 5 e 10 são descritos como variantes de perda de função; entretanto, não têm influência na nossa população; SNPs 11 e 13 são variantes de perda de função e não ganho de função, como descrito na literatura; e SNP 12 foi associado à perda de função em nossa população. Podemos ressaltar como limitações do nosso estudo o fato de nos concentramos principalmente em polimorfismos não sinônimos que não cobrem toda a variação genética em P2X7 e no número pequeno de participantes quando comparados com a literatura mundial. Em contrapartida, um dos pontos fortes do nosso estudo é ser o primeiro a avaliar o P2X7 na população brasileira, que é bastante heterogênea do ponto de vista genético devido à nossa miscigenação, quando comparado com os outros estudos que avaliaram a população do norte da Europa, que é mais homogênea geneticamente. Em conclusão, o polimorfismo do SNP 12 em P2X7 está associado à densidade mineral óssea e risco de fraturas de tornozelo
The purpose of this study was to determine whether a genetic variation in the P2X7 receptor gene is associated with reduced bone mineral density and the risk of osteoporosis in patients over 50 years of age with ankle fractures. A Level-1 diagnostic study was conducted. Patients over 50 years of age with ankle fractures who had undergone surgical treatment were divided into two groups following the result of a bone densitometry: a study group with osteopenia (bone mineral density T score between -1 and -2.5) or osteoporosis (bone mineral density T score <= -2.5) and the control group with normal values (bone mineral density T score >= -1). Exclusion criteria were alterations that led to secondary osteoporosis. Patients were genotyped for 15 nonsynonymous single nucleotide polymorphisms (SNPs) within the P2X7 receptor (numbered from 1 to 15) obtained from saliva. We evaluated 121 patients with ankle fractures, 56 being from the control group, and 65 from the study group. All patients were sedentary, did not take any medication for the treatment of osteoporosis, did not smoke, and had suffered a low-impact trauma. The grouped assessment of the SNP alterations showed that if a gene has three or more SNP variants (36.4% of the 121 patients), out of the 15 possibilities, it is altered with clinical repercussions related to the loss or gain of the function of the gene. In evaluating the SNP alterations individually, the results suggest that: SNPs 1,4,14, and 15 are loss of function variants; SNPs 5 and 10 are described as loss of function variants; however, they have no influence on our study population; SNPs 11 and 13 are loss of function variants and not gain of function function as is described in the literature; and SNP 12 was associated with a loss of function in our population. In conclusion, we showed that the functional polymorphisms in P2X7 are associated with Bone Mineral Density and the risk of ankle fractures. As limitations to our study, we can point out the fact that we focused mainly on nonsynonymous polymorphisms, which do not cover all the genetic variations in P2X7, and the small number of participants when compared to the world literature. On the other hand, a strength of our study is that it was the first to assess P2X7 in the Brazilian population, which is quite heterogeneous from the genetic point of view due to our miscegenation, as compared to other studies that evaluated the population of northern Europe, which is genetically more homogeneous. In conclusion, the SNP12 polymorphism in P2X7 is associated with Bone Mineral Density and the risk of ankle fractures

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Ferreira, Neville de Oliveira 1982. "Prevalência de fratura vertebral, alterações radiológicas, dor nas costas, qualidade de vida em mulheres com osteoporose pós-menopausa e validação da versão na língua portuguesa do questionário de qualidade de vida QUALEFFO-41". [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308725.

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Orientador: Lúcia Helena Simões da Costa-Paiva
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-18T22:13:15Z (GMT). No. of bitstreams: 1 Ferreira_NevilledeOliveira_D.pdf: 2260205 bytes, checksum: 4735926d615eaa3b10d11ae68acd6940 (MD5) Previous issue date: 2011
Resumo: Objetivo: Avaliar a prevalência de fratura vertebral, alterações radiológicas, dor nas costas, e associação com qualidade de vida em mulheres com osteoporose pós-menopausa e validar a versão na língua portuguesa do questionário de qualidade de vida QUALEFFO-41 em mulheres brasileiras com fratura vertebral. Métodos: Este estudo coletou dados de 126 mulheres com osteoporose e 43 mulheres sem osteoporose. O estudo de prevalência de fratura vertebral (FV), osteófitos e dor nas costas, foi um corte transversal com o total de 126 mulheres com osteoporose lombar pós-menopausa diagnosticada pela densitometria óssea selecionadas no Ambulatório de Menopausa do CAISM. As mulheres responderam entrevista sobre dados sociodemográficos e clínicos, e o questionário QUALEFFO-41. Todas realizaram radiografia de coluna para pesquisa de alterações radiológicas. Para a análise estatística utilizou-se os testes de Mann-Whitney ou T de Student, testes exato de Fisher ou qui-quadrado e regressão múltipla. O estudo de validação do QUALEFFO-41 foi realizado apenas com 43 com FV por osteoporose (grupo fratura) e 43 sem osteoporose (grupo controle), pareadas por idade (±3 anos). Foram aplicados o QUALEFFO-41 e o SF-36 (comparação teste-reteste). Calculou-se o coeficiente ? de Cronbach, coeficiente de Correlação Intraclasse, coeficiente Kappa (k), Odds ratio e curva ROC. Resultados: Os resultados foram apresentados em três artigos. No primeiro artigo, a prevalência de FV nas 126 mulheres foi de 34,1% e o tipo de FV mais prevalente foi a triangular anterior (45,9%). Não houve diferença na qualidade de vida (QV) entre as mulheres com osteoporose com e sem FV, porém o maior número de fraturas associou-se a pior QV. Os fatores associados à pior QV foram cor da pele não branca, obesidade, ausência de trabalho remunerado, sedentarismo, baixa escolaridade e não uso de medicação para osteoporose. No segundo artigo sobre prevalência de alterações radiológicas e dor nas costas, a prevalência de FV foi de 34,1 % e de osteófitos de 92,1%. A prevalência de dor nas costas foi de 66,7% e observou-se associação entre a dor nas costas com a presença de osteófitos (p=0,0157) e pior QV. No terceiro artigo de validação do QUALEFFO-41, o coeficiente ? de Cronbach dos domínios variou entre 0,74 e 0,84; o ICC dos domínios variou entre 0,67 e 0,90; a maioria das questões apresentou um coeficiente k maior do que 0,50 e demonstrou boa validade convergente e discriminante. As mulheres do grupo FV apresentaram comprometimento na QV em ambos os questionários (p<0,05) e houve boa correlação entre os domínios do QUALEFFO-41 e os seus correspondentes do SF-36, exceto para Função Social. A avaliação pela curva ROC e regressão logística demonstrou que todos os domínios do QUALEFFO-41 foram significativamente preditivos de FV. Conclusão: A prevalência de FV por osteoporose foi alta, com comprometimento na QV independente da FV. Também houve uma alta prevalência de dor nas costas associada à presença de osteófitos e pior QV. O QUALEFFO-41 na língua portuguesa pode ser utilizado em mulheres brasileiras com FV por osteoporose, pois mostrou ter boas características psicométricas, demonstrando comprometimento na QV e boa capacidade de discriminar a QV em mulheres com FV
Abstract: Objective: To evaluate the prevalence of vertebral fractures, radiographic abnormalities, back pain, and association with quality of life in women with postmenopausal osteoporosis, and to validate the Portuguese version of the quality of life QUALEFFO-41 questionnaire in Brazilian women with osteoporosis vertebral fractures. Methods: This study was conducted with a total of 126 women with osteoporosis and 43 women without osteoporosis. The study of the prevalence of vertebral fractures (VF), osteophytes and back pain, was a cross sectional study with a total of 126 postmenopausal women, with lumbar osteoporosis diagnosed by bone densitometry, selected from the Menopause Outpatient Clinic of the Women's Integrated Healthcare Center (CAISM). The women were interviewed about sociodemographic/clinical data and the QUALEFFO-41 questionnaire. Lumbar spine radiograph was performed in all participants to study radiographic abnormalities. The statistical analysis was performed by the Mann-Whitney or Student's T-test, Fisher's Exact or Chi-square, and multiple regression. The QUALEFFO-41 validation study was conducted with only 43 women with osteoporosis VF (fracture group) and 43 women without osteoporosis (control group), age-matched (±3 years). The QUALEFFO-41 questionnaire was administered twice in four weeks and compared to SF-36 (testretest). For analysis were calculated the Cronbach's ? Coefficient, the Intraclass Correlation Coefficient, the Kappa's Coefficient, Odds ratio and ROC curve. Results: The results were presented in three articles. In the first, the prevalence of VF in the 126 women was 34,1% and the most prevalent type of VF was anterior wedge (45.9%). No difference was observed in the quality of life (QOL) between women with osteoporosis with and without VF, although there was direct correlation between number of VF and worse QOL. Factors associated with worse QOL were non-white skin color, obesity, no paid job, sedentary lifestyle, low level of school education and non-use of osteoporosis drugs. In the second article about prevalence of radiographic abnormalities and back pain, the prevalence of VF was 34,1 % and of 92,1% to osteophytes. Back pain in the last four weeks was prevalent in 66.7% of women and it was observed a association between back pain with osteophytes presence (p=0,0157) and worse QOL. In the third article of validation of QUALEFFO-41, the Cronbach's ? coefficient of the domains ranged between 0,74 and 0,84; the ICC of the domains ranged between 0,67 and 0,90; the majority of questions showed a k coefficient higher than 0,50 and demonstrated good convergent validity and discriminant validity. The group of women with VF showed impairment in the QOL in both questionnaires (p<0,05) and there was a good correlation among the QUALEFFO-41 domains and their corresponding SF- 36 domains, except for Social Function. All QUALEFFO-41 domains were significantly predictive of VF on assessment of the ROC curve. Conclusion: The prevalence of osteoporosis VF was high, with impairment of the QOL independent of VF. There is also a high prevalence of back pain associated with osteophytes and worse QOL. The Portuguese version of the QUALEFFO-41 may be used in Brazilian women with osteoporosis VF because it shows good psychometric characteristics, the impairment of the QOL and good ability to discriminate QOL in women with osteoporosis VF
Doutorado
Fisiopatologia Ginecológica
Doutor em Ciências da Saúde

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Hillier, Sharon Lee. "Water fluoridation and osteoporotic hip fracture". Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264665.

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Ugarte, Corbalán Laura de 1988. "The regulatory roles of MicroRNAs in bone remodeling and osteoporosis". Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/565403.

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In bone field, microRNAs (miRNAs) have been described as key factors regulating bone formation, remodeling, and homeostasis. The identification of miRNAs involved in skeletal function will be essential to the development of miRNA-based therapeutic strategies for bone disorders. As with other regulatory molecules, miRNAs are frequently subject to change during the development of human diseases. In this regard, we identified a subset of miRNAs with altered expression in osteoporotic bone and demonstrate the functional involvement of some of those miRNAs in the regulation of bone formation and the pathways regulating the progression of osteoporosis. We also have depicted an overview of miRNAs in the human bone tissue and in primary bone cells. Furthermore, we have identified genetic variants in human osteoblast-related miRNAs associated with bone mineral density and this association was functionally demonstrated in bone and osteoblast samples. This work has provided evidences of the marked complexity behind this regulatory system and opens novel prospect for research and therapy.
En l’àmbit de l’estudi de l’òs, els microRNAs (miRNAs) han estat descrits com factors claus en la regulació de la formació, remodelatge i homeòstasis de l’ òs. La identificació de miRNAs implicats en la funció esquelètica és imprescindible pel desenvolupament de noves estratègies terapèutiques, basades en miRNAs, dirigides al tractament de malalties òssies. Com en el cas d’altres molècules reguladores, els miRNAs poden patir modificacions durant el desenvolupament de malalties humanes. En aquest sentit, hem identificat un grup de miRNAs amb una expressió alterada en l’òs osteoporòtic i hem demostrat la implicació funcional d’algun d’aquests miRNAs en la regulació de la formació òssia i els mecanismes pels quals es produiria l’osteoporosi. Alhora, també hem ofert una visió general dels miRNAs presents en el teixit ossi humà i en les cèl·lules òssies. També hem identificat variants genètiques dins de les seqüències de miRNAs expressats en osteoblasts, que han estat associades amb la densitat mineral òssia. A més a més, aquesta associació ha estat funcionalment demostrada en òs i osteoblasts. Aquest treball reflexa l’elevada complexitat que hi ha darrera del sistema regulador per miRNAs i obre nous camins per la recerca i la teràpia.

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Chen, Yong. "Comparative Effectiveness of Alendronate and Risedronate on the Risk of Non-Vertebral Fractures in Older Women: An Instrumental Variables Approach: A Dissertation". eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/582.

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Osteoporosis is a significant public health problem in the U.S. It not only affects the physical well-being of the older women but also creates a substantial financial burden for the health care system. The mainstay of osteoporosis medications is bisphosphonate treatment of which alendronate and risedronate are the most commonly prescribed in clinical practice. However, there have been no head-to-head randomized controlled trials (RCTs) evaluating the effects of these two bisphosphonates on fracture outcomes. In the absence of RCTs, observational studies are necessary to provide alternative evidence on the comparative effectiveness between alendronate and risedronate on fracture outcomes. However, existing observational studies have provided inconclusive results partially due to residual confounding from unobserved variables such as patients’ health status or behavior. IV analysis may be one method to address unmeasured confounding bias in observational studies. While it has not been applied in bisphosphonate research, it has been used in research on a variety of other prescription medications. In this dissertation, we applied the IV approach with an IV, date of generic alendronate availability, to evaluate the comparative effectiveness between alendronate and risedronate using observational data. This dissertation improved current research in several ways. First, we extended the IV approach to research on bisphosphonates. Second, compared with the current observational studies on bisphosphonates, this dissertation may more accurately estimate the relative effects between alendronate and risedronate because IV analysis is not subject to unmeasured confounding bias. Third, the study results extended the current evidence of the comparative effectiveness between the two most commonly prescribed bisphosphonates. Finally, we proposed and provided empirical evidence of a new IV that might be used for future prescription drug research. The finding of this dissertation can be summarized from three aspects. First, we found that the evidence supported the validity of the date of generic availability as an IV in the study of bisphosphonates. Second, applying IV approach to study the comparative effectiveness of alendronate and risedronate, we found that alendronate and risedronate were comparable to reduce the risk of 12-month non-vertebral fractures in older women. Since generic alendronate is availability on the market while generic risedronate is not, promoting the use of alendronate may help reduce the healthcare cost and not sacrifice the clinical effectiveness. Finally, by comparing the proposed IV with a popular IV-physician preference, we found that both the calendar time IV based on the date of generic availability and the physician preference appeared to be valid. It might be practically easier to use the calendar time IV than the physician preference IV.

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Windolf, Markus [Verfasser]. "Fracture fixation in osteoporotic bone / Markus Windolf". Ulm : Universität Ulm, 2014. http://d-nb.info/118442988X/34.

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Castillón, Bernal Pablo. "Implementación de una unidad de trauma geriátrico". Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670446.

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Introducció L'any 1990 es van produir 1,6 milions de fractures de maluc a tot el món i s'estima que aquesta xifra augmentarà a 6 milions l'any 2050. A la Unió Europea es produeixen 600.000 fractures de maluc a l'any, aproximadament, amb un cost global anual de 13.000 milions d'Euros. La incidència a Espanya és de 517 casos per cada 100.000 habitants i per any. L'edat mitjana de 82 anys i un 78% dels pacients són de sexe femení. Els objectius del tractament de la fractura de maluc són preservar la vida i aconseguir una recuperació funcional que permeti el pacient integrar-se de nou en el seu medi habitual. Però, en aquests pacients, la taxa de mortalitat s'eleva durant el primer any d'un 8,4% a un 36%. A l'any de la fractura el 50% presenten dificultats per caminar, el 38-39% presenten dificultat per fer transferències i el 17-19% presenten dificultats per a l’higiene. Fins a un 90% dels pacients presenten múltiples comorbiditats, entre les quals la malaltia pulmonar obstructiva crònica, la demència, la hipertensió arterial, la patologia cardíaca isquèmica i la diabetis són les més comunes. Les característiques d'aquests pacients, ancians i amb múltiples comorbiditats, va fer sorgir la idea de proporcionar-los una atenció compartida entre cirurgians ortopèdics i geriatres. Aquesta idea inicial ha evolucionat a la tendència actual d'implementar unitats de ortogeriatria que integrin un tractament multidisciplinari. En aquest model a geriatres i traumatòlegs se sumen també anestesistes, rehabilitadors, fisioterapeutes, infermeres i nutricionistes, entre d'altres. Objectius L'objectiu principal d'aquesta tesi doctoral és determinar la demora per a intervenció quirúrgica dels pacients amb fractura de fèmur proximal després de la implementació d'una unitat de ortogeriatria. Els objectius secundaris són determinar el temps d'estada hospitalària, la mortalitat intrahospitalària i als 30 dies, i els reingressos que es produeixen per complicacions mèdiques i traumatològiques. Material i mètodes Durant l'any 2013 (juny-desembre), 2014 i 2015, van ingressar al nostre servei 534 fractures de maluc, de manera consecutiva. Mentre que en els anys 2011, 2012 i 2013 (gener-maig), quan encara no existia la Unitat de Traumatologia Geriàtrica (UTG) van ingressar 501. Les dades recollides prospectivament en el segon període, després de la implementació de la UTG, han estat comparats amb les dades dels pacients que van ingressar en el primer període. Resultats La demora mitjana per a ser intervingut quirúrgicament prèviament a la implementació de la UTG va ser de 2,27 dies (DE = 2,35), mentre que posteriorment va ser de 1,84 (DE = 1,73). (P = 0,0004). L'estada mitjana prèviament a la implementació de la UTG va ser de 11,39 dies (DE = 9,05), mentre que posteriorment va ser de 10,08 (DE = 5,43). (P = 0,0024). La mortalitat en els primers 30 dies després de la fractura de maluc, prèviament a la implementació de la UTG va ser del 7,7%, mentre que posteriorment va ser de l'4,8%. (P = 0,027). Conclusió La implementació d'una unitat de ortogeriatria, per al tractament dels pacients amb fractura de fèmur proximal, que inclou un conjunt de mesures entre les que destaquen la introducció de circuits ràpids de tractament, tractament multidisciplinari integrat i protocols de rehabilitació primerenca postoperatòria, ha permès disminuir de 2,27-1,84 dies el temps de demora mitjà per ser intervingut quirúrgicament després de l'ingrés. El temps d'estada hospitalària s'ha reduït en un temps mitjà d'un dia. La mortalitat dels pacients als 30 dies s'ha reduït en un 2,9%. Els reingressos per complicacions mèdiques o quirúrgiques no s'han incrementat.
Introducción En el año 1990 se produjeron 1,6 millones de fracturas de cadera en todo el mundo y se estima que esa cifra aumentará a 6 millones en el año 2050. En la Unión Europea se producen 600.000 fracturas de cadera al año, aproximadamente, con un coste global anual de 13.000 millones de Euros. La incidencia en España es de 517 casos por cada 100.000 habitantes y por año. La edad media de 82 años y un 78% de los pacientes son de sexo femenino. Los objetivos del tratamiento de la fractura de cadera son preservar la vida y conseguir una recuperación funcional que permita al paciente integrarse de nuevo en su medio habitual. Pero, en estos pacientes, la tasa de mortalidad se eleva durante el primer año de un 8,4% a un 36%. Al año de la fractura el 50% presentan dificultades para caminar, el 38-39% presentan dificultades para realizar transferencias y el 17-19% presentan dificultades para el aseo. Hasta un 90% de los pacientes presentan múltiples comorbilidades, entre las que la enfermedad pulmonar obstructiva crónica, la demencia, la hipertensión arterial, la patología cardiaca isquémica y la diabetes son las más comunes. Las características de estos pacientes, ancianos y con múltiples comorbilidades, hizo surgir la idea de proporcionarles una atención compartida entre cirujanos ortopédicos y geriatras. Esa idea inicial ha evolucionado a la tendencia actual de implementar unidades de ortogeriatría que integren un tratamiento multidisciplinar. En este modelo a geriatras y traumatólogos se suman también anestesistas, rehabilitadores, fisioterapeutas, enfermeras y nutricionistas, entre otros. Objetivos El objetivo principal de esta tesis doctoral es determinar la demora para intervención quirúrgica de los pacientes con fractura de fémur proximal tras la implementación de una unidad de ortogeriatría. Los objetivos secundarios son determinar el tiempo de estancia hospitalaria, la mortalidad intrahospitalaria y a los 30 días, y los reingresos que se producen por complicaciones médicas y traumatológicas. Material y métodos Durante el año 2013 (Junio-Diciembre), 2014 y 2015, ingresaron en nuestro servicio 534 fracturas de cadera, de forma consecutiva. Mientras que en los años 2011, 2012 y 2013 (Enero-Mayo), cuando todavía no existía la Unidad de Traumatología Geriátrica (UTG) ingresaron 501. Los datos recogidos prospectivamente en el segundo periodo, tras la implementación de la UTG, han sido comparados con los datos de los pacientes que ingresaron en el primer periodo. Resultados La demora media para ser intervenido quirúrgicamente previamente a la implementación de la UTG fue de 2,27 días (DE=2,35), mientras que posteriormente fue de 1,84 (DE=1,73). (p=0,0004). La estancia media previamente a la implementación de la UTG fue de 11,39 días (DE=9,05), mientras que posteriormente fue de 10,08 (DE=5,43). (p=0,0024). La mortalidad en los primeros 30 días tras la fractura de cadera, previamente a la implementación de la UTG fue del 7,7%, mientras que posteriormente fue del 4,8%. (p = 0,027). Conclusión La implementación de una unidad de ortogeriatría, para el tratamiento de los pacientes con fractura de fémur proximal, que incluye un conjunto de medidas entre las que destacan la introducción de circuitos rápidos de tratamiento, tratamiento multidisciplinar integrado y protocolos de rehabilitación temprana postoperatoria, ha permitido disminuir de 2,27 a 1,84 días el tiempo de demora medio para ser intervenido quirúrgicamente tras el ingreso. El tiempo de estancia hospitalaria se ha reducido en un tiempo medio de un día. La mortalidad de los pacientes a los 30 días se ha reducido en un 2,9%. Los reingresos por complicaciones médicas o quirúrgicas no se han incrementado.
Introduction In 1990, there were 1.6 million hip fractures worldwide. This number is expected to reach 6 million by 2050. In the European Union, osteoporosis causes approximately 600.000 hip fractures per year. The annual estimated economic burden for healthcare systems is 13.000 million Euros. The incidence of hip fractures in Spain is 517 cases per 100.000 inhabitants and year. The average age is 82 years and 78% are women. The goal of hip fracture treatment is to return the patient to preoperative levels of function, facilitating return to pre-fracture residence and supporting long-term wellbeing. Mortality rates in hip fracture patients rise from 8.4 to 36% in the first year after surgery. One year after the fracture, 50% have difficulties in walking, 38-39% are not able to transfer from a bed to a chair and 17-19% require aids for bathing and grooming. Up to 90% of patients have several comorbidities. Commonly, these include chronic obstructive pulmonary disease, dementia, high blood pressure, ischemic heart disease, and diabetes. Elderly patients with several comorbidities could benefit from shared care approaches provided by orthopedic surgeons and geriatricians. This cooperation has triggered the current trend of implementing orthogeriatric units that integrate multidisciplinary teams. In this model, several disciplines, besides surgeons and geriatricians, are involved in the care of the patients including anesthesiologists, physical therapists, nurses, and nutritionists. Objectives The main objective of this study is to determine the delay for surgical intervention of patients with proximal femur fracture after the implementation of an orthogeriatric unit. Secondary objectives are to determine the length of hospital stay, in-hospital and 30-day mortality, and readmissions resulting from medical and trauma complications. Material and methods During 2013 (June-December), 2014, and 2015, 534 consecutive hip fractures were treated in our hospital. While in 2011, 2012, and 2013 (January-May), before the orthogeriatric unit (OGU) was created, 501 hip fractures were treated. Data collected prospectively in the second period, after the implementation of the OGU, have been compared with the first period data. Results The mean delay to undergo surgery before the implementation of the OGU was 2.27 days (SD = 2.35), compared to 1.84 (SD = 1.73). (p = 0.0004) for the second period. The average in-hospital stay before the implementation of the OGU was 11.39 days (SD = 9.05), compared to 10.08 (SD = 5.43). (p = 0.0024) after the orthogeriatric model of care was established. 30-day mortality rate after hip fracture, before OGU implementation, was 7.7%, and 4.8% afterward. (p = 0.027). Conclusion The implementation of an orthogeriatric unit for the treatment of patients with a hip fracture which requires a series of measures including the introduction of fast treatment circuits, integrated multidisciplinary treatment, and early postoperative rehabilitation protocols, has allowed a decrease from 2.27 to 1.84 days in the average time to surgery after admission. The length of hospital stay was reduced by an average time of one day. 30-day mortality was reduced by 2.9%. Readmissions for medical or surgical complications did not increase.

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Herman, Elizabeth O'Brien. "The Use of Osteoporotic Medications Following a Fracture". VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd_retro/118.

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OBJECTIVE:To compare and contrast patients that receive treatment following an osteoporotic fracture to those patients that do not. METHODS:Data were taken from the Medical Expenditures Panel Survey (MEPS). Subjects who reported a wrist, vertebral, or hip fracture were identified. Prescription data were assessed for these subjects and two groups were identified: those who received treatment following a fracture and those who did not. RESULTS:The final sample consisted of n=129 subjects. Of these subjects, only 38% received treatment following an osteoporotic fracture. The only variable showing significant effects on treatment were type of insurance coverage. There was evidence of a relationship for other variables: race, inability to obtain necessary prescription medicines, family income, vertebral fracture and patient's perceived health.CONCLUSIONS: Overall treatment rates following a fracture remain low. Substantial efforts should be made to close the gap between guideline recommendations and clinical practice.

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Borgström, Fredrik. "Health economics of osteoporosis /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-781-2/.

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Machado, Luana Gerheim. "Gordura visceral medida por DXA está associada com risco aumentado de fraturas não vertebrais em mulheres idosas não obesas: São Paulo Ageing e Health (SPAH) Study". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-15122017-120924/.

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Introdução: O papel protetor da obesidade sobre a saúde óssea tem sido questionado, uma vez que a gordura visceral apresenta um efeito deletério sobre o osso. No entanto, até o momento, não existem estudos que avaliaram a associação entre a gordura visceral medida por absorciometria por dupla energia de raios X (DXA) com o risco de fraturas. Objetivo: Investigar a associação entre gordura visceral medida por DXA e incidência de fraturas não vertebrais em mulheres idosas da comunidade. Métodos: Este estudo de coorte longitudinal prospectivo de base populacional avaliou 433 mulheres com 65 anos ou mais. Um questionário clínico, incluindo história pessoal de fratura não vertebral por fragilidade foi realizado na avaliação inicial e após um tempo médio de seguimento de 4,3 anos. Todas as fraturas incidentes durante este período foram confirmadas por radiografia da região afetada. O tecido adiposo visceral (VAT) foi medido na região androide por DXA de corpo total através de um software específico. Modelos de regressão logística foram utilizados para avaliar a associação entre gordura visceral e fraturas não vertebrais. Resultados: A média de idade era de 72,8 ± 4,7 anos e 28 fraturas não vertebrais osteoporóticas foram identificadas após um período médio de seguimento de 4,3 ± 0,8 anos. De acordo com a classificação de Lipschitz para o estado nutricional de idosos, 38,6% das mulheres eram não obesas (IMC <= 27 kg/m²) e 61,4% foram consideradas como sobrepeso/obesas (IMC > 27 kg/m²). Após o ajuste para idade, raça, fratura prévia e densidade mineral óssea (DMO), o VAT (massa, área e volume) teve uma associação significativa com a incidência de fraturas não vertebrais apenas em mulheres idosas não obesas (VAT massa: OR 1,42, IC 95% 1,09-1,85, p = 0,010; VAT área: OR 1,19, IC 95% 1,05-1,36, p = 0,008; VAT volume: OR 1,40, IC 95% 1,09-1,80, p = 0,009). Conclusão: Este estudo sugere um efeito negativo da adiposidade visceral sobre a saúde óssea em mulheres não obesas.
Introduction: The protective effect of obesity on bone health has been questioned because visceral fat has been demonstrated to have a deleterious effect on bone. However, to date, there have been no studies evaluating the association between visceral fat measured by dual-energy Xray absorptiometry (DXA) with fracture risk. Objective: The aim of this study was to investigate the association of visceral fat measured by DXA with the incidence of non-spine fractures in community-dwelling elderly women. Methods: This longitudinal prospective population-based cohort study evaluated 433 community-dwelling women aged 65 years or older. A clinical questionnaire, including personal history of a fragility fracture in non-spine osteoporotic sites, was administered at baseline and after an average of 4.3 years. All incidences of fragility fractures during the study period were confirmed by affected-site radiography. Visceral adipose tissue (VAT) was measured in the android region of a whole-body DXA scan through a specific software. Logistic regression models were used to estimate the relationship between visceral fat and non-spine fractures. Results: The mean age was 72.8 ± 4.7 years, and 28 incident non-spine osteoporotic fractures were identified after a mean follow-up time of 4.3 ± 0.8 years. According to the Lipschitz classification for nutritional status in the elderly, 38.6% of women were nonobese (BMI <= 27 kg/m²) and 61.4 % were obese/overweight (BMI > 27 kg/m²). After adjusting for age, race, previous fractures, and bone mineral density (BMD), VAT (mass, area, volume) had a significant association with the incidence of non-spine fractures only in nonobese elderly women (VAT mass: OR 1.42, 95 % CI 1.09-1.85, p = 0.010; VAT area: OR 1.19, 95 % CI 1.05-1.36, p = 0.008; VAT volume: OR 1.40, 95 % CI 1.09-1.80, p = 0.009). Conclusion: This study suggests a potential negative effect of visceral adiposity on bone health in nonobese women

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Mitchell, Sarah L. "Quadriceps function in elderly patients after proximal femoral fracture". Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250054.

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Ekman, Anna. "Hips at risk osteoporosis and prevention of hip fractures". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4930-1/.

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Keen, Richard William. "Genetic epidemiology of postmenopausal osteoporosis". Thesis, King's College London (University of London), 2000. https://kclpure.kcl.ac.uk/portal/en/theses/genetic-epidemiology-of-postmenopausal-osteoporosis(15d66e32-f0bb-4b51-9e82-60646699d319).html.

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Henderson, Simon Alan. "Exercise, diet and dynamic bone metabolism in osteoporosis". Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336730.

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Tuck, Stephen Paul. "The pathogenesis of osteoporosis and low trauma fractures in men". Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438492.

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Karlsson, Elin. "Investigation and treatment after an osteoporotic fracture: : A survey of the Fracture Liaison Service in Örebro County". Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-72999.

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Introduction: An osteoporotic fracture affects every other woman and every fourth man in Sweden. To meet the needs, Örebro County implemented in 2007 a fracture liaison service(FLS) to identify, investigate and treat these patients. Aim: To evaluate the efficacy of the FLS in Örebro County by reporting the prevalence ofbone mineral density testing and anti-osteoporotic treatment initiation following a low traumafracture. Secondary aim was to evaluate adherence to treatment after 12 months. Methods: 1269 medical records were retrospectively examined for all patients, 50-85 yearsold, with a fractured wrist, upper arm, hip, pelvis or vertebra in Örebro County in 2016.Patient characteristics and continuation through the FLS was studied. Primary objectives wereall descriptive, but various subgroups were compared using chi-square and independent ttests.Limit of significance at p<0.05. Results: 738 patients were eligible for inclusion (mean age 71.00 (±9.16) years, 76.6%women). 391 (53.0%) were referred for investigation, of which 348 (89.0%) attended. 253(72.7%) of the measured patients had indication for treatment, later prescribed to 76.7% ofthese, mainly once weekly oral bisphosphonates (64.4%). Adherence after 12 months wasavailable for 176 patients, of which 119 (67.6%) were still persistent. Conclusion: The FLS in Örebro County seems to be in line with national and internationalcounterparts. Still, there is room for improvement. The major gap appears to be identificationand referral for investigation of patients at risk of osteoporosis. Once passed the identificationstep, the losses through the program are in much smaller proportions.

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Pilon, Danielle. "Oral anticoagulants and the risk of an osteoporotic fracture among the elderly". Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33823.

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Background. Oral anticoagulants are associated with a decrease in bone mass density. Our study evaluates the association between an osteoporotic fracture and oral anticoagulants.
Methods. We conducted a case-control study on subjects aged 70 years and older enrolled in the Quebec health insurance plan between 1992 and 1994. Incident cases of an osteoporotic fracture (index event) were identified by ICD-9 codes and surgical procedure codes. Exposure defined as one or more prescriptions of oral anticoagulants dispensed before the index event. Ten controls for each case, matched by age and date of index event, were selected.
Results. Among 1,523 cases, 48 (3.2%) were exposed to oral an anticoagulant; among 15,205 controls, 461 (3.0%) were exposed (adjusted odds ratio: 1.1, 95% CI: 0.8--1.4). These negative results persisted after stratifying the exposure into the cumulative dose and duration of treatment.
Conclusions. Oral anticoagulants are not significantly associated with an osteoporotic fracture in the elderly.

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Beavan, S. R. "The biochemical and genetic basis of ethnic differences in osteoporotic fracture incidence". Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596507.

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The aim of this thesis was a preliminary investigation of nutritional and biochemical factors which may be implicated in ethnic differences in fracture risk. Investigation of polymorphic loci of the vitamin D receptor gene revealed that the frequency of B and t alleles was considerably greater in the British subjects than in their Gambian or Chinese counterparts (p<0.001). The frequency of the "s" allele of the polymorphic SP1 binding site in the collagen 1α1 gene was also considerably greater in the British subjects than in the Gambian (p<0.02) or Chinese (p<0.001) subjects. The vitamin K status of bone, indicated by the γ-carboxylation of plasma osteocalcin, was determined in eleven premenopausal women of each group and in postmenopausal Gambian (n=50), British (n=31) and Chinese (n=23) subjects. In all groups, undercarboxylation was significantly higher post- than premenopause, but this was related to the higher total osteocalcin concentration present postmenopause. After consideration of differences in total osteocalcin, undercarboxylation was highest in the British, intermediate in the Gambian and lowest in the Chinese subjects irrespective of menopausal status. Possible determinants of osteocalcin γ-carboxylation were investigated. There was a direct relationship between plasma vitamin K concentration and osteocalcin γ-carboxylation in the British subjects, and a direct relationship between plasma triglyceride concentration and osteocalcin carboxylation in the Gambian and Chinese subjects. Apolipoprotein E2 allele was associated with increased γ-carboxylation in the British and Chinese subjects, but there was little indication of a an influence of plasma vitamin D concentration. Differences in plasma vitamin K concentration were observed between the ethnic groups, being significantly higher in the postmenopausal Chinese compared with the British (117% p≤0.0001) and Gambian subjects (103% p≤0.0001). These data suggest genetic differences may exist in calcium homeostasis and the collagen structure of bone, along with differences in vitamin K status and the γ-carboxylation system of osteoblasts, which may be implicated in ethnic variation in osteoporotic fracture risk.

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KATO, FUMIHIKO, NAOKI ISHIGURO, MASAAKI MACHINO, KEIGO ITO, YASUTSUGU YUKAWA i HIROAKI NAKASHIMA. "COMBINED POSTERIOR-ANTERIOR SURGERY FOR OSTEOPOROTIC DELAYED VERTEBRAL FRACTURE WITH NEUROLOGIC DEFICIT". Nagoya University School of Medicine, 2014. http://hdl.handle.net/2237/20549.

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Beavan, Siân Rachel. "The nutritional and biochemical basis of ethnic differences in osteoporotic fracture incidence". Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.625086.

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Hartikka, H. (Heini). "Genetic factors in bone disorders:osteogenesis imperfecta, juvenile osteoporosis and stress fractures". Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:951427718X.

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Abstract Genetic factors and their resulting phenotypes were evaluated in three different bone disorders: osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), and stress fractures. The spectrum of the OI phenotypes caused by mutations in the COL1A1 and COL1A2 genes is well defined, but the mechanisms by which the variations affect the hearing phenotype are not well-known. A total of 54 Finnish OI patients with previously diagnosed hearing loss, or aged 35 or more years, were analyzed here for mutations in COL1A1, or COL1A2. Altogether, 49 mutations were identified, of which 41 were novel. No correlation was observed between the mutated gene, or the mutation type, and the hearing pattern. This indicates that the basis of hearing loss in OI is complex, and is a result of multifactorial, still unknown genetic effects, or of variable expressions of the COL1A1 and COL1A2 genes. JIO presents peri-pubertally as an acute symptomatic osteoporosis (bone pain and fractures) in otherwise healthy children, and no underlying cause has yet been identified for this disorder. Here, the analysis of the low-density lipoprotein receptor-related protein 5 gene (LRP5) in 20 patients with JIO revealed two missense mutations (A29T and R1036Q) and one frameshift mutation (C913fs) in 3 of the patients. The LRP5 gene has recently been shown to be also involved in osteoporosis-pseudoglioma syndrome and a high-bone-mass phenotype. Stress fractures are a significant problem among athletes and soldiers. Genetic factors may increase the fracture risk, but no susceptibility genes have yet been identified. Seven genes involved in bone metabolism, or pathology, were studied in terms of their roles in stress fracture. No disease-causing, or predisposing variations were found in the candidate gene, or association analyses, but a highly significant association was found between the phenotype and a vitamin D receptor (VDR) haplotype, TGT, which is composed of three polymorphic sites, FokI, BsmI and TaqI. We showed that femoral neck stress fractures are associated with a certain VDR haplotype, accounting for a five-fold increase in the risk of developing stress fractures, with an associated attributable risk of 12%. The results of this study show that genetic factors play a role in different pathological bone phenotypes. These findings provide new information on the pathogenesis of the disorders and for the development of genetic testing and targeted treatment for the disorders.

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Heijckmann, Anna Caroline. "Bone mass and fractures in patients at risk for secondary osteoporosis". Maastricht : Maastricht : University Press Maastricht ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=9701.

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Löfman, Owe. "Osteoporosis in women : epidemiological and diagnostic perspectives /". Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med737s.pdf.

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Razmkhah, Omid. "Effect of sideways impact fall on the osteoporosis fractures of proximal femur". Thesis, Kingston University, 2014. http://eprints.kingston.ac.uk/28910/.

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Hip fracture is the most common reason for admission to an orthopaedic trauma word. It is usually a 'Fragility' fracture caused by a fall affecting an older person with osteoporosis or osteopenia (a condition in which bones lose calcium and become thinner, but not as much as in osteoporosis). The National Hip Fracture Database worldwide reports the average age of a person with hip fracture is 84 years for men and 83 years for women, 76% of fracture occurs in women. By 2050, the worldwide incidence of hip fracture in men is projected to increase by 24% in women and 31% in men. Hip fractures due to sideways falls are a worldwide health problem, especially amongst elderly people. The experienced force to the proximal femur during a fall leading to hip fracture is significantly dependent on density, thickness and stiffness of the body during impact. The process of fracture and healing can only be understood in terms of structure and composition of the bone and also its mechanical properties. Bone fracture analysis investigates to predict various failure mechanisms under different loading conditions. In an effort to improve and assist scientists and researchers to predict the impact damage response of bone structures and estimate femoral fracture load in vitro, an accurate explicit finite element (14E) method has been investigated in this study. In the first part, the main goal is to create a 3D reconstruction and registration of semi-transparent Computed Tomography (CT) scan image data using SIMPLEWARE software. In the second part, effect of cortical thickness and impact velocity on the energy absorption of hip during a fall has been investigated on a 3D model. Additionally composite femora were mechanically tested to failure and regression analyses between measured fracture load and FE-predicted fracture load were performed. The results indicate that this sophisticated technique, which is still early in its development, can achieve precision comparable to that of densitometry and can predict femoral fracture load to within 18% with 95% confidence.

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Smith, Matthew S. "Bone fracture toughness of estrogen deficient rabbits". Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=3094.

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Thesis (M.S.)--West Virginia University, 2003.
Title from document title page. Document formatted into pages; contains x, 100 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 91-96).

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Bidesi, Anup Singh. "Comparison of texture classification methods to evaluate spongy bone texture in osteoporosis /". free to MU campus, to others for purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p1422912.

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Pande, Ira. "Causes and consequences of hip fracture in men". Thesis, King's College London (University of London), 2000. https://kclpure.kcl.ac.uk/portal/en/theses/causes-and-consequences-of-hip-fracture-in-men(936ddf70-60c5-412c-8508-a12c9570ada7).html.

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Seemun, Ray [Verfasser]. "Effects of strontium loaded calcium phosphate cement on osteoporotic fracture defect healing / Ray Seemun". Gießen : Universitätsbibliothek, 2014. http://d-nb.info/1068825987/34.

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Czech, Tori. "Fabrication of Osteogenic Protein-loaded Thermoresponsive Hydrogels and Translational Assessment for Osteoporotic Fracture Healing". NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1614181385140819.

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