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Lifetime fracture risk: An approach to hip fracture risk assessment based on bone mineral density and age
Abstract
Hip fractures occur late in life following a substantial reduction in skeletal mass. If risk for such fractures could be predicted early, efforts to prevent excessive bone loss would be more successful and could be directed at the individuals most likely to be affected. With this objective in mind, we devised an approach to estimating the lifetime risk of a proximal femur fracture based on age and on current femoral bone mineral density, using population-based data from ongoing studies of osteoporosis and fractures among Rochester, Minnesota, women. Our calculations indicate that, at any given age, the lifetime risk of a proximal femur fracture rises as current bone density diminishes. At any given level of femoral bone density, lifetime risk rises with younger age and increasing life expectancy. While these trends seem robust, estimates of risk vary substantially with the assumptions that underlie the model. Consequently, these assumptions must be validated before our findings can be applied clinically to predict risk for individual patients.
... Effective prevention measures should include nonpharmacologic interventions and pharmacologic when necessary [21,22,27]. Non-pharmacologic methods -Reducing fall risk: fall prevention can help prevent osteoporosis complications. ...
... Older patients should be consistently counseled to modify the home environment to improve safety and reduce risk of fall (Removal of obstacles and loose carpets in the living environment, install railings along stairways, etc.) [2,3,4]. -Lifestyle: Patients should be educated to minimize their use of alcohol, caffeine and tobacco [5,6,22]. -Nutrition: Nutrition plays a critical role in reducing the risk of osteoporosis. An adequate calcium, vitamin D and protein intake resulted in reduced bone remodeling. ...
... Supplementation with calcium and vitamin D is a critical component of osteoporosis to improve BMD and to reduce fracture risk. The National osteoporosis foundation recommends that postmenopausal woman consume at least 1200 mg calcium per day [21,22,23]. -Physical exercise: A 2 year study showed that adding a physical exercise program to medication improved BMD significantly and is superior to medication alone [5,6,7]. ...
The healthcare environment is generally perceived as being information rich yet knowledge poor. The healthcare industry collects huge amounts of healthcare data which, unfortunately, are not ―mined‖ to discover hidden information. However, there is a lack of effective analysis tools to discover hidden relationships and trends in data. The information technology may provide alternative approaches to Osteoporosis disease diagnosis. In this study, we examine the potential use of classification techniques on a massive volume of healthcare data, particularly in prediction of patients that may have Osteoporosis Disease (OD) through its risk factors. For this purpose, we propose to develop a new solution approach based on Random Forest (RF) decision tree to identify the osteoporosis cases. There has been no research in using the afore-mentioned algorithm for Osteoporosis patients' prediction. The reduction of the attributes consists to enumerate dynamically the optimal subsets of the reduced attributes of high interest by reducing the degree of complexity. A computer-aided system is developed for this purpose. The study population consisted of 2845 adults. The performance of the proposed model is analyzed and evaluated based on set of benchmark techniques applied in this classification problem.
... However, it is commonly accepted that bone strength is improved by physical activity [5]. It has been shown that the rate of loss of BMD is significantly lower for active individuals than inactive [5,8,9]. For this reason, it is of interest to investigate how maintaining one's daily physical activity routine might protect bone integrity. ...
The incidence and morbidity of femoral fractures increases drastically with age. Femoral architecture and associated fracture risk are strongly influenced by loading during physical activities and it has been shown that the rate of loss of bone mineral density is significantly lower for active individuals than inactive. The objective of this work is to evaluate the impact of a cessation of some physical activities on elderly femoral structure and fracture behaviour. The authors previously established a biofidelic finite element model of the femur considered as a structure optimised to loading associated with daily activities. The same structural optimisation algorithm was used here to quantify the changes in bone architecture following cessation of stair climbing and sit-to-stand. Side fall fracture simulations were run on the adapted bone structures using a damage elasticity formulation. Total cortical and trabecular bone volume and failure load reduced in all cases of activity cessation. Bone loss distribution was strongly heterogeneous, with some locations even showing increased bone volume. This work suggests that maintaining the physical activities involved in the daily routine of a young healthy adult would help reduce the risk of femoral fracture in the elderly population by preventing bone loss.
... 1,2 Nearly, one in four men and one in two women suffer one or more fragility fractures in their lifetime. 3 Dual-energy x-ray absorptiometry (DXA) computed BMD is clinically used to detect osteoporosis. It is known that BMD explains 60%-70% of the bone's mechanical competence and the remaining is contributed by several other factors such as trabecular bone (Tb) strength and microstructural basis. ...
Purpose
Osteoporosis is a bone disease associated with enhanced bone loss, microstructural degeneration, and fracture‐risk. Finite element (FE) modeling is used to estimate trabecular bone (Tb) modulus from high‐resolution three‐dimensional (3‐D) imaging modalities including micro‐computed tomography (CT), magnetic resonance imaging (MRI), and high‐resolution peripheral quantitative CT (HR‐pQCT). This paper validates an application of voxel‐based continuum finite element analysis (FEA) to predict Tb modulus from clinical CT imaging under a condition similar to in vivo imaging by comparing with measures derived by micro‐CT and experimental approaches.
Method
Voxel‐based continuum FEA methods for CT imaging were implemented using linear and nonlinear models and applied on distal tibial scans under a condition similar to in vivo imaging. First, tibial axis in a CT scan was aligned with the coordinate z‐axis at 150 μm isotropic voxels. FEA was applied on an upright cylindrical volume of interests (VOI) with its axis coinciding with the tibial bone axis. Voxel volume, edge, and vertex elements and their connectivity were defined as per the isotropic image grid. A calibration phantom was used to calibrate CT numbers in Hounsfield unit to bone mineral density (BMD) values, which was then converted into calcium hydroxyapatite (CHA) density. Mechanical properties at each voxel volume element was defined using its ash‐density defined on CT‐derived CHA density. For FEA, the bottom surface of the cylindrical VOI was fixed and a constant displacement was applied along the z‐direction at each vertex element on the top surface to simulate a physical axial compressive loading condition. Finally, a Poisson's ratio of 0.3 was applied, and Tb modulus (MPa) was computed as the ratio of average von Mises stress (MPa) of volume elements on the top surface and the applied displacement. FEA parameters including mesh element size, substep number, and different tolerance values were optimized.
Results
CT‐derived Tb modulus values using continuum FEA showed high linear correlation with the micro‐CT‐derived reference values (r ∈ [0.87 0.90]) as well as experimentally measured values (r ∈ [0.80 0.87]). Linear correlation of computed modulus with their reference values using continuum FEA with linear modeling was comparable with that obtained by nonlinear modeling. Nonlinear continuum FEA‐based modulus values (mean of 1087.2 MPa) showed greater difference from their reference values (mean of 1498.9 MPa using micro‐CT‐based FEA) as compared with linear continuum methods. High repeat CT scan reproducibility (intra‐class correlation [ICC] = 0.98) was observed for computed modulus values using both linear and nonlinear continuum FEA. It was observed that high stress regions coincide with Tb microstructure as fuzzily characterized by BMD values. Distributions of von Mises stress over Tb microstructure and marrow regions were significantly different (p < 10–8).
Conclusion
Voxel‐based continuum FEA offers surrogate measures of Tb modulus from CT imaging under a condition similar to in vivo imaging that alleviates the need for segmentation of Tb and marrow regions, while accounting for bone distribution at the microstructural level. This relaxation of binary segmentation will extend the scope of FEA application to assess mechanical properties of bone microstructure at relatively low‐resolution imaging.
... Moreover, hip fractures accounted for 72% of the total cost, while accidental fractures accounted for only 14% [13]. The bone mineral density of the femur is reduced by approximately 1% annually after age 50, and the risk of hip fracture increases with the decrease in bone mineral density [31]. Particularly, elderly women have a higher risk of osteoporosis than elderly men. ...
Background: The prevalence of osteoporosis is increasing with the aging of the population and the socioeconomic burden. The purpose of this study was to determine the socioeconomic burden of osteoporosis in Korea. Methods: The prevalence of osteoporosis was analyzed using 2017 National Patients Sample and Korea National Health and Nutrition Examination Survey data. Direct costs were divided into healthcare and non-healthcare costs, and indirect costs were calculated by assessing the cost of loss of productivity for labor loss due to disease. Results: The prevalence of osteoporosis diagnosis was 1.91% in total, which was 13 times higher in women than in men (3.57% vs. 0.26%). The socioeconomic cost of osteoporosis was 299.1 million USD based on main diagnosis, and the cost was 13 times higher in women than in men (277.6 vs. 21.5 million USD). The total cost based on main and secondary diagnosis was 981.8 million USD. Similarly, the cost was seven times higher in women than in men (862.4 vs. 119.4 million USD). Conclusions: Osteoporosis increases the socioeconomic burden of disease, and it is significantly higher in women than in men. The policy support for the implementation of prevention and management programs would be necessary to reduce the burden of osteoporosis.
... BMD is commonly measured for several important skeletal regions (Kim et al. 2018;Kennel et al. 2020) and it is noted that BMD of different skeletal regions and bones (Wajanavisit et al. 2015) are significantly different among different populations. This may suggest that different contributing factors are involved in the BMD of different regions (Joseph et al. 1988). ...
Bone mineral density is a crucially important index for skeletal health. A low amount of bone density (osteoporosis) is a common health problem among men and especially women. Among different parts of the body, women’s face is the area on which many types of (facial) cosmetics are routinely applied. The aims of this study were to measure the association of cosmetic use with BMD of the lumbar spine and femoral neck among young female students. This is a cross-sectional study on 65 female students in the 2017 academic year. The study participants were students at Shiraz University of Medical Sciences who were selected randomly using phone directory sampling method. Based on the results of multiple linear regression, adjusted for several important covariates, cosmetic use is inversely associated with the BMD z-scores. Lead was significantly associated with trochanteric z-score (B = −0.002 to 95% CI = −0.004 to −0.0003, p = 0.02) and total lumbar z-score (B = −0.002 to 95% CI = −0.004 −0.0005, p = 0.01). In the present study, duration of using cosmetics was significantly associated with BMD of key skeletal regions. The big market of cosmetics in many countries especially those in the Middle East is highly a vastly neglected health issue. Many more observational prospective or interventional studies are required to understand the benefits and hazards caused by cosmetics in women.
... 3 Nearly, one in four men and one in two women suffer one or more fragility fractures in their lifetime. 4 Although hip, forearm, spine, pelvis, distal femur, wrist, and humerus are the common sites for osteoporotic fractures, hip fractures are clinically most devastating ones. 5 Osteoporosis remains undetected until a fracture occurs as bone becomes highly fragile at the advanced stages of the disease and bone imaging plays an important role in the assessment of bone quality and improved diagnosis of osteoporosis. ...
... Consequently, the amount of BMD achieved during childhood and adolescence will account for the risk of osteoporosis and fractures during adulthood [115]. Children not reaching adequate bone accretion have higher risk of fragility fractures (FFs), since, from childhood, they are also predisposed to develop involutional osteoporosis when adults [116]. Human studies on this issue are limited and are mainly performed on specific, restricted, peculiar populations such as the children affected by drug resistant epilepsy (DRE). ...
The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a "poor" quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.
... The net result is demineralisation of the trabecular bone. This weakens the bone and increases the risk of fractures of the hip, spine, distal radius and proximal humerus (Melton, 1988). Total (active OC and inactive OB) resorption surface has been shown to be increased in postmenopausal osteoporosis . ...
The aim of this work was to transfect genetic material encoding the peptide, human calcitonin (hCT) into Caco-2 cells (an intestinal epithelial cell model, Hidalgo et aL, 1989) and to examine secretion, in particular from the basolateral surface. It was expected that information on the intracellular sorting of hCT by the Caco-2 cell model would give valuable insight into peptide processing by GI epithelial cells and have implications for the oral delivery of the peptide. cDNA encoding hCT and a small genomic fragment of the hCT gene, CALC-I were successfully transfected into Caco-2 cells. This was confirmed by resistance of transfected cells to G418, a neomycin analogue. The neomycin gene was a marker for the plasmids with which the cells were transfected, G418 being found to be cytotoxic to parent Caco-2 cells within 14 days. All mammalian expression constructs were also transfected into COS cells. Electroporation of COS cells was validated by transfection of the cells with a plasmid encoding Esherichia coli β-galactosidase. hCT secretion could not be detected in transfected COS cells or Caco-2 cells by immunoprecipitation. However, rat calcitonin (rCT) secretion from the rat medullary thyroid carcinoma cell line, rMTC 6-23 could not be detected by immunoprecipitation using the same method. Radioimmunoassay (RIA) of cell medium and cell lysates subjected to concentration on a Sep-Pak Cig cartridge confirmed secretion of rCT by 6-23 cells. This was found to be 0.32 ± 0.03 ng rCT.mg-1 total cellular protein medium and 0.10 ± 0.01 ng rCT.mg-1 total cell protein for cell lysates. No detectable hCT was found in or secreted from transfected Caco-2 or COS cells. Results are discussed in relation to calcitonin gene expression and suggestions are made as to how one might proceed with the project by examination of gene transcription and subsequent expression of hCT or its precursors in Caco-2 cells.
... A higher prevalence of fragility fractures has been described in white populations [10], especially in non Hispanic-Caucasians [11]; lower rates have been found among black populations [10]. In Europe, the Scandinavian countries have the highest prevalence of fragility fractures [12]. Although it is widely recognized that low bone mass is not the only determinant of bone fragility, the strength of the skeleton is influenced by other bone tissue properties, collectively named "bone quality" [13,14]. ...
... 42 Children who reach lower peak bone accumulation, secondary to medication effects or decreased exposure to vitamin D, have greater rates of involutional osteoporosis over the course of their lifetime. 43 Fractures are the most important long-term sequelae of poor bone health. Increased fracture rates are seen in adult patients with epilepsy. ...
Objective
Antiseizure medications and dietary therapies have associated effects on the endocrine system. We provided an overview of the association between epilepsy treatment and bone health in children with epilepsy. Additionally, we discussed the effects of epilepsy treatment on other endocrine systems including thyroid function, growth, reproduction, and weight.
Findings
The effect of epilepsy on bone health is multifactorial; there are direct and indirect effects of medication and dietary treatments as well as a decrease in physical activity, decreased sunlight exposure, decreased vitamin D levels, and additional comorbidities. Some medications have a greater effect on vitamin D and bone health than others, however all antiseizure medications are associated with lower vitamin D levels in pediatric patients. We have provided practical suggestions for vitamin D surveillance in children with epilepsy as well as replacement strategies. Children with epilepsy have an increased likelihood of additional endocrine disorders including subclinical hypothyroidism, decreased growth, weight abnormalities, reproductive and sexual dysfunction. To a great extent, this is medication specific.
Conclusion
Though more studies are needed to elucidate optimal treatment and monitoring of bone health and other endocrinopathies in children with epilepsy, it is critical that caregivers pay close attention to these issues to provide optimal comprehensive care to their patients.
... The total costs and benefits calculated for the 20 Figure 3) and ...
The Trent Regional Osteoporosis Working Party was set up in July 1989 with the remit to
review the evidence for screening for postmenopausal osteoporosis and to examine the
costs and benefits of prevention using long-term hormone replacement therapy (HRT).
This report details the work done by members of the working party to fulfil that remit and
to submit recommendations about policy to Trent Regional Health Authority.
The report describes the aetiology and risk factors of postmenopausal osteoporosis.
Routine and survey data are used to estimate the mortality and morbidity from the
condition in Trent Region.
On evidence drawn from an extensive literature search the effectiveness of a population
screening and prevention programme is assessed. A maximum effectiveness of 3.9 percent
is derived by combining plausible assumptions for: the proportion of women likely to
accept an invitation for screening, the proportion of true positives discovered by the
screening test, the efficacy of long-term HRT for preventing osteoporotic fractures and the
proportion of women who would comply with long-term HRT.
A review of recent research about the effect of HRT on the relative risks of osteoporotic
fracture, cardiovascular mortality and breast carcinoma is undertaken. Ranges of
plausible assumptions have been derived for the impact of long-term HRT on the health
of a population of postmenopausal women.
The costs and benefits of population screening and prevention for postmenopausal
osteoporosis are quantified based on a 20 year model programme which would offer bone
mineral screening to all women in Trent Region at 50 years. Women assigned to the
highest risk quintile by the screening test would be offered a ten year course of HRT. The
assumptions derived from the literature about the effectiveness of bone mineral screening
and intervention with HRT for prevention of osteoporotic morbidity were applied to the
modelled population.
It was estimated that between 0.5 and 3.9 percent of osteoporotic fractures would be
prevented in anyone year. The number of hip fractures prevented by the entire 20 year
programme would be between 247 and 2800 and the reduction in deaths from hip
fracture is estimated to be less than 240. The maximum potential hospital 'savings' from
the programme was under £1.7 million compared to an estimate for the overall cost of
nearly £13 million.
The costs of screening for and preventing postmenopausal osteoporosis using HRT would
not be offset by any potential reduction in hospital inpatient costs from prevented
fractures. The question remains whether the benefits of reduced mortality and morbidity
and of improved quality of life would justify the costs of a population prevention
programme.
It is recommended that a population screening and prevention programme should not be
established yet but that general practitioners should: be provided with guidelines about all
aspects of osteoporosis prevention and the indications for bone mineral screening and
long-term HRT.
This report also makes recommendations for further research where deficiencies in
current knowledge and areas of uncertainty have been found about screening and
osteoporosis prevention.
... Approximately 95% of the total bone development occurs by 18 years of age with a peak of bone mineral density (BMD) that occurs by 25 and declines after 40 (Kemper, 2000). Therefore, any process that reduces bone mass or alters mineralization during the early developmental period or early adulthood will likely result in an increased susceptibility to bone fractures in the long-term (Melton et al., 1988). ...
Individuals with a history of epilepsy are at higher risk for bone fractures compared to the general population. Although clinical studies support an association between low bone mineral density (BMD) and anti-seizure medications, little is known on whether a history of seizures is linked to altered bone health. Therefore, in this study we tested the hypothesis that bone mass, morphology, and bone mineralization are altered by seizures in genetically epileptic animals and in animals subjected to an episode of status epilepticus. In this study, we used NS-Pten conditional knockout mice (a well-studied genetic model of epilepsy). We used microCT analysis to measure BMD, morphology, and mineralization in NS-Pten+/+ (wildtype) and NS-Pten−/− (knockout) mice at 4 and 8 weeks, as well as adult Kv4.2+/+ and Kv4.2−/− mice. We measured BMD, bone morphology, and mineralization in adult NS-Pten+/+ mice that received status epilepticus through kainic acid (20 mg/kg intraperitoneal). Further, we measured locomotion for NS-Pten+/+ and NS-Pten−/− mice at 4 and 6 weeks. We found that NS-Pten−/− mice exhibited low BMD in the tibial metaphysis and midshaft compared to non-epileptic mice. Morphologically, NS-Pten−/− mice exhibited decreased trabecular volume fraction, and endocortical expansion in both the metaphyeal and diaphyseal compartments. In the midshaft, NS-Pten−/− mice exhibited reduced tissue mineral density, indicating impaired mineralization in addition to morphological deficits. NS-Pten−/− mice exhibited hyperactivity in open field testing, suggesting low bone mass in NS-Pten−/− mice was not attributable to hypoactivity. Differences in BMD were not observed following kainate-induced seizures or in the Kv4.2−/− model of seizure susceptibility. Our findings suggest that deletion of Pten in the brain results in impaired bone mass and mineralization, which may contribute to weaker bones and thereby a higher fracture risk.
... The modest changes in bone mineral density observed with vitamin D supplements are unlikely to be the sole explanation for the reduced fracture rate. In the elderly most non-vertebral fractures occur as a result of falls [6] and it is noted that in this population age-related factors other than bone mineral density are important determinants of fracture risk [7]. ...
... The incidence of wrist fracture rises from age 50 to 65 years and then reaches a plateau after age 65 years (Melton III et al., 1988;Kristinsdottir et al., 2001), but why this occurs ...
The upper extremities are often used to protect the head and thorax by bracing for impact, particularly in falls to the ground. The impulsive loads they impose on the hand and wrist can be substantial, exceeding one body-weight. If the upper extremity then ???gives way??? or flexion buckles at the elbow then a head injury is likely, particularly in the elderly; but if the elbows are fully extended to prevent buckling, then the risk for wrist fracture increases. A current knowledge gap includes the biomechanical factors that determine the threshold load required to flexion-buckle the elbow of an end-loaded and pretensed human upper extremity.
In this thesis we use computer simulations and in vivo experiments to explore how age, gender, initial elbow angle, arm muscle strength and pre-contraction level and lumped contractile properties about a joint affect upper extremity deflection under impulsive end-loading. The experimental results show that gender and age affect the rotational stiffness and damping coefficients of muscles acting about the elbow and shoulder when estimated by dynamic optimization. The pre-contraction levels of arm and shoulder muscles significantly affected these coefficients. Computer simulations predict that advancing age, female gender and insufficient arm and shoulder muscle pre-contraction level adversely affect upper extremity buckling loads. Kinetic, kinematic and myoelectric studies suggest the speed of propagation of the impulsive load along the upper extremity is such that arm and shoulder muscles must be pretensed prior to impact: no neuromuscular reflex is rapid enough to increase arm muscle tensile stiffness to prevent flexion buckling. Pre-contraction level and gender significantly affected the rate of propagation of an impulse along the upper extremity.
The findings provide a framework for better understanding how biomechanical factors determine whether or not an arm will buckle when end-loaded during a fall arrest. We conclude that in order to help safely arrest falls older women and men need to avoid using hyperextended arms when possible, use an adequate pre-contraction level in the arm muscles to prevent buckling, and maintain as much arm protraction strength as possible, perhaps most conveniently by regular push-up exercises.
... Previous studies have identified a range of intrinsic and situational risk factors for hip fractures, including lower limb dysfunction [5,6], impaired balance and mobility [7,8], high frequency of falls [9,10], low bone mineral density [11,12], cognitive impairment [13,14], and medication use [14,15]. A similarly important, but less examined, question is how risk for hip fracture depends on the mechanics of the fall itself. ...
Hip fracture risk is increased by landing on the hip. We examined factors that contribute to hip impact during real-life falls in long-term care facilities. Our results indicate that hip impact is equally likely in falls initially directed forward as sideways and more common among individuals with dependent Activities of Daily Living (ADL) performance.
The risk for hip fracture in older adults increases 30-fold by impacting the hip during a fall. This study examined biomechanical and health status factors that contribute to hip impact through the analysis of real-life falls captured on video in long-term care (LTC) facilities.
Over a 7-year period, we captured 520 falls experienced by 160 residents who provided consent for releasing their health records. Each video was analyzed by a three-member team using a validated questionnaire to determine whether impact occurred to the hip or hand, the initial fall direction and landing configuration, attempts of stepping responses, and use of mobility aids. We also collected information related to resident physical and cognitive function, disease diagnoses, and use of medications from the Minimum Data Set.
Hip impact occurred in 40 % of falls. Falling forward or sideways was significantly associated with higher odds of hip impact, compared to falling backward (OR 4.2, 95 % CI 2.4-7.1) and straight down (7.9, 4.1-15.6). In 32 % of sideways falls, individuals rotated to land backward. This substantially reduced the odds for hip impact (0.1, 0.03-0.4). Tendency for body rotation was decreased for individuals with dependent ADL performance (0.43, 0.2-1.0).
Hip impact was equally likely in falls initially directed forward as sideways, due to the tendency for axial body rotation during descent. A rotation from sideways to backward decreased the odds of hip impact 10-fold. Our results may contribute to improvements in risk assessment and strategies to reduce risk for hip fracture in older adults.
... Un moyen utile d'estimer l'impact global d'une maladie consiste à déterminer son risque de survenue au cours de la vie restante d'individus (appelée «lifetime risk» en anglais). Le risque de survenue d'une fracture de hanche a déjà été estimé aux Etats-Unis, en Australie et en Europe (Suède et Danemark) (4,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Il s'élève ainsi entre 11 % et 22 % pour des femmes de 50 ou 60 ans, dépendant en partie de l'approche utilisée et des taux d'incidence et de mortalité de la population étudiée. ...
... The challenge in the literature of this area is to obtain a risk function with high accuracy that predicts fracture risk based on major risk factors. Although there are a few such equations available (e.g., Tosteson et al., 1990;Melton 1988;Ross et al., 1988 1 ), questions remain about the validity of these models and applicability for different populations. ...
... Despite the lack of significant differences in bone turnover measures with raloxifene treatment, our results show that raloxifene improves bone material properties, potentially through direct action of raloxifene on the bone matrix, and may prevent the induction of diabetes in female ZDSD rats. The risk of diabetes increases with age [27], as does the risk for bone fragility fractures [28]. If these results are supported by future experimental and clinical studies, they suggest that raloxifene could be a useful drug to prevent skeletal fragility in diabetes with an added benefit of ameliorating the diabetic condition. ...
Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.
... Less well known is the fact that bilateral castration in the first years after the menopause will ac celerate the bone loss, since the re sidual steroid secretion by the ovaries, especially of ovarian androgens, is eliminated as a result [43]. The ovary is not the inactive and useless organ that it is sometimes thought to be after the menopause; instead, it continues to have a major endocrine physiological function [43][44][45]. ...
... Non-traumatic skeletal fractures are directly related to increased incapacitation, morbidity, and mortality and pose a serious health problem to an aging population [1][2][3]. Several age-related changes in bone morphology and composition have been identified and were subsequently linked to an increased risk of non-traumatic fracture [4][5][6][7]. One such change is the accumulation of advanced glycation end-products (AGEs) within the collagen network of cortical and cancellous bone [8][9][10]. ...
Nonenzymatic glycation (NEG) describes a series of post-translational modifications in the collagenous matrices of human tissues. These modifications, known as advanced glycation end-products (AGEs), result in an altered collagen crosslink profile which impacts the mechanical behavior of their constituent tissues. Bone, which has an organic phase consisting primarily of type I collagen, is significantly affected by NEG. Through constant remodeling by chemical resorption, deposition and mineralization, healthy bone naturally eliminates these impurities. Because bone remodeling slows with age, AGEs accumulate at a greater rate. An inverse correlation between AGE content and material-level properties, particularly in the post-yield region of deformation, has been observed and verified. Interested in reversing the negative effects of NEG, here we evaluate the ability of n-phenacylthiazolium bromide (PTB) to cleave AGE crosslinks in human cancellous bone. Cancellous bone cylinders were obtained from nine male donors, ages nineteen to eighty, and subjected to one of six PTB treatments. Following treatment, each specimen was mechanically tested under physiological conditions to failure and AGEs were quantified by fluorescence. Treatment with PTB showed a significant decrease in AGE content versus control NEG groups as well as a significant rebound in the post-yield material level properties (p<0.05). The data suggest that treatment with PTB could be an effective means to reduce AGE content and decrease bone fragility caused by NEG in human bone.
Background
Osteoporosis is a bone disease related to increased bone loss and fracture‐risk. The variability in bone strength is partially explained by bone mineral density (BMD), and the remainder is contributed by bone microstructure. Recently, clinical CT has emerged as a viable option for in vivo bone microstructural imaging. Wide variations in spatial‐resolution and other imaging features among different CT scanners add inconsistency to derived bone microstructural metrics, urging the need for harmonization of image data from different scanners.
Purpose
This paper presents a new deep learning (DL) method for the harmonization of bone microstructural images derived from low‐ and high‐resolution CT scanners and evaluates the method's performance at the levels of image data as well as derived microstructural metrics.
Methods
We generalized a three‐dimensional (3D) version of GAN‐CIRCLE that applies two generative adversarial networks (GANs) constrained by the identical, residual, and cycle learning ensemble (CIRCLE). Two GAN modules simultaneously learn to map low‐resolution CT (LRCT) to high‐resolution CT (HRCT) and vice versa. Twenty volunteers were recruited. LRCT and HRCT scans of the distal tibia of their left legs were acquired. Five‐hundred pairs of LRCT and HRCT image blocks of 64×64×64$64 \times 64 \times 64 $ voxels were sampled for each of the twelve volunteers and used for training in supervised as well as unsupervised setups. LRCT and HRCT images of the remaining eight volunteers were used for evaluation. LRCT blocks were sampled at 32 voxel intervals in each coordinate direction and predicted HRCT blocks were stitched to generate a predicted HRCT image.
Results
Mean ± standard deviation of structural similarity (SSIM) values between predicted and true HRCT using both 3DGAN‐CIRCLE‐based supervised (0.84 ± 0.03) and unsupervised (0.83 ± 0.04) methods were significantly (p < 0.001) higher than the mean SSIM value between LRCT and true HRCT (0.75 ± 0.03). All Tb measures derived from predicted HRCT by the supervised 3DGAN‐CIRCLE showed higher agreement (CCC ∈$ \in $ [0.956 0.991]) with the reference values from true HRCT as compared to LRCT‐derived values (CCC ∈$ \in $ [0.732 0.989]). For all Tb measures, except Tb plate‐width (CCC = 0.866), the unsupervised 3DGAN‐CIRCLE showed high agreement (CCC ∈$ \in $ [0.920 0.964]) with the true HRCT‐derived reference measures. Moreover, Bland‐Altman plots showed that supervised 3DGAN‐CIRCLE predicted HRCT reduces bias and variability in residual values of different Tb measures as compared to LRCT and unsupervised 3DGAN‐CIRCLE predicted HRCT. The supervised 3DGAN‐CIRCLE method produced significantly improved performance (p < 0.001) for all Tb measures as compared to the two DL‐based supervised methods available in the literature.
Conclusions
3DGAN‐CIRCLE, trained in either unsupervised or supervised fashion, generates HRCT images with high structural similarity to the reference true HRCT images. The supervised 3DGAN‐CIRCLE improves agreements of computed Tb microstructural measures with their reference values and outperforms the unsupervised 3DGAN‐CIRCLE. 3DGAN‐CIRCLE offers a viable DL solution to retrospectively improve image resolution, which may aid in data harmonization in multi‐site longitudinal studies where scanner mismatch is unavoidable.
References: Brickley, M.B. Ives, R. & Mays, S. (2020). The Bioarchaeology of Metabolic Bone Disease, Second Edition
Patients with neurological disorders are at high risk of developing osteoporosis, as they possess multiple risk factors leading to low bone mineral density. Such factors include inactivity, decreased exposure to sunlight, poor nutrition, and the use of medication or treatment that can cause lower bone mineral density such as antiepileptic drugs, ketogenic diet, and glucocorticoids. In this article, mechanisms involved in altered bone health in children with neurological disorders and management for patients with epilepsy, cerebral palsy, and Duchenne muscular dystrophy regarding bone health are reviewed.
One hundred and fourteen trochanteric fractures of the femur were analysed. The ratio between males and females was 3.07. The average age of the patients was 78.6 years for both males and females. Low energy trauma (“simple fall” due to slipping, tripping, stumbling, or due to dizziness.) was the cause in 63 hips (73.2%) in female, in 16 hips (57.1%) in male. Seventy two percent of the females and 62% of the males were injured indoors. Sixteen fractures occurred while the patients were hospitalized for other reasons. There were 86 patients (76.3%) with preexisting diseases which were possibly related to the fracture. The cost of the treatment was \1, 418, 000. We suspected that the cost of the treatment of the trochanteric fractures in Japan was \4, 679, 400, 000.
The prevalence rates of decreased bone mineral density (BMD) in patients with inflammatory bowel disease (IBD) range from 40% to 50%. Osteoporosis, as defined by a BMD
Z score of —2.5, has been reported in a range of 2-30%. There are a paucity of data reporting the fracture incidence rate among patients with IBD. Fractures are a hard endpoint and the main morbidity associated with osteopenia of any cause. Osteoporosis which places subjects at risk for fractures has been a term applied to histomorphometric diagnoses, radiological diagnoses, and most recently to BMD diagnoses. We have recently reported that there is an increased rate of fractures at the hip, ribs and forearm among patients with IBD compared with an age, gender and geographically matched cohort drawn from the general population. We found a tendency towards increased fractures at the spine, but this was not statistically significant.
The following is a discussion of risk factors for the development of osteoporosis and fractures in patients with IBD. Measurable risk factors, such as BMD or serum and urine markers of bone resorption and formation, will be discussed in the context of patients with IBD. Similarly, modifiable risk factors will also be discussed.
Osteoporotic fracture poses a major health problem in an aging population, yet its aetiology is not well established. Much remains to be learned about the role of a number of risk factors. In this paper, the literature is reviewed and suggestions are made for research emphasis.
The actions of estrogens in the brain go well beyond the regulation of reproduction and include effects upon mood, cognitive function, motor coordination, pain, and protection of the brain from certain forms of damage. Multiple receptor mechanisms are believed to be involved, including at least two types of intracellular estrogen receptors (ERα and ERβ) and nonnuclear, nongenomic actions of estrogens that may involve a form of the intracellular receptors or other as-yet-unidentified receptor types. Selective estrogen response modulators (SERMs) interact with these many mechanisms of estrogen action in different ways, acting primarily as agonists or antagonists or having no effects in some cases. For this reason, it is difficult to imagine that SERMs or any other substitute for estradiol itself will mimic all of the brain effects of 17-β estradiol itself. Rather, the challenge is to develop therapeutic strategies that emphasize particular beneficial effects of estrogens on the brain, such as neuroprotection, while minimizing the possible antagonism of other estrogen actions that are beneficial.
Osteoporosis is the most prevalent metabolic bone disease in the elderly and causes much morbidity, mortality and cost in terms of health and social services expenditure. It has been estimated that its prevalence will double by year 2044 and that the prevalence of hip fracture, which is one of the most important consequences of the condition, will increase fourfold by year 2050. Although the menopause in women is an important turning point in the development of osteoporosis, the majority of osteoporosis related fractures occur after the age of 65 years and increase exponentially thereafter (Fig. 10.1).
The central role of oestrogen deficiency in the pathogenesis of postmenopausal bone loss and osteoporosis is well established. The association was first recognised by Fuller Albright in 1941 (Albright et al. 1941) and subsequently Aitken et al. (1973a) reported a reduction in metacarpal bone mass in women who had undergone oophorectomy before the age of 45 years, osteopenia developing within 3–6 years after operation. Hormone replacement therapy is the only treatment for osteoporosis in which prevention of bone loss and reduction in fracture rate in the spine, radius and hip has been definitively established. These considerations make it the therapy of choice in the prevention and treatment of osteoporosis in peri- and postmenopausal women but many questions remain unanswered.
Over 300 years ago Galileo and Vesalius suspected skeletal architecture might depend on mechanical usage [1] and more than 100 years ago Julius Wolff stated the relationship between bone function and its architecture [2]. Therefore, the effects of reduced mechanical usage on bone have been known for a long time. In 1924, J.W. Dowden wrote: “the musculature of a limb is reflected in the bones, so that it is easy to distinguish the long bone of a strong man, by its solidity and powerful ridges for muscular attachment, from the bone of a disuse limb, by the lightness and smoothness of the latter. The results of disuse are rapidly seen, even in the X-ray photographs” [3], In 1941, Albright and colleagues reported the case of a young boy who developed hypercalcemia as a consequence of the immobilization for a fracture. During the 1940s and 1950s, alterations in calcium and phosphorus metabolism were described by Whendon and colleagues in poliomyelitic patients and immobilized volunteers and an elevated rate of bone turnover after fracture was described by Bauer [4] and confirmed by others [5,6].
Osteoporosis is a condition of reduced bone density and increased susceptibility to fractures without abnormal mineralization of bone matrix.1 The World Health Organization (WHO) defines osteoporosis as the presence of a bone mineral density (BMD) at least 2.5 standard deviations below the mean BMD for young adults.2 Osteoporosis affects an estimated 20 million to 25 million people in the United States, particularly postmenopausal women and the elderly of both sexes.3 Its most common serious manifestations are fractures of the hip, forearm, and vertebrae. Measures taken at several critical periods during the life cycle, especially childhood, the climacteric, and old age, have the potential to prevent osteoporotic fractures. Therefore family physicians are in a key position for preventing and treating this disease.
For several decades, vertebroplasty has been performed as an open procedure to augment the purchase of pedicle screws for spinal instrumentation1 and to fill voids resulting from tumor resection.2–5 The procedure introduces bone graft or acrylic cement into vertebral bodies to mechanically augment their structural integrity 2–4,6–12 In some cases, however, the risk of an open procedure is not indicated. It was one such case that served as the impetus for the development of percutaneous vertebroplasty (PV). Percutaneous vertebroplasty achieves the benefits of vertebroplasty without the morbidity associated with an open procedure. Vertebral augmentation is accomplished by injecting polymethylmethacrylate (PMMA) cement into a vertebral body via a percutaneously placed cannula. The procedure was first performed in 1984 by Galibert and Deramond in the Department of Radiology of the University Hospital of Amiens, France,13on a woman, aged 54, who had complained of severe cervical pain for several years.
The most serious manifestations of osteoporosis are proximal femoral fractures, affecting over 250,000 elderly in the United States each year and 890,000 in the European Union in the year 2000 alone. The impact on public health and the resultant cost to the health care system highlight the urgency to identify those parameters significant to accurately predict bone quality and fracture risk at the proximal femur. Determinations of the proximal femur are employed to illustrate relevant applications of vQCT with the potential to be extrapolated to other skeletal sites and the research and development of novel biomaterials that could contribute to the restoration or improvement of bone function. We explain the underpinning of parameters for bone mass, BMD, and bone geometry, as well as the structural indices discriminated by vQCT. We further clarify the benefit of sub-regional analysis (trochanteric region separate from femoral neck region) and of compartmental analysis (cortical bone separate from trabecular bone). In order to gain insight into how these factors contribute to bone fragility, we show how vQCT information combined with finite element modeling (FEM) information, a structural analysis tool, allows for estimation of fracture load under various loading conditions including impact from a fall. We typify unique results obtained from studies on aging, drugs with bone impact, and spaceflight, which is difficult to reveal in vivo without vQCT. We show in vivo how aging results in heterogeneous effects in the trochanteric and femoral neck region and how the impact of long-term spaceflight differs between trabecular and cortical bone. We suggest future directions for vQCT, such as the improvement of accuracy and precision for longitudinal studies, the FEM analysis integration into individual patient evaluation for in vivo assessment of simulated fracture conditions, and the development of additional variables for enhancement of bone fragility evaluations.
The old idea linking calcium to osteoporosis leads the clinician to screen for insufficient dietary calcium intake. However, pharmacological calcium supplements are no more systematically added since the recognition of the importance of vitamin D status before and throughout treatment. Nevertheless, the calcium remains an essential nutrient for bone health whether in primary or secondary prevention. Some impact studies showed that calcium supplementation is likely to have a positive effect on the acquisition and maintenance of bone mass as well as the reduction of bone loss and fracture incidence. Although these effects are more expressive in the presence of vitamin D, the beneficial effect of calcium on peripheral fractures prevention, especially in the elderly deserves to be highlighted. Considering the low rate of 1-year adherence to antiosteoporotic medication, raising awareness of the importance of calcium daily food intake could help improving adherence to treatment. Calcium supplementation is recommended for elderly people and subjects with calcium deficiency.
Objectives: To determine the frequency of osteopenia and osteoporosis using dual energy x-ray absorptiometry in healthy postmenopausal women within five years of onset of menopause and also to compare the menopausal symptoms between two different age groups. Methodology: This cross sectional study was conducted at the outpatient department of Obstetrics and Gynecology, Fauji Foundation Hospital Rawalpindi from January 1st 2010 to May 31st 2010. DXA scan of the lumbar spine (L2- L4) and right hip (femoral neck) was requested. Osteoporosis was defined by a T-score of ≤ -2.5, osteopenia as T-score between -1 and -2.5, and normal BMD as T-score >-1. Menopausal rating scale was used and all findings were recorded in predesigned proformas. Results: Out of a total of 33 subjects, who underwent dual energy x-ray absorptiometry, osteopenia and osteoporosis were found in 22 (66.7%) while only 11 (33.3%) have normal results. We took Null hypothesis H0: π=0.5 against the alternative H1: π>0.5. The test statistics is 22.4 and p value is zero. So H0 is rejected at all significance levels showing that ratio of abnormal DXA scan findings i.e. osteopenia and osteoporosis among healthy postmenopausal women is significantly much higher than normal findings. Also poor concentration, sexual dysfunctions, urinary symptoms, dyspareunia and joint pains were significantly more common in group II: age >50 than group I: age 50 or below (p-value <0.05). Conclusion: Osteopenia and osteoporosis are significantly more common in healthy postmenopausal women in early years of menopause. Menopausal symptoms have a significant correlation with advancing age.
Osteoporosis is a skeletal disease characterized by decreased bone strength. Patients with chronic kidney disease (CKD) have disturbances in bone and mineral metabolism leading to complex changes in bone turnover, mineralization and volume, which has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD) recently. Patients with CKD may have higher prevalence of osteoporosis compared to general population. The coexistence of osteoporosis and CKD-MBD seems to be related to increased fracture risk, leading to increased morbidity and mortality. There is little information about the appropriate pharmacological therapy for osteoporosis in patients with CKD, including the beneficial effect and the safety. This article reviews the current therapeutic approach to osteoporosis in patients with CKD.
The net resource costs and net health benefits of treating perimenopausal women with hormone replacement therapy were evaluated within the framework of cost-effectiveness analysis. Data from the epidemiological literature were used to estimate changes in discounted life expectancy from hip fracture, ischaemic heart disease and breast cancer that are associated with hormone replacement therapy under a variety of assumptions. Economic data were used to estimate changes in total discounted costs that result from the use of hormone replacement therapy. For women with a previous hysterectomy, 10- and 15-year courses of unopposed oestrogen were evaluated. The baseline assumptions for unopposed oestrogen were that breast cancer incidence would be increased for current users by 36% and that deaths from ischaemic heart disease would be reduced by 50% relative to non-users. Under these assumptions, oestrogen replacement therapy was found to be cost-effective, with ratios ranging from $9130 to $12,620 per additional year of life saved. For women who have not had a hysterectomy, 10- and 15-year courses of oestrogen combined with progestin were evaluated. The baseline assumptions for combined therapy were that breast cancer incidence and ischaemic heart disease deaths were unaffected. Under these assumptions, combined therapy was more costly, with ratios ranging from $86,100 to $88,500. Unless combined therapy is found to confer protection against ischaemic heart disease, the most cost-effective strategies for women with no prior hysterectomy may involve screening perimenopausal women to detect women at highest risk of hip fracture followed by selective treatment.
“Efectividad de la medida de densidad ósea y de los tratamientos asociados en la prevención de fracturas”. Proyecto conjunto INAHTA
Es erfolgt eine Knochenstrukturanalyse der proximalen Tibia unter Berücksichtigung verschiedenster radiologischer, biomechanischer und histomorphometrischer Aspekte. Die regionen-, alters- und geschlechtsspezifischen Aspekte dieser Problemregion werden herausgearbeitet. Der eindeutige Nachweis einer regionen-abhängigen Verteilung der Knochendichte und der biomechanischen Eigenschaften in der proximalen Tibia ist eines der Hauptergebnisse der vorliegenden Studie. In der proximalen Tibia besteht eine signifikante Abnahme der Knochendichte von proximal nach distal. Im zentralen Bereich der proximalen Tibia besteht in allen Sektionen im Vergleich zu den anterior/posterior und medial/lateral liegenden Gebieten die niedrigste Knochendichte. In der vorliegenden Studie wurde die proximale Tibia in 3 Etagen (von proximal nach distal) unterteilt. Beim Vergleich der auf diesen Etagen aufgebrachten ROIs (region of interest,jeweils 5 in den beiden proximalen Etagen und 4 im distalen Abschnitt) zeigte sich in den beiden proximalen Etagen lateral (Ebene I anterolateral/ Ebene II posterolateral) die höchste Knochendichte. Im Gegensatz dazu zeigte sich in der distalen Etage anteromedial die höchste Knochendichte. Weiterhin wurden die 3 gängigen Stabilisierungsverfahren für diese Region einer umfangreichen biomechanischen Testung unterzogen. Es zeigte sich, dass der Ilizarov Fixateur bei den verschiedensten Lastfällen meist das instabilste Implantat war. Trotz der biomechanischen Defizite konnten die in der klinischen Studie mit Composite Fixateur versorgten Frakturen trotz erheblichem Weichteilschaden und instabiler Fraktursituation zur Ausheilung gebracht werden. Das LIS-System erwies sich gegenüber der konventionellen Abstützplatte hinsichtlich der biomechanischen Steifigkeit sowohl in der statischen als auch in der zyklischen Testung als gleichwertiges oder sogar biomechanisch günstigeres Implantat. Diese positiven klinischen wie biomechanischen Erfahrungen führen auch zur Förderung der Entwicklung anderer winkelstabiler Fixateur interne-Systeme in den verschiedensten Problemregionen (Pilon tibiale, proximaler und distaler Humerus, distaler Radius). Als wesentliche neue Therapieansätze für das operative Vorgehen in der Problemregion der proximalen Tibia lassen sich die folgenden Gesichtspunkte herausarbeiten: 1) Knochendichteadaptierte Implantat- und Schraubenpositionierung bei der konventionellen Osteosynthese, 2) Knochendichteadaptierte Pin- und Olivendrahtpositionierung bei externen Fixationsverfahren (Ilizarovringfixateur, Fixateur externe) im Bereich der proximalen Tibia, 3) Implantatverbesserungen (LISS-Schraubenkonfiguration und -positionierung, Plattendesign, Umstellungsplatte, Verriegelungsbolzen bei Marknägeln wie UTN, PTN), 4) Prothesenverbesserung (knochendichteadaptiertes Zapfendesign mit 3 Zapfen für die tibiale Komponente).
This new edition of the well-regarded original has been thoroughly revised by Drs. John M. Mathis, Hervé Deramond, and Stephen M. Belkoff to reflect recent advances in percutaneous vertebroplasty and kyphoplasty. Obsolete sections have been judiciously replaced with cutting-edge material, such as an in-depth look at the latest bone cements and devices. Chapters outline spine anatomy, medical management, and patient selection. The addition of practical and challenging case studies furthers the focus of the previous edition by bridging the gap between theory and practice for spine interventionalists, radiologists, neuroradiologists, orthopedic surgeons, and neurosurgeons. The text is enhanced by a wealth of illustrations. Featured in the Second Edition: * New data on alternate routes for therapy, sacroplasty, and treating tumors * New treatment techniques * Updated examination of biomechanics * New material on complications * New figures and color images * Inclusion of vertebroplasty and kyphoplasty cases * Expanded presentation of ACR and SIR care standards. © 2006, 2002 Springer Science+Business Media, Inc., All rights reserved.
The health industry collects huge amounts of health data, which, unfortunately, are not mined to discover
hidden information. Information technologies can provide alternative approaches to the diagnosis of the
osteoporosis disease. In this chapter, the authors examine the potential use of classification techniques
on a huge volume of healthcare data, particularly in anticipation of patients who may have osteoporosis
disease through a set of potential risk factors. An innovative solution approach based on dynamic reduced
sets of risk factors using the promising Rough Set theory is proposed. An experimentation of several
classification techniques have been performed leading to rank the suitable techniques. The reduction of
potential risk factors contributes to enumerate dynamically optimal subsets of the potential risk factors
of high interest leading to reduce the complexity of the classification problems. The performance of the
model is analyzed and evaluated based on a set of benchmark techniques.
Objectives
To determine whether the association between change in bone mass density (BMD) over 4 years and risk of hip and nonvertebral fracture differs according to an individual's history of falls.DesignPopulation-based cohort study.SettingFramingham, Massachusetts.ParticipantsIndividuals with two measures of BMD at the femoral neck (mean age 78.8; 310 male, 492 female).MeasurementsCox proportional hazards models were used to estimate hazard ratios (HRs) for the association between percentage change in BMD (per sex-specific standard deviation) and risk of incident hip and nonvertebral fracture. Models were stratified based on history of falls (≥1 falls in the past year) and recurrent falls (≥2 falls) ascertained at the time of the second BMD test. Interactions were tested by including the term “fall history * change in BMD” in the models.ResultsMean change in BMD was −0.6%/year; 27.8% of participants reported falls, and 10.8% reported recurrent falls. Seventy-six incident hip and 175 incident nonvertebral fractures occurred over a median follow-up of 9.0 years. There was no difference in the association between change in BMD and hip fracture according to history of falls (P for interaction = .57). The HR associated with change in BMD and nonvertebral fracture was 1.31 (95% confidence interval (CI) = 1.10–1.56) in participants without a history of falls and 0.95 (95% CI 0.70–1.28) in those with a fall (interaction P = .07). Results for recurrent fallers were similar.Conclusion
The effect of BMD loss on risk of nonvertebral fracture may be greater in persons without a history of falls. It is possible that change in BMD contributes less to fracture risk when a strong risk factor for fracture, such as falls, is present.
Osteoporosis (OP), the most frequent bone disease affecting the general population, is associated with high fracture risk. Patients with impaired kidney function have bone and mineral disturbances leading to extraskeletal calcifications and complex changes in bone turnover that predispose them to increased fracture risk accompanied by increased morbidity and mortality. The combination of these two bone disorders seems to have an additive effect with regard to fracture risk and its outcome, so that appropriate diagnosis and treatment of this disorder should be of primary concern when approaching patients with kidney disease. Nevertheless, the clinical and laboratory diagnostic tools used to identify OP in the general population do not suit the requirement for detecting the complex bone and metabolic changes that occur with chronic kidney disease, leading to the lack of or the initiation of inappropriate therapy. This review will focus on the bone pathophysiologic processes involved in OP and renal osteodystrophy and address some of the problems associated with our current diagnostic tools and aspects of the therapeutic approaches.
Longitudinal studies have shown that individuals lose bone mineral at unequal rates with aging. It has been postulated that individuals with the more rapid rates of loss constitute a separate population having an increased risk for developing fractures, i.e., osteoporosis. To examine this postulate, we made a search for a separate population of elderly women using a precise and objective measurement technique of bone mineral, photon absorptiometry. Bone mineral content (BMC) was measured in the radius of 571 Caucasian females who were age 50 or older. It was found that BMC values adjusted for width had a normal distribution in all decades and the variation in BMC values did not increase with age. Subjects with vertebral fractures (n = 108) were estimated to be losing bone mineral at the same rate as those without vertebral fractures (n= 161). Thus evidence for a separate population of rapid losers of bone mineral was not found. Reconciliation of longitudinal studies which show unequal rates of loss with the present population survey, in which evidence for unequal rates was not found, would require that (a) the rate of loss of bone mineral for an individual is not constant and/or (b) the rate of mineral loss is proportional to the amount of mineral present at maturity. The incidence of vertebral fractures was inversely proportional to BMC values. In a group of 278 women followed for 470 subject-yr, the incidence of all fractures during the study (n = 31) was also inversely proportional to BMC. These data suggest that the BMC values of osteoporotics would be at the lower end of normally distributed values for the population.
Quantitative polarised light microscopy was applied to sections of unfixed, undecalcified bone taken at operation from patients with two types of proximal femoral fracture, subcapital and trochanteric. Specimens were also taken from the equivalent sites in otherwise normal subjects at autopsy, and from various other sites of traumatic fractures; these two latter groups acted as controls. Analysis of the 57 specimens disclosed changes in the nature of the bone at the site of subcapital fractures, namely the presence of relatively large crystals of hydroxyapatite and a change in the molecular orientation, but not total content, of the acidic proteoglycans of the bone matrix. Our results have confirmed and extended the findings of others on subcapital fractures, and have also shown very similar changes in the trochanteric fractures. It thus appears that the bony changes in the two types of proximal femoral fracture are not as different as has been suggested.
We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures. The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged -0.31 (P < 0.05) for the femoral neck, -0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was -1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, "postmenopausal osteoporosis," is characterized by excessive and disproportionate trabecular bone loss, involves a small subset of women in the early postmenopausal period, and is associated mainly with vertebral fractures. The other form, "senile osteoporosis," is characterized by proportionate loss of both cortical and trabecular bone, involves essentially the entire population of aging women and, to a lesser extent, aging men, and is associated with hip fractures or vertebral fractures or both.
Newer radiologic techniques permit the measurement of spinal mineral content and are likely to be increasingly preferable to plain radiographs of the spine. Single-energy photon absorptiometry is inexpensive, but may not be applicable to the spine. Dual photon absorptiometry can be used to quantify changes in bone mineral content in patients who have metabolic bone disease or who are undergoing treatment that alters bone mineral content. Currently, computed tomography has the advantage of quantifying changes in the trabecular portion of the axial skeleton.
It has long been debated whether hip fractures are best thought of as disease, ie, osteoporosis, or accident. Most investigators believe that age-related bone loss accounts for the rise in hip fracture incidence among the elderly (Consensus Conference 1984), and it has even been suggested that, as a result of osteoporosis, hip fractures can occur without a fall (Reeves, 1977; Smith, 1953). Others claim that osteoporosis has little etiologic relationship to hip fracture risk (Aitken, 1984; Cummings, 1985; Evans et al, 1981; Wicks et al, 1982) and that other determinants such as risk factors for falls are all important (Aitken, 1984; Wicks et al, 1982). We believe, however, that both osteoporosis and trauma are important in the production of hip fractures and that neither alone can completely account for the rise in hip fracture incidence with age. This point of view is based on the evidence outlined below.
Three methods of carrying out a regression analysis of data collected by means of a survey of complex design are investigated. Least squares methods which ignore population structure such as clustering or stratification can give seriously misleading results. Probability weighted methods are much better and give reasonable inferences for equal probability designs. However, for designs with widely differing selection probabilities the inferences can be poor. The best results were obtained for an estimator derived from maximum likelihood theory. This estimator requires that values of a design variable be known for all units in the population. Some aspects of the robustness of this procedure are studied.
This article offers a practical guide to goodness-of-fit tests using statistics based on the empirical distribution function (EDF). Five of the leading statistics are examined—those often labelled D, W , V, U , A —and three important situations: where the hypothesized distribution F(x) is completely specified and where F(x) represents the normal or exponential distribution with one or more parameters to be estimated from the data. EDF statistics are easily calculated, and the tests require only one line of significance points for each situation. They are also shown to be competitive in terms of power.
The bone mineral content of the femoral neck of 61 autopsy specimens was assayed by x-ray spectrophotometry. The mechanical strength of the specimens was also determined experimentally by applying a compressive force perpendicularly to the shaft. The ultimate force at fracture was obtained from force/displacement plots. A coefficient of correlation of 0.89 between bone mineral content of the femoral neck and the ultimate force at fracture was found. Even when limited to a group of women aged 67-80 a fairly close correlation was found. This indicates that the bone mineral level, measured in vivo, can be used as a criterion of the risk of fracture in elderly women.
Relations between mineralisation and mechanical properties have been investigated in human femoral compacta. Evidence of age-related changes in physical properties of bone, independent of mineral density, is provided by significant (P < 0.05) partial correlation between ultimate tensile stress and age. However, 75 per cent of variance in ultimate tensile stress, and 85 per cent of variance in ultimate compressive stress could be accounted for by variation in mineral density. © 1976 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
The relation between pre-treatment blood-pressure and the fall in pressure after treatment was examined for most classes of antihypertensive drugs. Positive correlations were demonstrated for all drugs, for placebo, and for bed rest. This suggests that for all manoeuvres response is related to the height of the pretreatment pressure. Substitution of the pre-treatment and achieved pressures by random numbers reveals that positive correlations are mathematically inevitable and do not indicate any action on a basic mechanism of essential hypertension. After statistical correction for mathematical associations between the variables the apparent effects were generally lost. A correlation between the pre-treatment value of any variable and its change after a therapeutic intervention thus may not be valid.
The increasing availability of noninvasive methods for measuring bone mass raises the issue of whether perimenopausal women should routinely have such measurements to identify those at risk for osteoporotic fractures of the hip, wrist, and spine. Although the mortality and morbidity caused by hip fractures would warrant routine screening, measurement of bone mass has uncertain value in assessing the risk for hip fracture. Wrist fractures generally cause only transient disability, and measurement of bone mass may not reliably predict risk. Measurements of bone density of the spine might be better able to assess a woman's risk for vertebral fractures, but the value of screening depends on whether the findings would affect a woman's decision about using estrogen therapy after menopause. Serial measurements of bone mass to estimate a woman's rate of bone loss are relatively imprecise, increase the cost of screening, and have at best a limited role in screening women to assess risk for osteoporotic fractures.
Despite a general impression to the contrary, the risk factors for age-related fractures are poorly understood. There are indications, however, that these risk factors may vary from one skeletal site to another, depending on the pathophysiology of bone loss at the site and on the relative contributions of trauma and bone strength. Accurate knowledge of risk factors for specific fractures could help in the design of efficient screening and treatment programs for osteoporosis, while a clear understanding of fracture heterogeneity might lead to new hypotheses concerning etiology. However, a much more comprehensive approach to the study of the risk factors for age-related fractures will be necessary to achieve these ends.
Assessment of fracture threshold (FT) could have important clinical application in determining which individuals should be treated preventively, and what level of therapy to prescribe, if suitable treatment regimens can be developed. We propose that FT be defined as the bone mineral content (BMC) at which the risk of fracture doubles, relative to premenopausal women, as determined by logistic regression analysis of spine fracture incidence in a prospective study of 408 postmenopausal women. The observed values for the FT agree well with those reported by others, based upon more arbitrary definitions. More than 90% of individuals with new nonviolent spine fractures have BMC below the fracture threshold, while fewer than 10% of younger women (age 30-45) are below this value. Although not all women with BMC below the FT have had fractures, they are at increased risk of fracture. Women with BMC equivalent to the FT have at least a 5% chance of fracture over a 10-year period, and the probability of fracture rises rapidly as BMC decreases. BMC appears to be a much stronger predictor of fracture risk than age or body size (height or weight). Thus, use of a BMC fracture threshold to categorize individual risk could provide a more objective basis for clinical decision making.
Rapid loss of trabecular bone (as after menopause) occurs by complete removal of some structural elements, leaving those that remain more widely separated and less well connected. The most likely cellular mechanism is an increase in the number of resorption cavities deep enough to lead to focal perforation of trabecular plates, either as a non-specific consequence of increased remodeling activation, or as a specific consequence (direct or indirect) of estrogen deficiency. Disruption of the connections between structural elements produces a disproportionate loss of strength, for which the increased thickness of the remaining trabeculae can only partly compensate. Consequently, the most biomechanically significant component of trabecular bone loss occurs rapidly and irreversibly. This emphasizes the importance of prevention, but no treatment except estrogen replacement is of proven efficacy in preventing estrogen-dependent bone loss. For adequate repair of structural damage after it has been allowed to occur, adding bone to existing surfaces may be insufficient, and it may be necessary to devise some means of forming new bone directly in the bone marrow cavity in order to re-establish normal connectivity.
The incidence of cervical and intertrochanteric proximal femur fractures at various levels of cervical and intertrochanteric bone mineral density, respectively, was estimated by using population-based data from ongoing studies of osteoporosis and fractures among women residing in Rochester, Minnesota. Hip fractures were uncommon among women with femoral bone density greater than or equal to 1.0 g/cm2, but their frequency increased as bone density declined below that point at both femoral sites. The incidence of cervical femur fractures was estimated at 8.3 per 1,000 person-years among women with cervical bone density less than 0.6 g/cm2, while the estimated incidence of intertrochanteric femur fractures reached 16.6 per 1,000 person-years among those with intertrochanteric bone density less than 0.6 g/cm2. This new approach to the assessment of fracture risk from bone mineral density measurements indicates that osteoporosis is an important underlying cause of hip fractures.
Osteoporosis and associated fractures are common in Western countries, especially among elderly white women. In the United States alone, the total cost of osteoporosis and osteoporotic fractures was estimated to be 6.1 billion dollars in 1983. In addition to enormous economic costs, these fractures cause considerable disability and many premature deaths. As the number of elderly increases, so will the magnitude of the problem. Consequently, the public, health professionals, and policymakers have become increasingly concerned about prevention of osteoporosis and osteoporotic fractures. Osteoporosis may be defined as a reduction in bone mass that increases susceptibility to fracture. Defining osteoporosis more precisely is difficult since, for a specific age and sex, there is a wide, continuously distributed range of bone mass and no distinctly separate group of people with low bone mass. Average bone mass tends to decrease after the fourth or fifth decade in all populations studied so far, so that bone loss may be considered an almost universal phenomenon of aging. Osteoporosis predisposes to fractures of the hip, vertebrae, distal forearm, humerus, pelvis, and other, less common types of fractures. With sufficient force of injury, these fractures can occur in anoyone, but they are considered to be 'osteoporotic' when they occur in the elderly or as the result of minimal trauma (no more severe than that resulting from falling from a standing height).
In a study of 1098 women (mean age, 63.3 years) nonspine fracture incidence and prevalence rates and spine fracture prevalence rates were compared by quintile of bone mineral content at the proximal radius, distal radius, os calcis, and lumbar spine. The risk of fracture associated with varying bone mineral content levels was explored with use of estimated odds ratios. Risk of fracture is significantly increased with diminishing quintiles of bone mineral content. Subjects in the lowest quintile of os calcis bone mineral content have a nonspine fracture risk 10 times greater than subjects in the highest bone mineral content quintile. The os calcis bone mineral content measurement is the best predictor of nonspine fracture risk and is also the best overall indicator of spine fracture risk. Therefore measurement of os calcis bone mineral content may be useful for routine risk evaluation of perimenopausal women. The ability to predict individual risk should allow for more rational preventive regimens.
Thirty three fresh femora from 18 cadavera were loaded to fracture at a deformation rate of 5 mm/min to study the effect of density of the cancellous core in fracture initiation of the femoral neck. The neck of the femur was modelled as a composite beam subjected to bending and the ultimate strength of the bone at the superior aspect of the neck was calculated from the model, which was fed by the mechanical tests and geometry measurements. The area porosity of the cancellous core was introduced into the beam model after measuring the apparent density of dry fat-free bone for each specimen. The results showed a strong dependence between the ultimate strength obtained and the cancellous bone density, the latter previously measured for each specimen by the non-invasive Compton scattering technique. Area porosity of the femoral neck was found to have little effect on the results obtained, permitting the use of an average value for this parameter in calculating the ultimate strength of the neck of the femur.
The bone density, mineral content and average shear stress in bending at failure were measured in vitro in 33 femoral necks of women and men of different ages. The correlations between these three parameters as well as their correlation with the Singh index were carefully analyzed and found to show that the Singh index is of no clinical value. The best correlation exists between bone density and shear stress at failure. Practically no correlation is found between the breaking stress and Singh index. The breaking stress decreases with age much faster than the bone density or bone mineral content. The correlation between the work to fracture and the bone density or its mineral content is only moderate. The bone density is best indicator for the compressive bone strength. The changes of bone strength are apparently influenced by factors other than the bone density and mineral content, although the possibility that small changes in bone density or mineral content cause large changes in bone strength cannot be excluded.
During the 50-year period 1928 to 1977, 1,250 Rochester, Minnesota residents experienced 1,355 proximal femur (hip) fractures. The incidence of these fractures appeared to rise during the first 15 years of the study, but this was most likely due to underascertainment of cases in the early period since there was no evidence of a cohort effect. From 1943 onward, there was no significant increase in the incidence rates which remained relatively level for total hip fractures, initial hip fractures alone, and for initial hip fractures due to moderate trauma. Thus, we found no evidence to support the contention that hip fracture incidence has risen dramatically in recent years. Secular changes in incidence cannot account for the observation that hip fracture rates in Rochester are greater than those reported from earlier population-based studies.
A survey was done of aging changes in compact and trabecular bone. During the past decade, noninvasive methods have demonstrated similar results for compact bone in large samples. Aging decreases of 3%/decade begin at about age 40 in both sexes and continue, but in women, an additional loss occurs after menopause, bringing their total rate of decrease to 9%/decade between ages 45 and 75. Results on trabecular bone loss are more variable, the majority indicating a slightly lower rate of loss (6% to 8% decade), beginning in young adulthood (20 to 40 years) in both sexes. These findings suggest that the common assumption about a large ongoing loss of trabecular bone after menopause may be erroneous. These assumptions are examined, as are the implications of the findings for calcium metabolism, anatomical correlations and fracture incidences.
In a large population-based study of hip fracture recurrence in Rochester, Minnesota, the overall risk of any recurrence, ipsilateral or contralateral, was estimated to be 29% by 20 years after initial fracture, 1.6 times greater than expected. The risk of recurrence was greater in patients who had initial fractures associated with moderate trauma and in younger patients. The increased risk among women compared to men was eliminated when the degree of trauma was considered. Ipsilateral recurrence at the same fracture site was less frequent than expected, and the overall increased risk was primarily due to contralateral fractures at the initial fracture site (cervical or intertrochanteric). There was no difference in recurrence rate with respect to site or side of the initial fracture, and no concentration of recurrences was observed for any particular time interval following the first hip fracture.
A review of the literature on the epidemiology of hip fractures demonstates the predominance of females. Women comprise 70 to 80% of patients with hip fractures. The average age is generally in the eighth decade. Actual incidence rates vary from one study to another, with lower rates among blacks and apparently lower rates from tropical countries. Osteoporosis is more common among patients with hip fractures than in controls and is somewhat more common in intertrochanteric fractures than in femoral neck fractures. Most hip fractures result from comparatively minor falls, such as falls from a bed, a chair, or from a standing position, especially among the elderly. It is estimated that more than 200,000 hip fractures occur each year in the United States, and that the cost of caring for these patients is more than $750,000,000. Approximately 19% of these patients die as a result of the fracture. This contributes significantly to the total number of accidental deaths, which in turn is the fourth largest category in the list of causes of death in the United States.
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- Smith D.M.
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Radiologic methods to evaluate bone mineral content
- Kimmel