Evaluation Of Fracture Risk Research Articles

A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries.

Some conditions are already known to be associated with an increased risk of osteoporotic fractures. Other conditions may also be significant indicators of increased risk. The aim of the current study was to identify conditions for inclusion in a fracture prediction model (fracture risk evaluation model [FREM]) for automated case finding of high-risk individuals of hip or major osteoporotic fractures (MOFs). We included the total population of Denmark aged 45+ years (N = 2,495,339). All hospital diagnoses from 1998 to 2012 were used as possible conditions; the primary outcome was MOFs during 2013. Our cohort was split randomly 50/50 into a development and a validation dataset for deriving and validating the predictive model. We applied backward selection on ICD-10 codes (International Classification of Diseases and Related Health Problems, 10th Revision) by logistic regression to develop an age-adjusted and sex-stratified model. The FREM for MOFs included 38 and 43 risk factors for women and men, respectively. Testing FREM for MOFs in the validation cohort showed good accuracy; it produced receiver-operating characteristic (ROC) curves with an area under the ROC curve (AUC) of 0.750 (95% CI, 0.741 to 0.795) and 0.752 (95% CI, 0.743 to 0.761) for women and men, respectively. The FREM for hip fractures included 32 risk factors for both genders and showed an even higher accuracy in the validation cohort as AUCs of 0.874 (95% CI, 0.869 to 0.879) and 0.851 (95% CI, 0.841 to 0.861) for women and men were found, respectively. We have developed and tested a prediction model (FREM) for identifying men and women at high risk of MOFs or hip fractures by using solely existing administrative data. The FREM could be employed either at the point of care integrated into electronic patient record systems to alert physicians or deployed centrally in a national case-finding strategy where patients at high fracture risk could be invited to a focused DXA program. © 2018 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

3-D Subject-Specific Shape and Density Estimation of the Lumbar Spine From a Single Anteroposterior DXA Image Including Assessment of Cortical and Trabecular Bone.

Dual Energy X-ray Absorptiometry (DXA) is the standard exam for osteoporosis diagnosis and fracture risk evaluation at the spine. However, numerous patients with bone fragility are not diagnosed as such. In fact, standard analysis of DXA images does not differentiate between trabecular and cortical bone; neither specifically assess of the bone density in the vertebral body, which is where most of the osteoporotic fractures occur. Quantitative computed tomography (QCT) is an alternative technique that overcomes limitations of DXA-based diagnosis. However, due to the high cost and radiation dose, QCT is not used for osteoporosis management. We propose a method that provides a 3-D subject-specific shape and density estimation of the lumbar spine from a single anteroposterior (AP) DXA image. A 3-D statistical shape and density model is built, using a training set of QCT scans, and registered onto the AP DXA image so that its projection matches it. Cortical and trabecular bone compartments are segmented using a model-based algorithm. Clinical measurements are performed at different bone compartments. Accuracy was evaluated by comparing DXA-derived to QCT-derived 3-D measurements for a validation set of 180 subjects. The shape accuracy was 1.51 mm at the total vertebra and 0.66 mm at the vertebral body. Correlation coefficients between DXA and QCT-derived measurements ranged from 0.81 to 0.97. The method proposed offers an insightful 3-D analysis of the lumbar spine, which could potentially improve osteoporosis and fracture risk assessment in patients who had an AP DXA scan of the lumbar spine without any additional examination.

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings.

EAA clinical guideline on management of bone health in the andrological outpatient clinic.

Male osteoporosis is now a well-recognized medical disorder with established clinical guidelines for both diagnosis and management. Prevention as well as management of osteoporosis in men consulting the andrological outpatient clinic because of low testosterone, however, is not well established. This gap of knowledge is-at least partly-explained by the controversy with respect to the threshold of testosterone needed for skeletal maintenance. However, testosterone deficiency may be clearly associated with bone loss as well as frailty in men. If anything, andrologists should therefore be aware of the potential silent presence of osteoporosis in men with confirmed hypogonadism. Therefore, the management of patients with potential hypogonadism should include a complete bone health assessment, besides clinical and biochemical evaluation of gonadal status. Such bone health assessment should include specific items in medical history and physical examination related to fracture risk. Furthermore, dual-energy absorptiometry is indicated to evaluate fracture risk in men with confirmed clinical hypogonadism. Regarding treatment, besides general measures to prevent or manage male osteoporosis testosterone replacement can be initiated (as described in guidelines for hypogonadism), but data on its efficacy in preventing fractures are lacking. Thus, additional anti-osteoporotic may be needed, especially in men with very low testosterone who are at high risk of bone loss and/or in men not able to receive testosterone replacement.

Accumulation of carboxymethyl-lysine (CML) in human cortical bone.

Advanced glycation end-products (AGEs) are a category of post translational modification associated with the degradation of the structural properties of multiple different types of tissues. Typically, AGEs are the result of a series of post-translational modification reactions between sugars and proteins through a process known as non-enzymatic glycation (NEG). Increases in the rate of NEG of bone tissue are associated with type 2 diabetes and skeletal fragility. Current methods of assessing NEG and its impact on bone fracture risk involve measurement of pentosidine or total fluorescent AGEs (fAGEs). However, pentosidine represents only a small fraction of possible fAGEs present in bone, and neither pentosidine nor total fAGE measurement accounts for non-fluorescent AGEs, which are known to form in significant amounts in skin and other collagenous tissues. Carboxymethyl-lysine (CML) is a non-fluorescent AGE that is often measured and has been shown to accumulate in tissues such as skin, heart, arteries, and intervertebral disks, but is currently not assessed in bone. Here we show the localization of CML to collagen I using mass spectrometry for the first time in human bone. We then present a new method using demineralization followed by heating and trypsin digestion to measure CML content in human bone and demonstrate that CML in bone is 40-100 times greater than pentosidine (the current most commonly used marker of AGEs in bone). We then establish the viability of CML as a measurable AGE in bone by showing that levels of CML, obtained from bone using this technique, increase with age (p<0.05) and are correlated with previously reported measures of bone toughness. Thus, CML is a viable non-fluorescent AGE target to assess AGE accumulation and fragility in bone. The method developed here to extract and measure CML from human bone could facilitate the development of a new diagnostic assay to evaluate fracture risk and potentially lead to new therapeutic approaches to address bone fragility.

The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study.

The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures.This retrospective observational study was conducted from January to June 2015 at the Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda, Milan, Italy. An Italian population of 125 consecutive postmenopausal women was investigated for bone quantity and bone quality. Patients with neurological diseases regarding balance and vestibular dysfunction, sarcopenia, past or current history of diseases and use of drugs known to affect bone metabolism were excluded. Dual X-ray absorptiometry was used to assess bone quantity (bone mineral density) and bone quality (trabecular bone score and bone strain). Biochemical markers of bone turnover (type I collagen carboxy-terminal telopeptide, alkaline phosphatase, vitamin D) have been measured. Morphometric fractures have been searched by spine radiography. Balance was evaluated by the Romberg test. The data were evaluated with the neural network analysis using the Auto Contractive Map algorithm. The resulting semantic map shows the Minimal Spanning Tree and the Maximally Regular Graph of the interrelations between bone status parameters, balance conditions and fractures of the studied population. A low fracture risk seems to be related to a low carboxy-terminal cross-linking telopeptide of type I collagen level, whereas a positive Romberg test, together with compromised bone trabecular microarchitecture DXA parameters, appears to be strictly connected with fragility fractures. A simple assessment of the risk of fragility fracture is proposed in order to identify those frail patients at risk for osteoporotic fractures, who may have the best benefit from a pharmacological and physiotherapeutic approach.

The assessment of Trabecular bone score to improve the sensitivity of FRAX in patients with type 2 diabetes mellitus

Aim. To estimate the trabecular bone score (TBS) for evaluation of fracture probability in order to make decisions about starting osteoporosis treatment in patients with type 2 diabetes mellitus (T2DM).&#x0D; Materials and methods. We obtained the bone mineral density (BMD) and trabecular bone score (TBS) using dual energy X-ray absorptiometry (iDXA) in patients with T2DM (with and without a history of osteoporotic fractures) versus the control group. Before and after TBS measurements we assessed the ten-year probability of fracture using the Fracture Risk Assessment Tool (FRAX).&#x0D; Results. We enrolled 48 patients with T2DM, including 17 with a history of low-traumatic fracture, 31 patients without fractures and 29 subjects of a control group. BMD was higher in patients with T2DM compared to the control group at L1L4 (mean T-score 0.44, 95% CI -3.2 4.9 vs mean T-score 0.33, 95% CI -2.9 3.0 in a control group p=0.052) and Total Hip (mean T-score 0.51, 95% CI -2.1 3.0 vs mean T-score -0.03, 95% CI -1.4 1.2 in a control group p=0,025). The TBS and 10-year probability of fracture (FRAX) was not different in patients with T2DM versus the control group. However, when the TBS was entered as an additional risk factor, the 10-year probability of fracture became higher in patients with T2DM (10-year probability of fracture in T2DM- 8.68, 95% CI 0.3-25.0 versus 6.68, 95% CI 0.415.0 in control group, p=0.04). Among patients with diabetes with and without fractures the FRAX score was higher in subjects with fractures, but no difference was found in regards to BMD or TBS. Entering BMD and TBS values into the FRAX tool in subjects with diabetes and fractures decreased the FRAX score. However, patients with low-traumatic fractures should be treated for osteoporosis without a BMD, TBS or FRAX assessment.&#x0D; Conclusion. TBS improves the results of FRAX assessment in patients with T2DM and should be entered while evaluating FRAX in patients with T2DM. However, additional research is needed to develop a more sensitive tool to evaluate fracture risk in patients with T2DM.

Population study evaluating fracture risk among patients with chronic osteomyelitis.

BackgroundStudies investigating the fracture risk in patients with chronic osteomyelitis (COM) limited to case reports. This study evaluated the association between COM and subsequent fracture risk using population-based data.MethodsA subset claims data of the Taiwan National Health Insurance was used to identify 7,147 patients with COM newly diagnosed in 1999–2005 without fracture history and 28,588 general population controls, frequency matched by sex, age and diagnosis date. The incident fractures was measured by the end of 2013.ResultsThe incidence density of fracture was 1.94-fold greater in the COM cohort than in controls (21.5 vs. 11.1 per 1000 person-years), with the adjusted hazard ratio (HR) of 1.81 (95% CI: 1.67–1.95) for COM patients compared to controls after controlling for sex, age, and comorbidities of diabetes, osteoporosis, depression and end-stage renal disease in Cox proportional hazards regression. The fracture risk increased with age and women were at greater risk than men. The fracture incidence increased substantially in those with osteoporosis, 40.2 per 1000 person-years in COM patients. Site specific analysis showed a higher portion of incident fractures for lower limbs, 52.7% in COM cohort and 46.3% in controls.ConclusionFindings in this 15-year follow-up observation support our hypothesis that patients with COM are at an elevated risk of subsequent fracture. COM patients and the elderly deserve adequate consultation and awareness for fracture prevention.

Risk and adverse outcomes of fractures in patients with liver cirrhosis: two nationwide retrospective cohort studies

ObjectiveThe aim of this study is to evaluate fracture risk and post-fracture outcomes in patients with and without liver cirrhosis (LC).DesignRetrospective cohort study and nested fracture cohort study.SettingThis study was...

Spontaneous osteoclastogenesis: Hypothesis for gender-unrelated osteoporosis screening and diagnosis

Women are at greater risk of developing osteoporosis (OP). However, in the past few years it has become more widely recognized that OP is a significant problem also in men although OP is frequently under-diagnosed and, consequently, under treated in men. Most guidelines, screening and fracture risk evaluation methods as well as pharmacologic agents have been developed for women and then adapted to men. Bone Mineral Density (BMD) measurement by Dual X-ray Absorptiometry (DEXA) is reported as T score and the capability of DEXA to diagnose OP and predict fracture risk is still debated. In addition, the use of female T score references for the diagnosis of OP in men is incorrect for the following reasons: 1) DXA definition was developed just for Caucasian women, 2) men and women display structural differences in terms of bone growth, catabolism and size; 3) aging men have more periosteal apposition, less cortical porosity and endocortical resorption than aging women; and 4) T scores results, both in man and in women, can be affected by the presence of co-morbidities and it is known that in men OP is often secondary.From a biological point of view, OP is mainly due to increased osteoclastic activity leading to an imbalance in bone remodeling that favors resorption. However, some evidence suggests a more complex identity for osteoclasts (OCs) over and above their simple role of ‘bone eaters’. In our laboratory, we observed spontaneous OCs formation in vitro in peripheral blood mononuclear cells (PBMC) from OP patients (n.12 female patients and n.6 male patients; DXA T score-2.5 or less). Some researchers demonstrated OCs gender differences in bone resorption activity of female-derived versus male-derived OCs. Indeed, further data from our laboratory also showed gender differences in number of spontaneously differentiated OCs and differentiation time. Therefore, we hypothesized that it would be possible to perform OP screening and diagnosis observing and measuring PBMCs different ability to differentiate spontaneously into OCs in male and female patients. If this hypothesis will be confirmed, it will result in an effective and efficient strategy for OP screening, diagnosis, monitoring and fracture prevention, targeting health service resources on selected patients. However, our hypothesis must be tested in a properly designed clinical trial and several key issues still need to be addressed.

The use of bone mineral density measured by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed microtomography in chronic kidney disease.

Chronic kidney disease (CKD) is a risk factor for fractures. The current evaluation of fracture risk is based upon the combination of various clinical factors and quantitative imaging of bone. X-ray-based tools were developed to evaluate bone status and predict fracture risk. Dual energy X-ray absorptiometry (DXA) is available worldwide. Longitudinal studies showed that low areal Bone Mineral Density (BMD) measured by DXA predicts fractures in the CKD population as it does in non uremic populations, with good specificity and moderate sensitivity. Peripheral quantitative computed tomography (pQCT) and high resolution pQCT are research tools which measure volumetric BMD at the tibia and radius. They are able to discriminate between the cortical and trabecular envelopes which are differentially affected by renal osteodystrophy. In CKD, a rapid thinning and increased porosity at the cortex is observed which is associated with increased the risk for fracture.

Risk and outcomes of fracture in peripheral arterial disease patients: two nationwide cohort studies.

Limited information was available on the association between PAD and fracture. The purpose of this study is to evaluate fracture risk and post-fracture outcomes in patients with PAD. We identified 6647 adults aged ≥20years with newly diagnosed PAD using the Taiwan National Health Insurance Research Database in 2000-2004. Comparison cohort consisted of 26,588 adults without PAD randomly selected with frequency matching in age and sex. Events of fracture were identified during the follow-up period from January 1, 2000 until December 31, 2013, to evaluate adjusted hazard ratios (HR) and 95% confidence interval (CI) of fracture associated with PAD. Another nested cohort study of 799,463 hospitalized fracture patients analyzed adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture among patients with and without PAD in 2004-2013. Incidences of fracture in people with and without PAD were 22.1 and 15.5 per 1000 person-years, respectively (P<.0001). Compared with control, the adjusted HR of fracture was 1.59 (95% CI, 1.48-1.69) for PAD patients. In the nested cohort study, patients with PAD had higher post-fracture mortality (OR=1.16; 95% CI, 1.09-1.25) and various complications. PAD patients also had comparatively higher medical expenditure (2691 vs. 2232 USD, P<.0001) and longer hospital stay (10.6 vs. 9.0days, P<0.0001) during fracture admission. Increased risk of fracture and post-fracture adverse outcomes were associated with PAD. This susceptible population needs care to prevent fracture and to minimize adverse outcomes after it occurs.

Fracture Risk Assessment Tool (FRAX®) Results Calculated With and Without Bone Mineral Density Values for the Evaluation of Fracture Risk in Postmenopausal Women With Osteopenia

The aim of this study was to evaluate the agreement between fracture risk predictions based on calculations made with and without bone mineral density (BMD) values using the Fracture Risk Assessment Tool (FRAX®) in Turkish postmenopausal women with osteopenia and to compare the treatment recommendations. This descriptive, cross-sectional study included postmenopausal women aged 50–79 yr with a diagnosis of osteoporosis who were not receiving any treatment. A questionnaire was administered to the participants face-to-face to obtain sociodemographic characteristics, medical history, and fracture history. Fracture risk was calculated with FRAX® separately with and without BMD. The study included 230 postmenopausal patients with osteopenia. The mean age of the patients was determined as 63.16 ± 7.59 yr, and the mean body mass index was 30.61 ± 5.02. The intraclass correlation coefficient values of the 10-yr major osteoporotic (MO) fracture and hip fracture score agreement with FRAX® with and without BMD were mean 0.486 and 0.462, respectively. The risk of MO fracture with an intervention threshold of ≥20 was determined in 227/230 patients (98.7%), and the risk of hip fracture with treatment recommendations of ≥3 was determined in 204/230 patients (88.7%). Treatment recommendations in patients with no fracture history and secondary osteoporosis were 100% for MO fracture and 94.7% (123/130) for hip fracture risk. The treatment recommendation rates of FRAX® with and without BMD were similar for the majority of postmenopausal women with osteopenia. The agreement between the values was of a moderate level. When patients with a fracture history and secondary osteoporosis were excluded, the agreement increased. Even though values with BMD are of basic importance for medical treatment in postmenopausal women, the use of measurements evaluating fracture risk, such as FRAX® without BMD, could be useful in postmenopausal women with osteopenia.

Methodology to Produce Specimen-Specific Models of Vertebrae: Application to Different Species

Image-based continuum-level finite element models have been used for bones to evaluate fracture risk and the biomechanical effects of diseases and therapies, capturing both the geometry and tissue mechanical properties. Although models of vertebrae of various species have been developed, an inter-species comparison has not yet been investigated. The purpose of this study was to derive species-specific modelling methods and compare the accuracy of image-based finite element models of vertebrae across species. Vertebral specimens were harvested from porcine (N = 12), ovine (N = 13) and bovine (N = 14) spines. The specimens were experimentally loaded to failure and apparent stiffness values were derived. Image-based finite element models were generated reproducing the experimental protocol. A linear relationship between the element grayscale and elastic modulus was calibrated for each species matching in vitro and in silico stiffness values, and validated on independent sets of models. The accuracy of these relationships were compared across species. Experimental stiffness values were significantly different across species and specimen-specific models required species-specific linear relationship between image grayscale and elastic modulus. A good agreement between in vitro and in silico values was achieved for all species, reinforcing the generality of the developed methodology.

Older Age and Higher Body Mass Index Are Associated With a More Degraded Trabecular Bone Score Compared to Bone Mineral Density

Trabecular bone score (TBS) may detect subjects with a more degraded microarchitecture but whose bone mineral density (BMD) reflects normal or osteopenia. The purpose of this study was to evaluate whether age and body sizes were associated with the discordance between BMD and TBS. We analyzed BMD and TBS in 1505 Korean women over 40 yr of age who had no history of osteoporotic fractures or conditions that affect bone metabolism. We considered 3 groups to have TBS values that reflected a more degraded TBS than their BMD values: (1) normal BMD but partially degraded TBS, (2) normal BMD but degraded TBS, and (3) osteopenia but degraded TBS. We compared subjects in these 3 groups with other subjects in terms of age and body sizes, and used multivariable logistic regression to analyze the odds ratios (ORs) for the occurrence of a more degraded TBS than their BMD level using age and body mass index (BMI). One hundred sixty subjects (10.6%) were found to have a more degraded TBS than their BMD level; these subjects were older, heavier, and had higher BMIs than the other subjects. Age (OR: 1.038, 95% confidence interval: 1.020–1.057, p< 0.001) and BMI (OR: 1.223, 95% confidence interval: 1.166–1.283, p< 0.001) were statistically significant in the multivariable analysis for the occurrence of this feature. Women with a more degraded TBS than their BMD level are older and have higher BMIs than the other subjects. It may be helpful to consider the possibility of trabecular bone degradation when clinically evaluating fracture risk in patients who are older or who have high BMIs with normal BMD or osteopenia.

Clavicle Fracture after Coracoclavicular Ligament Reconstruction: A Biomechanical and Finite Element Evaluation of Clavicle Fracture Risk

Objectives:Biomechanical testing supports anatomic reconstruction for high-grade acromioclavicular injuries to achieve improved stability, however, clavicle fractures have been reported following reconstruction. Thus, this study used laboratory experiments and finite element models to investigate the influence of tunnel parameters on the clavicle biomechanical performance.Methods:Composite synthetic clavicles were subjected to four-point bending on a servohydraulic load frame. Two established surgical techniques were compared; a single 3 mm tunnel technique and a double 6 mm tunnel technique. Finite element (FE) models were validated against experimental findings. Subsequent FE models explored a broad range of tunnel parameters to determine their biomechanical consequences.Results:The single tunnel (3 mm) specimens exhibited a stiffness of 19.9 ± 1.55 Nm2 and failed at 686 ± 45.2 N through the tunnel. The double tunnel technique exhibited a stiffness of 15.8 ± 1.18 Nm2 and failed at 390 ± 31.7 N through the medial tunnel. In FE models of the experiments (Fig. 1), the double tunnel technique has 69% of the strength of the single tunnel (vs 57% in the experiments) and failure was predicted at the medial tunnel. In 200 variations of tunnel configuration, the double tunnel technique exhibited increased stress concentration relative to a single tunnel. Larger tunnels exhibited higher stresses than smaller tunnels. Fig. 1: FE models exhibit greater stress concentration of the double 6 mm tunnel (right) technique compared to the single 3 mm tunnel (left) and technique.Conclusion:Experimental and FE results demonstrate that the double 6 mm tunnel reconstruction has a higher stress concentration than the single 3 mm tunnel technique when subjected to four-point bending. The validated FE model supports the use of small tunnels and suggests that a double tunnel configuration may have biomechanical disadvantages that must be weighed against the perceived advantages of “anatomic” reconstruction.

Response to "Clinical Evaluation of Bone Strength and Fracture Risk".

We read with great interest the recent review by de Bakker et al that summarized the state of several existing and emerging technologies for estimating bone strength and fracture risk in vivo. Much of their review focused on how well the measurements of selected technologies predicted experimental measurements of bone strength by ex vivo quasistatic mechanical testing (QMT) and on how well they tracked changes in mechanical properties of bone. The authors noted that the association of many common skeletal health measurements (e.g., DXA measures of trabecular bone score and areal and volumetric BMD) are only moderately associated with bone strength. The authors did not include mechanical response tissue analysis (MRTA) in their review. MRTA is a dynamic mechanical bending test that uses a vibration analysis technique to make immediate, direct, functional measurements of the mechanical properties (mass, stiffness, and damping) of long bones in humans in vivo. In this article we note our interest in the ability of MRTA to detect large changes in bone stiffness that go undetected by DXA. We also highlight results of our proprietary improvements to MRTA technology that have resulted in unmatched accuracy in QMT-validated measurements of the bending stiffness and estimates of the bending strength (both R2 = 0.99) of human ulna bones. To distinguish our improved technique from the legacy MRTA technology, we refer to it as Cortical Bone Mechanics Technology (CBMT). Further research will determine whether such CBMT measurements are clinically useful.

Evaluation of circulating sRAGE in osteoporosis according to BMI, adipokines and fracture risk: a pilot observational study

BackgroundOsteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism.ResultsCirculating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism.ConclusionsThe measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.

Evaluation of fracture risk in chronic kidney disease.

Chronic kidney disease (CKD) is associated with mineral and bone disorders (MBD) that are now considered as a syndrome. Bone fragility and a four to tenfold increased rate of skeletal fractures are often reported in CKD patients. The evaluation of the risk of these fractures in CKD patients should explore the same risk factors identified for the general population including low body weight, menopause, personal and familial history of osteoporosis, chronic inflammatory diseases, and corticosteroid therapy. The aim of this article is to provide a critical review of the tools used for the evaluation of bone loss and the risk of fracture in CKD patients, ranging from the measurement of bone mineral density (BMD), fracture risk assessment (Frax™), quantitative computed tomography (QCT), high-resolution peripheral quantitative computed tomography (HRpQTC), to circulating biomarkers of bone metabolism including vitamin D, parathyroid hormone (PTH), bone-specific alkaline phosphatase, osteocalcin, and some collagen type 1-related molecules indicators of bone remodeling.

Clinical Evaluation of Bone Strength and Fracture Risk.

This paper seeks to evaluate and compare recent advances in the clinical assessment of the changes in bone mechanical properties that take place as a result of osteoporosis and other metabolic bone diseases and their treatments. In addition to the standard of DXA-based areal bone mineral density (aBMD), a variety of methods, including imaging-based structural measurements, finite element analysis (FEA)-based techniques, and alternate methods including ultrasound, bone biopsy, reference point indentation, and statistical shape and density modeling, have been developed which allow for reliable prediction of bone strength and fracture risk. These methods have also shown promise in the evaluation of treatment-induced changes in bone mechanical properties. Continued technological advances allowing for increasingly high-resolution imaging with low radiation dose, together with the expanding adoption of DXA-based predictions of bone structure and mechanics, as well as the increasing awareness of the importance of bone material properties in determining whole-bone mechanics, lead us to anticipate substantial future advances in this field.