Changes in Cross-Sectional Area of Spinal Canal and Vertebral Body Under 2 Years of Teriparatide Treatment: Results from the EUROFORS Study

The treatment of osteoporotic patients with teriparatide is associated with a significant increase in bone formation and gain of bone mass. The purpose of this post hoc analysis was to determine if the cross-sectional area (CSA) of the spinal canal and the vertebral body is affected by teriparatide treatment. Narrowing of the spinal canal might represent a safety problem, while widening of the vertebral CSA might improve mechanical stability. High-resolution computed tomography (HRCT) scans of vertebra T12 were obtained at baseline and after 6, 12, and 24 months of teriparatide treatment (20 μg/day) from 44 postmenopausal women with established osteoporosis participating in the prospective, randomized EUROFORS study. The CSA of the spinal canal did not decrease but increased marginally by 0.9% (2.6 mm2) over 24 months (P < 0.001), with a range from −0.5% (−2 mm2) to 3.1% (+8 mm2). Even when analyzing the spinal CSA on a slice-by-slice basis, no clinically relevant narrowing of the spinal canal was observed. For vertebral bodies, the CSA increased by 0.7% (5.7 mm2) over 24 months (P < 0.001), with a range from −0.4% (–3 mm2) to 1.6% (+14 mm2). Our data do not provide evidence for safety concerns regarding spinal canal narrowing. On the other hand, the increases observed for vertebral CSA apparently also only minimally contribute to the mechanical strengthening of the vertebral body under teriparatide treatment

Opportunistic hip fracture risk prediction in Men from X-ray: Findings from the Osteoporosis in Men (MrOS) Study

Osteoporosis is a common disease that increases fracture risk. Hip fractures, especially in elderly people, lead to increased morbidity, decreased quality of life and increased mortality. Being a silent disease before fracture, osteoporosis often remains undiagnosed and untreated. Areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) is the gold-standard method for osteoporosis diagnosis and hence also for future fracture prediction (prognostic). However, the required special equipment is not broadly available everywhere, in particular not to patients in developing countries. We propose a deep learning classification model (FORM) that can directly predict hip fracture risk from either plain radiographs (X-ray) or 2D projection images of computed tomography (CT) data. Our method is fully automated and therefore well suited for opportunistic screening settings, identifying high risk patients in a broader population without additional screening. FORM was trained and evaluated on X-rays and CT projections from the Osteoporosis in Men (MrOS) study. 3108 X-rays (89 incident hip fractures) or 2150 CTs (80 incident hip fractures) with a 80/20 split were used. We show that FORM can correctly predict the 10-year hip fracture risk with a validation AUC of 81.44 +- 3.11% / 81.04 +- 5.54% (mean +- STD) including additional information like age, BMI, fall history and health background across a 5-fold cross validation on the X-ray and CT cohort, respectively. Our approach significantly (p < 0.01) outperforms previous methods like Cox Proportional-Hazards Model and \frax with 70.19 +- 6.58 and 74.72 +- 7.21 respectively on the X-ray cohort. Our model outperform on both cohorts hip aBMD based predictions. We are confident that FORM can contribute on improving osteoporosis diagnosis at an early stage.Comment: Accepted at MICCAI 2022 Workshop (PRIME

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Tree-structured subgroup analysis of receiver operating characteristic curves for diagnostic tests

Rationale and Objectives Multiple diagnostic tests are often available for a disease. Their diagnostic accuracy may depend on the characteristics of testing subjects. The investigators propose a new tree-structured data-mining method that identifies subgroups and their corresponding diagnostic tests to achieve the maximum area under the receiver-operating characteristic curve. Materials and Methods The Osteoporosis and Ultrasound Study is a prospectively designed, population-based European multicenter observational study to evaluate state-of-the-art diagnostic methods for assessing osteoporosis. A total 2837 women underwent dual x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). Prevalent vertebral fractures were determined by a centralized radiology laboratory on the basis of radiographs. The data-mining algorithm includes three steps: defining the criteria for node splitting and selection of the best diagnostic test on the basis of the area under the curve, using a random forest to estimate the probability of DXA being the preferred diagnostic method for each participant, and building a single regression tree to describe subgroups for which either DXA or QUS is the more accurate test or for which the two tests are equivalent. Results For participants with weights ≤54.5 kg, QUS had a higher area under the curve in identifying prevalent vertebral fracture. For participants whose weights were >58.5 kg and whose heights were ≤167.5 cm, DXA was better, and for the remaining participants, DXA and QUS had comparable accuracy and could be used interchangeably. Conclusions The proposed tree-structured subgroup analysis successfully defines subgroups and their best diagnostic tests. The method can be used to develop optimal diagnostic strategies in personalized medicine

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene-targeted replacement mice

Scope Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. Methods and results Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX

Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: −0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD) n = 14) from those without osteoporosis (δ44/42CaBlood: −0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were − 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis