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Purpose: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly., Methods: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D)., Results: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563)., Conclusions: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The impact of dietary counseling on body composition in early breast cancer patients (EBC) treated with aromatase inhibitors (AIs) is uncertain. The aim of this study was to assess the effects of a diet counseling program on weight, BMI, total and regional body composition in patients treated with AIs., Methods: This observational study involved 194 EBC patients, of which 97 attended a 6-month personalized counseling program, based on Mediterranean diet principles (cohort A) and 97 did not (cohort B). Dual-energy X-ray absorptiometry (DXA) scan was used to measure the total and regional fat and lean body mass, before (baseline) and after at least 18 months of AI-therapy., Results: Weight and BMI increased significantly, on the average, in cohort B, but not in cohort A. In the cohorts A and B, fat mass increased by 10 % and 7.7 % respectively, while lean mass decreased by 3.3 % and 2.6 % from before to after AI therapy, without statistically significant differences between them using the Mann-Whitney test. The changes in body composition were greater in premenopausal than in postmenopausal women at cancer diagnosis. The proportion of patients with sarcopenia, obesity and sarcopenic obesity increased from before to after AI therapy, similarly in both cohorts., Conclusions: Patients treated with AIs reported an increase in fat mass and a decrease in lean mass, and consequently an increase in sarcopenia and obesity, regardless of the participation in a dietary counseling program. A combined dietary counseling and physical exercise program may be necessary for preventing these unfavourable changes in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bone Strain Index (BSI) is a new dual-energy x-ray absorptiometry (DXA)-based index. We retrospectively evaluated data from 153 postmenopausal women with a history of type 2 diabetes mellitus (T2DM). Lumbar spine and femoral Bone Strain Index (BSI) were sensitive to skeletal impairment in postmenopausal women suffering from T2DM., Purpose: Bone Strain Index (BSI) is a new dual-energy X-ray absorptiometry (DXA)-based measurement. We evaluated the performance of BSI in predicting the presence of fragility fractures in type 2 diabetes mellitus (T2DM) postmenopausal women., Methods: We retrospectively evaluated data from a case-control study of 153 postmenopausal women with a history of at least 5 years of T2DM (age from 40 to 90 years). For each subject, we assessed the personal or familiar history of previous fragility fractures and menopause age, and we collected data about bone mineral density (BMD), BSI, and Trabecular Bone Score (TBS) measurements. Statistical analysis was performed having as outcome the history of fragility fractures., Results: Out of a total of 153 subjects, n = 22 (14.4%) presented at least one major fragility fracture. A negative correlation was found between lumbar BSI and lumbar BMD (r =  - 0.49, p < 0.001) and between total femur BSI and total femur BMD (r =  - 0.49, p < 0.001). A negative correlation was found between femoral neck BSI and femoral neck BMD (r =  - 0.22, p < 0.001). Most DXA-based variables were individually able to discriminate between fractured and non-fractured subjects (p < 0.05), and lumbar BSI was the index with the most relative difference between the two populations, followed by femoral BSI., Conclusion: Lumbar spine and femoral BSI are sensitive to skeletal impairment in postmenopausal women suffering from T2DM. The use of BSI in conjunction with BMD and TBS can improve fracture risk assessment., (© 2024. The Author(s).)

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice., Purpose: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae., Methods: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness., Results: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06)., Conclusion: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Bone Strain Index (BSI), based on dual-energy X-ray absorptiometry (DXA), is a densitometric index of bone strength of the femur and lumbar spine. Higher BSI values indicate a higher strain applied to bone, predisposing to higher fracture risk. This retrospective, multicentric study on Italian women reports the BSI normative age-specific reference curves. A cohort of Caucasian Italian women aged 20 to 90 years was selected from three different clinical centres. Bone mineral density (BMD) and BSI measurements were obtained for the lumbar spine vertebrae (L1-L4) and for the femur (neck, trochanter and intertrochanter) using Hologic densitometers scans. The data were compared with BMD normative values provided by the densitometer manufacturer. Then, the age-specific BSI curve for the femur and lumbar spine was generated. No significant difference was found between the BMD of the subjects in this study and BMD reference data provided by Hologic ( p = 0.68 for femur and p = 0.90 for lumbar spine). Spine BSI values (L1-L4) increase by 84% between 20 and 90 years of age. The mean BSI of the total femur increases about 38% in the same age range. The BSI age-specific reference curve could help clinicians improve osteoporosis patient management, allowing an appropriate patient classification according to the bone resistance to the applied loads and fragility fracture risk assessment.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT., Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t -test or sign test and Pearson or Spearman tests for continuous variables were used when indicated., Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms ( r = 0.36) and legs ( r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM ( r = 0.52, p = 0.006), fat mass at arms ( r = 0.54, p = 0.004), and fat mass at trunk ( r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed ( r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation., Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT., Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript., Clinical Trial Number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10., Competing Interests: MB, AD, CP, SZ, LT, MZ, ML, ND, IC, RB, FV, PB, AG, DF, AA, CS, GM, AB No competing interests declared, LR L Rinaudo is affiliated with Tecnologie Avanzate S.r.l. The author has no financial interests to declare, (© 2024, Bergamini et al.)

Importance: Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date., Objectives: To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM., Design, Setting, and Participants: For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022., Exposure: Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy., Main Outcomes and Measures: VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points., Results: Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression., Conclusions and Relevance: The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

The trabecular and cortical bone assessed by bone strain index seems not to be significantly affected in NHPT., Introduction: The natural history and bone involvement of normocalcemic hyperparathyroidism (NHPT) are not fully clarified yet. The bone strain index (BSI) is a deformation index based on the finite element method and can be applied to DXA scans. In this study, we aim to assess BSI in subjects with NHPT., Method: A case-control study included 170 subjects: 40 subjects with NHPT, 50 subjects with primary hypercalcemic hyperparathyroidism (PHPT), and 80 controls (age- and sex-matched with the NPTH group)., Results: Lumbar spine (LS) bone mineral density (BMD), femoral neck (FN) BMD, total hip (TH) BMD, and TBS were similar between NHPT and both PHPT and controls. FN-BSI was lower in NHPT compared to PHPT (1.52 ± 0.31 vs 1.72 ± 0.42 p = 0.031) while there were no differences between NHPT and controls. TH-BSI was lower in NHPT compared to PHPT (1.36 ± 0.23 vs 1.52 ± 0.34, p = 0.030), while there were no differences between NHPT and controls. LS-BSI was not different between NHPT and both PHPT and controls., Conclusion: The trabecular and cortical bones assessed by BSI seem not to be significantly impaired in NHPT. Further prospective studies are needed to confirm these findings and to give an insight into the natural history of NHPT to improve knowledge and management of this condition., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Context: As patients are now living with prostate cancer for longer, the long-term impact of hormonal treatment on bone health is an increasingly debated subject., Objective: To characterize the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss., Methods: BMD and body composition (lean body mass, fat body mass, and appendicular mass index [ALMI]) were assessed by dual X-ray absorptiometry on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, and 6 and 12 months., Results: Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson r = -0.62, P < .0001) and month 12 (Pearson r = -0.41, P = .032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson r = -0.43, P = .019) and a direct relationship between changes of ALMI and ALP (Pearson r = 0.44, P = .016) during degarelix therapy were observed., Conclusion: Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy, and ALMI changes during therapy are associated with bone turnover derangement favoring bone quality alterations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Bone Strain Index (BSI) is a recently developed dual-energy X-ray absorptiometry (DXA) software, applying a finite element analysis on lumbar spine and femoral DXA scans. BSI is a parameter of bone deformation, providing information on bone resistance to applied loads. BSI values indicate the average bone strain in the explored site, where a higher strain (higher BSI values) suggests a higher fracture risk. This study reports the distributional characteristics of lumbar BSI (L-BSI) in women with normal bone mass, osteopenia or osteoporosis and their relationships with BMD, weight, height and BMI., Material and Methods: Two-hundred-fifty-nine consecutive unfractured women who performed DXA were divided into three groups based on BMD T-score: normal bone mass (n = 43, 16.6%), osteopenia (n = 82, 31.7%) and osteoporosis (n = 134, 51.7%). The distribution of L-BSI was evaluated with conventional statistical methods, histograms and by calculating parametric and nonparametric 95% confidence intervals, together with the 90%, 95% and 99% bilateral tolerance limits with a 95% confidence., Results: Ninety percent bilateral tolerance limits with 95% confidence for L-BSI distribution are 1.0-2.40, 0.95-2.63 and 0.84-3.15 in the group of patients with normal bone mass, 1.34-2.78, 1.24-2.95 and 1.05-3.32 in the osteopenic group and 1.68-3.79, 1.58-4.15 and 1.40-4.96 in the osteoporotic group., Conclusion: In women without vertebral fractures at baseline, L-BSI values from 1.68 (osteoporotic group) and 2.40 (upper of the normal bone mass group) can be tentatively chosen as a lower and upper threshold to stratify postmenopausal women according to their bone resistance to loads., (© 2022. Italian Society of Medical Radiology.)

Bone strain Index (BSI) is an innovative index of bone strength that provides information about skeletal resistance to loads not considered by existing indexes (Bone Mineral Density, BMD. Trabecular Bone Score, TBS. Hip Structural Analysis, HSA. Hip Axis Length, HAL), and, thus, improves the predictability of fragility fractures in osteoporotic patients. This improved predictability of fracture facilitates the possibility of timely intervention with appropriate therapies to reduce the risk of fracture. The development of the index was the result of combining clinical, radiographical and construction-engineering skills. In fact, from a physical point of view, primary and secondary osteoporosis, leading to bone fracture, are determined by an impairment of the physical properties of bone strength: density, internal structure, deformation and fatigue. Dual X-ray absorptiometry (DXA) is the gold standard for assessing bone properties, and it allows measurement of the BMD, which is reduced mainly in primary osteoporosis, the structural texture TBS, which can be particularly degraded in secondary osteoporosis, and the bone geometry (HSA, HAL). The authors recently conceived and developed a new bone deformation index named Bone Strain Index (BSI) that assesses the resistance of bone to loads. If the skeletal structure is equated to engineering construction, these three indexes are all considered to determine the load resistance of the construct. In particular, BSI allows clinicians to detect critical information that BMD and TBS cannot explain, and this information is essential for an accurate definition of a patient's fracture risk. The literature demonstrates that both lumbar and femoral BSI discriminate fractured osteoporotic people, that they predict the first fragility fracture, and further fragility fractures, monitor anabolic treatment efficacy and detect patients affected by secondary osteoporosis. BSI is a new diagnostic tool that offers a unique perspective to clinical medicine to identify patients affected by primary and, specially, secondary osteoporosis. This literature review illustrates BSI's state of the art and its ratio in clinical medicine.

Recently, the bone strain index (BSI), a new index of bone strength based on a finite element model (FEA) from dual X-ray absorptiometry (DXA), has been developed. BSI represents the average equivalent strain inside the bone, assuming that a higher strain level (high BSI) indicates a condition of higher risk. Our study aimed to analyze the relationship between BSI and age, BMI and areal BMD in pre- and postmenopausal women and to prospectively investigate fracture prediction (Fx) by BSI in postmenopausal women. Methods. At the 14th annual follow-up of the OFELY study, BSI was measured at spine (Spine BSI) and femoral scans (Neck and Total Hip BSI), in addition to areal BMD with DXA (Hologic QDR 4500) in 846 women, mean (SD) age 60 yr (15). The FRAX® (fracture risk assessment tool) for major osteoporotic fractures (MOF) was calculated with FN areal BMD (aBMD) at baseline; incident fragility fractures were annually registered until January 2016. Results. In premenopausal women (n = 261), Neck and Total Hip BSI were slightly negatively correlated with age (Spearman r = -0.13 and -0.15 respectively, p = 0.03), whereas all BSIs were positively correlated with BMI (r = +0.20 to 0.37, p < 0.01) and negatively with BMD (r = -0.69 to -0.37, p < 0.0001). In postmenopausal women (n = 585), Neck and Total Hip BSI were positively correlated with age (Spearman r = +0.26 and +0.31 respectively, p < 0.0001), whereas Spine BSI was positively correlated with BMI (r = +0.22, p < 0.0001) and all BSIs were negatively correlated with BMD (r = -0.81 to -0.60, p < 0.0001). During a median [IQ] 9.3 [1.0] years of follow-up, 133 postmenopausal women reported an incident fragility Fx, including 80 women with a major osteoporotic Fx (MOF) and 26 women with clinical vertebral Fx (VFx). Each SD increase of BSI value was associated with a significant increase of the risk of all fragility Fx with an age-adjusted HR of 1.23 for Neck BSI (p = 0.02); 1.27 for Total Hip BSI (p = 0.004) and 1.35 for Spine BSI (p < 0.0001). After adjustment for FRAX®, the association remained statistically significant for Total Hip BSI (HR 1.24, p = 0.02 for all fragility Fx; 1.31, p = 0.01 for MOF) and Spine BSI (HR 1.33, p < 0.0001 for all fragility Fx; 1.33, p = 0.005 for MOF; 1.67, p = 0.002 for clinical VFx). In conclusion, spine and femur BSI, an FEA DXA derived index, predict incident fragility fracture in postmenopausal women, regardless of FRAX®., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We applied an artificial intelligence-based model to predict fragility fractures in postmenopausal women, using different dual-energy x-ray absorptiometry (DXA) parameters., Methods: One hundred seventy-four postmenopausal women without vertebral fractures (VFs) at baseline (mean age 66.3 ± 9.8) were retrospectively evaluated. Data has been collected from September 2010 to August 2018. All subjects performed a spine x-ray to assess VFs, together with lumbar and femoral DXA for bone mineral density (BMD) and the bone strain index (BSI) evaluation. Follow-up exams were performed after 3.34 ± 1.91 years. Considering the occurrence of new VFs at follow-up, two groups were created: fractured versus not-fractured. We applied an artificial neural network (ANN) analysis with a predictive tool (TWIST system) to select relevant input data from a list of 13 variables including BMD and BSI. A semantic connectivity map was built to analyse the connections among variables within the groups. For group comparisons, an independent-samples t-test was used; variables were expressed as mean ± standard deviation., Results: For each patient, we evaluated a total of n = 6 exams. At follow-up, n = 69 (39.6%) women developed a VF. ANNs reached a predictive accuracy of 79.56% within the training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map showed that a low BSI at the total femur is connected to the absence of VFs., Conclusion: We found a high performance of ANN analysis in predicting the occurrence of VFs. Femoral BSI appears as a useful DXA index to identify patients at lower risk for lumbar VFs., (© 2021. The Author(s).)

The comprehension of trabecular bone damage processes could be a crucial hint for understanding how bone damage starts and propagates. Currently, different approaches to bone damage identification could be followed. Clinical approaches start from dual X-ray absorptiometry (DXA) technique that can evaluate bone mineral density (BMD), an indirect indicator of fracture risk. DXA is, in fact, a two-dimensional technology, and BMD alone is not able to predict the effective risk of fractures. First attempts in overcoming this issue have been performed with finite element (FE) methods, combined with the use of three-dimensional high-resolution micro-computed tomographic images. The purpose of this work is to evaluate damage initiation and propagation in trabecular vertebral porcine samples using 2D linear-elastic FE models from DXA images and 3D linear FE models from micro-CT images. Results show that computed values of strains with 2D and 3D approaches (e.g., the minimum principal strain) are of the same order of magnitude. 2D DXA-based models still remain a powerful tool for a preliminary screening of trabecular regions that are prone to fracture, while from 3D micro-CT-based models, it is possible to reach details that permit the localization of the most strained trabecula., (© 2021. The Author(s).)

Background: Luteinizing hormone-releasing hormone (LHRH)-agonists in prostate cancer (PCa) patients induce sarcopenic obesity. The effect of LHRH-antagonist on body composition has never been explored. We evaluated changes in fat (FBM) and lean body mass (LBM) in PCa patients undergoing Degarelix., Methods: This is a single-center prospective study, enrolling 29 non-metastatic PCa patients eligible to LHRH-antagonist from 2017 to 2019. All patients received monthly subcutaneous injection of Degarelix for 12 months. Changes in FBM and LBM between baseline and 12-month Degarelix, as measured by dual-energy x-ray absorptiometry, were the co-primary endpoints. Secondary endpoints were changes in serum lipids, glucose profile and follicle-stimulating hormone (FSH). Appendicular lean mass index (ALMI) and ALMI/FBM ratio were assessed as post-hoc analyses. Linear mixed models with random intercept tested for estimated least squared means differences (EMD)., Results: FBM significantly increased after 12 months (EMD +2920.7, +13.8%, p < 0.001), whereas LBM remained stable (EMD -187.1, -0.3%, p = 0.8). No differences occurred in lipid profile. Glycated hemoglobin significantly increased and serum FSH significantly decreased. A significant inverse relationship was found between serum FSH and ALMI/FBM ratio after 12 month (r = -0.44, p = 0.02)., Conclusions: The BLADE study prospectively evaluated changes in body composition after LHRH-antagonist. LHRH-antagonist therapy is associated to an increased risk of obesity and diabetes, but lean body mass and serum lipids are not affected. This may represent an additional evidence supporting the reduced cardiovascular risk associated with LHRH-antagonist. The role of FSH in influencing sarcopenic obesity in PCa after androgen deprivation deserves to be further explored., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: Primary hyperparathyroidism (PHPT) is associated with impaired bone quality and increased fracture risk. Reliable tools for the evaluation of bone quality parameters are not yet clinically available. Bone Strain Index (BSI) is a new metric for bone strength based on Finite Element Analysis from lumbar spine and femoral neck dual-energy x-ray absorptiometry (DXA) images., Objective: To assess the lumbar spine (LS), femoral neck (FN), and total hip (TH) BSI in PHPT patients compared with controls and to investigate the association of BSI with vertebral fractures (VFs) in PHPT., Methods: This case-control study enrolled 50 PHPT patients and 100 age- and sex-matched control subjects from an outpatient clinic. The main outcome measures were LS-BSI, FN-BSI, and TH-BSI., Results: FN bone mineral density (BMD) and one-third distal radius BMD were lower in the PHPT group than in controls (FN 0.633 ± 0.112 vs 0.666 ± 0.081, P = 0.042; radius 0.566 ± 0.07 vs 0.625 ± 0.06, P < 0.001). PHPT group has significant lower TBS score compared with controls (1.24 ± 0.09 vs 1.30 ± 0.10, P < 0.001). BSI was significantly higher at LS (2.28 ± 0.59 vs 2.02 ± 0.43, P = 0.009), FN (1.72 ± 0.41 vs 1.49 ± 0.35, P = 0.001), and TH (1.51 ± 0.33 vs 1.36 ± 0.25, P = 0.002) in PHPT. LS-BSI showed moderate accuracy for discriminating VFs (AUC 0.667; 95% CI, 0.513-0.820). LS-BSI ≥ 2.2 and was a statistically significant independent predictor of VFs, with an adjusted odds ratio ranging from 5.7 to 15.1., Conclusion: BSI, a DXA-derived bone quality index, is impaired in PHPT and may help to identify PHPT subjects at high risk of fractures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bone Strain Index (BSI) is a new finite element analysis tool applied to hip dual energy X-ray absorptiometry scans. The aim of this study was to assess the short-term precision error of BSI on the proximal femur, both on a phantom and patients. The International Society for Clinical Densitometry guidelines were followed for short-term precision error assessment. Dual energy X-ray absorptiometry measurements were performed on an anthropomorphic femur phantom that was scanned twice for 30 times, for a total of 60 scans. For the in vivo part, 30 subjects were scanned twice. BSI precision error was compared to that of bone mineral density (BMD). Both for the phantom and the in vivo study BSI reproducibility was lower compared to that of BMD, as the precision error of BSI resulted 3 times higher compared to that BMD. For phantom measurements, the highest precision value was that of total femur (TF) BMD (coefficient of variation [CoV] = 0.63%, reproducibility = 98.24%), while the lowest precision was the femoral neck (FN) BSI (CoV = 3.08%, reproducibility = 91.48%). Similarly, for the in vivo study, the highest precision was found at TF BMD (CoV = 1.36%, reproducibility = 96.22%), while the lowest value of precision was found for FN BSI (CoV = 4.17%, reproducibility = 88.46%). Reproducibility at TF was always better compared to that of the FN. BSI precision error was about 3 times higher compared to BMD, confirming previous results of lumbar spine BSI. The main source of variability of this new software is related to patient positioning., (Copyright © 2020 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Osteoporosis is an asymptomatic disease of high prevalence and incidence, leading to bone fractures burdened by high mortality and disability, mainly when several subsequent fractures occur. A fragility fracture predictive model, Artificial Intelligence-based, to identify dual X-ray absorptiometry (DXA) variables able to characterise those patients who are prone to further fractures called Bone Strain Index, was evaluated in this study., Methods: In a prospective, longitudinal, multicentric study 172 female outpatients with at least one vertebral fracture at the first observation were enrolled. They performed a spine X-ray to calculate spine deformity index (SDI) and a lumbar and femoral DXA scan to assess bone mineral density (BMD) and bone strain index (BSI) at baseline and after a follow-up period of 3 years in average. At the end of the follow-up, 93 women developed a further vertebral fracture. The further vertebral fracture was considered as one unit increase of SDI. We assessed the predictive capacity of supervised Artificial Neural Networks (ANNs) to distinguish women who developed a further fracture from those without it, and to detect those variables providing the maximal amount of relevant information to discriminate the two groups. ANNs choose appropriate input data automatically (TWIST-system, Training With Input Selection and Testing). Moreover, we built a semantic connectivity map usingthe Auto Contractive Map to provide further insights about the convoluted connections between the osteoporotic variables under consideration and the two scenarios (further fracture vs no further fracture)., Results: TWIST system selected 5 out of 13 available variables: age, menopause age, BMI, FTot BMC, FTot BSI. With training testing procedure, ANNs reached predictive accuracy of 79.36%, with a sensitivity of 75% and a specificity of 83.72%. The semantic connectivity map highlighted the role of BSI in predicting the risk of a further fracture., Conclusions: Artificial Intelligence is a useful method to analyse a complex system like that regarding osteoporosis, able to identify patients prone to a further fragility fracture. BSI appears to be a useful DXA index in identifying those patients who are at risk of further vertebral fractures., Competing Interests: All the authors declare that they have no conflict of interest. The engineer LR, former working in Academic University Politecnico of Turin and now employed at the commercial company "TECHNOLOGIC S.r.l", has extracted and tabulated the densitometric data and has applied the mathematical algorithms based on the finite element analysis to calculate the Bone Strain Index. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

For a proper assessment of osteoporotic fragility fracture prediction, all aspects regarding bone mineral density, bone texture, geometry and information about strength are necessary, particularly in endocrinological and rheumatological diseases, where bone quality impairment is relevant. Data regarding bone quantity (density) and, partially, bone quality (structure and geometry) are obtained by the gold standard method of dual X-ray absorptiometry (DXA). Data about bone strength are not yet readily available. To evaluate bone resistance to strain, a new DXA-derived index based on the Finite Element Analysis (FEA) of a greyscale of density distribution measured on spine and femoral scan, namely Bone Strain Index (BSI), has recently been developed. Bone Strain Index includes local information on density distribution, bone geometry and loadings and it differs from bone mineral density (BMD) and other variables of bone quality like trabecular bone score (TBS), which are all based on the quantification of bone mass and distribution averaged over the scanned region. This state of the art review illustrates the methodology of BSI calculation, the findings of its in reproducibility and the preliminary data about its capability to predict fragility fracture and to monitor the follow up of the pharmacological treatment for osteoporosis., Competing Interests: The engineer LR, former working in Politecnico of Turin and now employed at the commercial company TECHNOLOGIC S.r.l, has extracted and tabulated the densitometric data and has applied the mathematical algorithms based on the finite element analysis to calculate the Bone Strain Index. TECHNOLOGIC S.r.l. Provided support in the form of salary for LR, but did not have any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ulivieri and Rinaudo.)

Reduced bone mass with or without fragility fractures is a common feature of mastocytosis, particularly in adult males. However, bone mineral density does not account for all the fragility fractures, being a part of them attributable to impairment in bone quality. Aim of this study is to assess the usefulness of DXA-derived geometry and structural indexes in the assessment of bone status in mastocytosis. Ninety-six consecutive patients (46 women and 50 men) affected by cutaneous (CM) or systemic (SM) mastocytosis were studied. Mean age (± SD) was 53.3 ± 14.23. Spine lateral X-rays for Genant's scale, DXA for lumbar (L) and femoral (F) bone mineral density (BMD), bone strain index (BSI), lumbar trabecular bone score (TBS), and hip structural analysis (HSA) were performed. Among the laboratory variables, data of serum tryptase were reported. Tryptase was higher in SM (p = 0.035), inversely correlated with LBMD (r =  - 0.232; p = 0.022) and TBS (r =  - 0.280; p = 0.005), and directly with L-BSI (r = 0.276; p = 0.006). L-BSI remained statistically significant (p = 0.006; adjusted R 2  = 0.101) together with mastocytosis (SM or CM: p = 0.034) in the multivariate regression model with tryptase as dependent variable, being LBMD and TBS not statistically significant (p = 0.887, and p = 0.245, respectively). Tryptase increased about 22 units for each unit increase of L-BSI and about 18 units for SM against CM. L-BSI was lower (p = 0.012), while FN-BSI and FT-BSI were higher in women (p < 0.001) than in men. HSA indexes were significantly higher in men, particularly with SM. SM is a risk factor for reduced bone mass, texture and strength. Since mean L-BSI and Z-modulus of all the femoral sites are statistically higher in men than in female, it could be argued that men have a better femoral bone resistance to bending forces than women, but a worse lumbar bone resistance to compressive loads. DXA indexes of bone quality are useful in mastocytosis' bone assessment and its clinical management.

Dual-energy x-ray absorptiometry (DXA) can provide quantitative (bone mineral density, BMD) and qualitative (trabecular bone score, TBS) indexes of bone status, able to predict fragility fractures in most osteoporotic patients. A new qualitative index of bone strength, based on finite element analysis and named bone strain index (BSI), has been recently developed from lumbar DXA scan. We present the preliminary results about the BSI ability to predict a refracture in patients with fragility fractures. A total of 143 consecutive fractured patients with primary osteoporosis (121 females) performed a spine x-ray examination for the calculation of spine deformity index (SDI) and a DXA densitometry for BMD, TBS, and BSI at basal time and in the follow-up. A refracture was considered as a one-unit increase in SDI. For each unit increase of the investigated indexes, the hazard ratio of refracture, 95% confidence interval, p value, and proportionality test p value were for BSI 1.201, 0.982-1.468, 0.074, and 0.218; for lumbar BMD 0.231, 0.028-1.877, 0.170, and 0.305; and for TBS 0.034, 0.001-2.579, 0.126, and 0.518, respectively. BSI was the index predictive of refracture nearest to statistical significance. If confirmed, it may be used for a better risk assessment of osteoporotic patients.

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems., Competing Interests: Author LR was formerly working in Politecnico of Turin and is now employed by the commercial company: "TECHNOLOGIC S.r.l”, who provided support in the form of salary for author LR. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Bone strain index (BSI) is a dual-energy X-ray absorptiometry (DXA)-derived index of bone strength obtained from lumbar densitometric scan. We estimated the reproducibility of BSI in healthy women with different body mass index., Methods: We enrolled postmenopausal women (mean age ± SD: 66 ± 10 years) divided into three groups (A, B and C) according to body mass index (BMI: < 25; 25-29.9; ≥ 30 kg/m 2 ) and two groups (D and E) according to waist circumference (WC: ≤ 88; > 88 cm), each of 30 subjects. They underwent two DXA examinations with in-between repositioning, according to the International Society for Clinical Densitometry guidelines for precision estimation. Bone mineral density (BMD) and BSI were expressed as g/cm 2 and absolute value, respectively. The coefficient of variation (CoV) was calculated as the ratio between root-mean-square standard deviation and mean; least significant change percentage (LSC%) as 2.77 × CoV; reproducibility as the complement to 100% LSC., Results: BSI increased proportionally to BMI and WC and significantly in group C compared to B and A (p = 0.032 and 0.006, respectively). BSI was significantly higher in E compared to D (p = 0.017), whereas no differences were observed in BMD. Although BSI reproducibility was slightly lower in group C (89%), the differences were not significant between all groups. BMD reproducibility did not significantly differ between all groups., Conclusions: BSI reproducibility was significantly lower than that of BMD and decreased proportionally to BMI and WC increase. This reduction of BSI reproducibility was more pronounced in patients with BMI ≥ 30 and WC > 88, as expected, being BSI a parameter sensible to weight.

Dual Energy X-Ray Absorptiometry (DXA) is currently the most widely adopted non-invasive clinical technique to assess bone mineral density and bone mineral content in human research and represents the primary tool for the diagnosis of osteoporosis. DXA measures areal bone mineral density, BMD, which does not account for the three-dimensional structure of the vertebrae and for the distribution of bone mass. The result is that longitudinal DXA can only predict about 70% of vertebral fractures. This study proposes a complementary tool, based on Finite Element (FE) models, to improve the DXA accuracy. Bone is simulated as elastic and inhomogeneous material, with stiffness distribution derived from DXA greyscale images of density. The numerical procedure simulates a compressive load on each vertebra to evaluate the local minimum principal strain values. From these values, both the local average and the maximum strains are computed over the cross sections and along the height of the analysed bone region, to provide a parameter, named Strain Index of Bone (SIB), which could be considered as a bone fragility index. The procedure is initially validated on 33 cylindrical trabecular bone samples obtained from porcine lumbar vertebrae, experimentally tested under static compressive loading. Comparing the experimental mechanical parameters with the SIB, we could find a higher correlation of the ultimate stress, σULT, with the SIB values (R2adj = 0.63) than that observed with the conventional DXA-based clinical parameters, i.e. Bone Mineral Density, BMD (R2adj = 0.34) and Trabecular Bone Score, TBS (R2adj = -0.03). The paper finally presents a few case studies of numerical simulations carried out on human lumbar vertebrae. If our results are confirmed in prospective studies, SIB could be used-together with BMD and TBS-to improve the fracture risk assessment and support the clinical decision to assume specific drugs for metabolic bone diseases., Competing Interests: The authors have declared that no competing interests exist.

Osteoporotic fracture incidence represents a major social and economic concern in the modern society, where the progressive graying of the population involves an highly increased fracture occurrence. Although the gold standard to diagnose osteoporosis is represented by the T-score measurement, estimated from the Bone Mineral Density (BMD) using Dual-energy X-ray Absorptiometry (DXA), the identification of the subjects at high risk of fracture still remains an issue. From this perspective, the purpose of this work is to investigate the role that DXA-based two-dimensional patient-specific finite element (FE) models of the proximal femur, in combination with T-score, could play in enhancing the risk of fracture estimation. With this aim, 2D FE models were built from DXA images of the 28 post-menopausal female subjects involved. A sideways fall condition was reproduced and a Risk of Fracture ( RF ^ ) was computed on the basis of principal strains criteria. The identified RF ^ was then compared to that derived from the CT-based models developed in a previous study. The 2D and 3D RF ^ turned out to be significantly correlated (Spearman's ρ = 0.66, p < 0.001), highlighting the same patients as those at higher risk. Moreover, the 2D RF ^ resulted significantly correlated with the T-score (Spearman's ρ = -0.69, p < 0.001), and managed to better differentiate osteopenic patients, drawing the attention to some of them. The Hip Structural Analysis (HSA) variables explaining the majority of the variance of the 2D and 3D fracture risk were the same as well, i.e., neck-shaft angle and narrow neck buckling ratio. In conclusion, DXA-based FE models, developable from currently available clinical data, appear promising in supporting and integrating the present diagnostic procedure.

Bone's resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone "quality" impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, μCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture., Competing Interests: We have the following interests. Luca Rinaudo is employed by TECHNOLOGIC S.r.l. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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.