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People living with HIV (PLWH) have increased risk of osteoporosis and fractures. We assessed the proximal femur of PLWH and age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. Results suggest that the trabecular compartment is compromised at fracture-prone regions in the proximal femur of PLWH.IntroductionPeople living with HIV (PLWH) have increased risk of osteoporosis and fractures. However, studies assessing the main determinants of bone strength in the proximal femur exclude this vulnerable population. We assessed the proximal femur of 40 PLWH and 26 age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging.MethodsWe examined cortical volumetric bone mineral density (Ct.vBMD), trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), bone marrow adiposity (BMA), and trabecular number, separation, and bone volume fraction. Parametric comparisons between the two groups were made for the femoral head, femoral neck, trochanter, and total hip using linear regression adjusting for several covariates, including metrics of body composition. In addition, we investigated the associations of BMA with Tb.vBMD and trabecular microarchitecture with Spearman's rank partial correlations.ResultsPLWH had lower Tb.vBMD and deteriorated trabecular microarchitecture in the femoral neck, trochanter and total hip, and elevated BMA in the femoral head, femoral neck, and total hip. Ct.vBMD and Ct.Th were not significantly different between the two groups. BMA was significantly associated with lower Tb.vBMD and deteriorated trabecular microarchitecture in both groups albeit at different femoral regions.ConclusionsOur findings suggest that the trabecular, and not the cortical, compartment is compromised in the proximal femur of PLWH. The observed impairments in fracture-prone regions in PLWH indicate lower femoral strength and suggest higher fracture risk. The inverse associations of BMA with trabecular bone density and microarchitecture quality agree with findings at other anatomic sites and in other populations, suggesting that excess BMA possibly due to a switch from the osteoblast to the adipocyte lineage may be implicated in the pathogenesis of bone fragility at the femur in PLWH.

© 2011 Joseph et al. Introduction: The goals of this study were (i) to compare the prevalence of focal knee abnormalities, the mean cartilage T2relaxation time, and the spatial distribution of cartilage magnetic resonance (MR) T2relaxation times between subjects with and without risk factors for Osteoarthritis (OA), (ii) to determine the relationship between MR cartilage T2parameters, age and cartilage morphology as determined with whole-organ magnetic resonance imaging scores (WORMS) and (iii) to assess the reproducibility of WORMS scoring and T2relaxation time measurements including the mean and grey level co-occurrence matrix (GLCM) texture parameters. Methods: Subjects with risk factors for OA (n = 92) and healthy controls (n = 53) were randomly selected from the Osteoarthritis Initiative (OAI) incidence and control cohorts, respectively. The specific inclusion criteria for this study were (1) age range 45-55 years, (2) body mass index (BMI) of 19-27 kg/m2, (3) Western Ontario and McMaster University (WOMAC) pain score of zero and (4) Kellgren Lawrence (KL) score of zero at baseline. 3.0 Tesla MR images of the right knee were analyzed using morphological gradings of cartilage, bone marrow and menisci (WORMS) as well as compartment specific cartilage T2mean and heterogeneity. Regression models adjusted for age, gender, and BMI were used to determine the difference in cartilage parameters between groups. Results: While there was no significant difference in the prevalence of knee abnormalities (cartilage lesions, bone marrow lesions, meniscus lesions) between controls and subjects at risk for OA, T2parameters (mean T2, GLCM contrast, and GLCM variance) were significantly elevated in those at risk for OA. Additionally, a positive significant association between cartilage WORMS score and cartilage T2parameters was evident. Conclusions: Overall, this study demonstrated that subjects at risk for OA have both higher and more heterogeneous cartilage T2values than controls, and that T2parameters are associated with morphologic degeneration.

SummaryThe standard diagnostic technique for assessing osteoporosis is dual X-ray absorptiometry (DXA) measuring bone mass parameters. In this study, a combination of DXA and trabecular structure parameters (acquired by computed tomography [CT]) most accurately predicted the biomechanical strength of the proximal femur and allowed for a better prediction than DXA alone.IntroductionAn automated 3D segmentation algorithm was applied to determine specific structure parameters of the trabecular bone in CT images of the proximal femur. This was done to evaluate the ability of these parameters for predicting biomechanical femoral bone strength in comparison with bone mineral content (BMC) and bone mineral density (BMD) acquired by DXA as standard diagnostic technique.MethodsOne hundred eighty-seven proximal femur specimens were harvested from formalin-fixed human cadavers. BMC and BMD were determined by DXA. Structure parameters of the trabecular bone (i.e., morphometry, fuzzy logic, Minkowski functionals, and the scaling index method [SIM]) were computed from CT images. Absolute femoral bone strength was assessed with a biomechanical side-impact test measuring failure load (FL). Adjusted FL parameters for appraisal of relative bone strength were calculated by dividing FL by influencing variables such as body height, weight, or femoral head diameter.ResultsThe best single parameter predicting FL and adjusted FL parameters was apparent trabecular separation (morphometry) or DXA-derived BMC or BMD with correlations up to r = 0.802. In combination with DXA, structure parameters (most notably the SIM and morphometry) added in linear regression models significant information in predicting FL and all adjusted FL parameters (up to R(adj) = 0.872) and allowed for a significant better prediction than DXA alone.ConclusionA combination of bone mass (DXA) and structure parameters of the trabecular bone (linear and nonlinear, global and local) most accurately predicted absolute and relative femoral bone strength.

Segmentation of medical images has become an indispensable process to perform quantitative analysis of images of human organs and their functions. Normalized Cuts (NCut) is a spectral graph theoretic method that readily admits combinations of different features for image segmentation. The computational demand imposed by NCut has been successfully alleviated with the Nystrom approximation method for applications different than medical imaging. In this paper we discuss the application of NCut with the Nystrom approximation method to segment vertebral bodies from sagittal T1-weighted magnetic resonance images of the spine. The magnetic resonance images were preprocessed by the anisotropic diffusion algorithm, and three-dimensional local histograms of brightness was chosen as the segmentation feature. Results of the segmentation as well as limitations and challenges in this area are presented.

Magnetic resonance imaging (MRI) T(2) relaxation time assesses non-invasively cartilage composition and can be used as early biomarker for knee osteoarthritis. Most knee cartilage segmentation techniques were primarily developed for volume measurements in DESS or SPGR sequences. For T(2) quantifications, these segmentations need to be superimposed on T(2) maps. However, given that these procedures are time consuming and require manual alignment, using them for analysis of T(2) maps in large clinical trials like the Osteoarthritis Initiative (OAI) is challenging. A novel direct segmentation technique (DST) for T(2) maps was therefore developed. Using the DST, T(2) measurements were performed and compared with those determined with an established segmentation superimposition technique (SST). MR images of five OAI participants were analysed with both techniques three times by one reader and five different images sets additionally with DST three times by two readers. Segmentations and T(2) measurements of one knee required on average 63±3min with DST (vs 302±13min for volume and T(2) measurements with SST). Bland-Altman plots indicated good agreement between the two segmentation techniques, respectively the two readers. Reproducibility errors of both techniques (DST vs SST) were similar (P>0.05) for whole knee cartilage mean T(2) (1.46% vs 2.18%), laminar (up to 2.53% vs 3.19%) and texture analysis (up to 8.34% vs 9.45%). Inter-reader reproducibility errors of DST were higher for texture analysis (up to 15.59%) than for mean T(2) (1.57%) and laminar analysis (up to 2.17%). Due to these results, the novel DST can be recommended for T(2) measurements in large clinical trials like the OAI. [ABSTRACT FROM AUTHOR]

Summary: Objective: The purpose of this study is to determine whether the mean and heterogeneity of magnetic resonance (MR) knee cartilage T2 relaxation time measurements at baseline are associated with morphologic degeneration of cartilage, meniscus, and bone marrow tissues over 3years in subjects with risk factors for osteoarthritis (OA). Design: Subjects with risk factors for OA (n =289) with an age range of 45–55years were selected from the Osteoarthritis Initiative (OAI) database. 3.0 Tesla MR images were analyzed using morphological gradings of cartilage, bone marrow and menisci whole-organ magnetic resonance imaging scores (WORMS scoring). A T2 mapping sequence was used to assess the mean and heterogeneity of cartilage T2 (gray level co-occurrence matrix texture analysis). Regression models were used to assess the relationship between baseline T2 parameters and changes in morphologic knee WORMS scores over 3years. Results: The prevalence of knee abnormalities in the cartilage (P <0.0005), meniscus (P <0.00001), and bone marrow significantly (P <0.00001) increased from baseline to 3years in all compartments combined. The baseline mean and heterogeneity of cartilage T2 were significantly (P <0.05) associated with morphologic joint degeneration in the cartilage, meniscus and bone marrow over 3years. Conclusions: The prevalence of knee abnormalities significantly increased over 3years; increased cartilage T2 at baseline predicted longitudinal morphologic degeneration in the cartilage, meniscus, and bone marrow over 3years in subjects with risk factors for OA. [ABSTRACT FROM AUTHOR]

Summary: Magnetic resonance imaging (MRI) T2 relaxation time assesses non-invasively cartilage composition and can be used as early biomarker for knee osteoarthritis. Most knee cartilage segmentation techniques were primarily developed for volume measurements in DESS or SPGR sequences. For T2 quantifications, these segmentations need to be superimposed on T2 maps. However, given that these procedures are time consuming and require manual alignment, using them for analysis of T2 maps in large clinical trials like the Osteoarthritis Initiative (OAI) is challenging. A novel direct segmentation technique (DST) for T2 maps was therefore developed. Using the DST, T2 measurements were performed and compared with those determined with an established segmentation superimposition technique (SST). MR images of five OAI participants were analysed with both techniques three times by one reader and five different images sets additionally with DST three times by two readers. Segmentations and T2 measurements of one knee required on average 63±3min with DST (vs 302±13min for volume and T2 measurements with SST). Bland–Altman plots indicated good agreement between the two segmentation techniques, respectively the two readers. Reproducibility errors of both techniques (DST vs SST) were similar (P >0.05) for whole knee cartilage mean T2 (1.46% vs 2.18%), laminar (up to 2.53% vs 3.19%) and texture analysis (up to 8.34% vs 9.45%). Inter-reader reproducibility errors of DST were higher for texture analysis (up to 15.59%) than for mean T2 (1.57%) and laminar analysis (up to 2.17%). Due to these results, the novel DST can be recommended for T2 measurements in large clinical trials like the OAI. [Copyright &y& Elsevier]

Purpose: To quantitate bone marrow edema-like lesions (BMELs) and the radiologic properties of cartilage in knees with acute anterior cruciate ligament (ACL) injuries using T(1ρ) magnetic resonance imaging over a 1-year period.Methods: Nine patients with ACL injuries were studied. Magnetic resonance imaging scans were acquired within 8 weeks of the injury, after which ACL reconstruction surgery was performed. Images were then acquired 0.5, 6, and 12 months after reconstructions. The volume and signal intensity of BMELs were quantified at baseline and follow-up examinations. T(1ρ) values were quantified in cartilage overlying the BMEL (OC) and compared with surrounding cartilage at all time points.Results: BMELs were most commonly found in the lateral tibia and lateral femoral condyle. Nearly 50% of BMELs resolved over a 1-year period. The T(1ρ) values of the OC in the lateral tibia, medial tibia, and medial femoral condyle were elevated compared with respective regions in surrounding cartilage at all time points; the difference was significant only in the lateral tibia (P < .05). The opposite results were found in the lateral femoral condyle. For the medial tibia and medial femoral condyle, none of the time periods was significantly different. The percent increase in T(1ρ) values of OC in the lateral tibia was significantly correlated with BMEL volume (r = 0.74, P < .05). At 1 year, the OC in the lateral tibia, medial tibia, and medial femoral condyle showed increased T(1ρ) values despite improvement of BMEL.Conclusions: In patients after ACL tear and reconstruction, (1) the cartilage overlying BMEL in the lateral tibia experiences persistent T(1ρ) signal changes immediately after acute injuries and at 1-year follow-up despite BMEL improvement, (2) the superficial layers of the overlying cartilage show greater matrix damage than the deep layers, and (3) the volume of the BMEL may predict the severity of the overlying matrix's damage in the lateral tibia. T(1ρ) is capable of quantitatively and noninvasively monitoring this damage and detecting early cartilage changes in the lateral tibia over time.Level Of Evidence: Level IV, therapeutic case series. [ABSTRACT FROM AUTHOR]

Purpose: To examine T(1ρ) (T1rho) and T(2) quantitative magnetic resonance imaging (MRI) in evaluating cartilage regeneration following microfracture (MFx) and mosaicplasty (MOS) cartilage resurfacing procedures.Materials and Methods: Eighteen patients underwent MFx and eight patients underwent MOS to treat symptomatic focal cartilage defects. Quantitative T(1ρ) and T(2) maps were acquired at 3-6 months and 1 year after surgery. The area of resurfacing was identified, and T(1ρ) and T(2) values for the regenerated tissue (RT) and normal cartilage (NC) were acquired. RT/NC ratios were calculated to standardize absolute T(1ρ) and T(2) values. Data were prospective, cross-sectional, and nonrandomized.Results: T(1ρ) and T(2) showed good reanalysis reproducibility for RT and NC. Significant differences between RT and NC were present following MFx at 3-6 months for T(1ρ) and T(2) values as well as following MOS at 3-6 months and 1 year for T(1ρ) values. Following MFx, the T(2) RT/NC ratio was significantly different between 3-6 months and 1 year (P = 0.02), while the T(1ρ) RT/NC ratio approached significance (P = 0.07). Following MOS, the T(1ρ) and T(2) RT/NC ratios were not significantly different between the two timepoints.Conclusion: T(1ρ) and T(2) MRI are complementary and reproducible methods for quantitatively and noninvasively monitoring regeneration of RT following MFx and MOS. [ABSTRACT FROM AUTHOR]

(1) To assess the degree of focal cartilage abnormalities in physically active and sedentary healthy subjects as well as in patients with early osteoarthritis (OA). (2) To determine the diagnostic value of T2 and T1rho measurements in identifying asymptomatic physically active subjects with focal cartilage lesions. Thirteen asymptomatic physically active subjects, 7 asymptomatic sedentary subjects, and 17 patients with mild OA underwent 3.0-T MRI of the knee joint. T1rho and T2 values, cartilage volume and thickness, as well as the WORMS scores were obtained. Nine out of 13 active healthy subjects had focal cartilage abnormalities. T1rho and T2 values in active subjects with and without focal cartilage abnormalities differed significantly (p < 0.05). T1rho and T2 values were significantly higher (p < 0.05) in early OA patients compared to healthy subjects. T1rho measurements were superior to T2 in differentiating OA patients from healthy subjects, yet T1rho was moderately age-dependent. (1) Active subjects showed a high prevalence of focal cartilage abnormalities and (2) active subjects with and without focal cartilage abnormalities had different T1rho and T2 composition of cartilage. Thus, T1rho and T2 could be a parameter suited to identify active healthy subjects at higher risk for developing cartilage pathology. [ABSTRACT FROM AUTHOR]

Summary: Objective: The purpose of this study was (1) to characterize the spatial distribution of cartilage T 2 in postmenopausal osteoarthritis (OA) patients and age-matched healthy subjects using second order texture measures at baseline, and (2) to analyze changes in the texture of cartilage T 2 after 9 months. Methods: 3.0T-MRI of the knee was performed in 8 mild OA patients and 10 age-matched controls at baseline and after 9 months. Cartilage T 2, volume, and average thickness were calculated in all patients. Texture analysis, based on the gray level co-occurrence matrix, was performed on the cartilage T 2 maps. Texture parameters, including entropy and angular second moment, were calculated at 0° (corresponding to the anterior–posterior axis) and at 90° (corresponding to the superior–inferior axis), with pixel offsets ranging from 1 to 3 pixels. Results: Least square means analysis showed that mean T 2 values, their standard deviation (SD), and their entropy were greater (P <0.05) in OA patients than in controls. Over 9 months, the SD and entropy of cartilage T 2 significantly (P <0.05) decreased in OA patients, while no significant changes were evident in cartilage thickness or volume. Conclusion: The mean cartilage T 2 values, their SD, and their entropy were greater in OA patients than in controls, indicating that the T 2 values in osteoarthritic cartilage are not only elevated, but also more heterogeneous than those in healthy cartilage. The longitudinal results demonstrate that changes in texture parameters of cartilage T 2 may precede morphological changes in thickness and volume in the progression of OA. [Copyright &y& Elsevier]

Objective: To quantitate longitudinally the radiographic properties of different layers of repaired tissue following microfracture (MFx) surgery using T(1ρ) and T(2) magnetic resonance imaging (MRI).Design: 10 patients underwent MFx surgery to treat symptomatic focal cartilage defects (FCD). Sagittal three-dimensional (3D) water excitation high-spatial resolution (HR) spoiled gradient recalled (SPGR) for quantitative T(1ρ) and T(2) mapping were acquired for each patient 3-6 months and 1 year after surgery. Cartilage compartments were segmented on HR-SPGR images, and T(1ρ) and T(2) maps were registered to the HR-SPGR images. T(1ρ) and T(2) values for the full thickness of deep and superficial layers of repaired tissue (RT) and normal cartilage (NC) were calculated, and compared within and between respective time points. A p-value <0.05 is considered statistically significant.Results: The majority of FCD were found in the MFC. The average surface area of the lesions did not differ significantly overtime. At 3-6 months, RT had significantly higher full thickness T(1ρ) and T(2) values relative to NC. At 1 year, this significant difference was only observed for T(1ρ) values. At 3-6 months follow-up, the RT's superficial layer had significantly higher T(1ρ) and T(2) values than the deep layer of the RT and the superficial layer of NC. At 12 months, the superficial layer of the RT had significantly higher T(1ρ) values than the RT's deep layer and the NC's superficial layer.Conclusion: T(1ρ) and T(2) MRI are feasible methods for quantitatively and noninvasively monitoring the maturation of repaired tissue following microfracture surgery over time. [ABSTRACT FROM AUTHOR]

Background: Among older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use., Methods: All participants will receive the same group-mediated dietary intervention targeting 8-10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT + +PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT + +BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover., Discussion: BEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL., Clinical Trials Registration: NCT05764733., 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 Elsevier Inc. All rights reserved.)

Metabolic bone diseases (MBDs) are a diverse group of diseases, affecting the mass or structure of bones and leading to reduced bone quality. Parameters representing different aspects of bone health can be obtained from various magnetic resonance imaging (MRI) methods such as proton MR spectroscopy, as well as chemical shift encoding-based water-fat imaging, that have been frequently applied to study bone marrow in particular. Furthermore, T2* mapping and high-resolution trabecular bone imaging have been implemented to study bone microstructure. In addition, quantitative susceptibility mapping and ultrashort echo time imaging are used for trabecular and cortical bone assessment. This review offers an overview of technical aspects, as well as major clinical applications and derived main findings, for MRI-based assessment of bone quality in MBDs. It focuses on osteoporosis as the most common MBD., Competing Interests: None declared., (Thieme. All rights reserved.)

A better understanding of how age-related bone loss affects the fracture-prone regions of the proximal femur could lead to more informed fracture-prevention strategies. Therefore, the aim of this work was to assess the spatio-temporal distribution of bone deterioration in older men and women with aging. A subset of 305 men (74.87 ± 4.76 years; mean ± SD) and 371 age-matched women (74.84 ± 4.71 years) with no history of fracture was randomly selected from the Age, Gene/Environment Susceptibility-Reykjavik study. Quantitative computed tomography (QCT) scans of the left proximal femur obtained at baseline and at 5.2 ± 0.4 years follow-up were processed to assess local changes in volumetric bone mineral density (vBMD), cortical bone thickness (Ct.Th), and internal bone structure using voxel-based morphometry (VBM), surface-based statistical parametric mapping (surf-SPM), and tensor-based morphometry (TBM). Local parametric changes within each sex and sex differences in these changes were statistically assessed using linear mixed effects models allowing for baseline and time-varying covariates, yielding Student's t-test and p-value statistical maps of the proximal femur. The statistical maps indicated regions with significant parametric changes in each sex and with significant different parametric changes between older men and older women with aging. Older women manifested significantly larger losses in vBMD, (Ct.Th), and structure than older men, and they did so in regions where deficiency in these parameters has been associated with incident hip fracture. Using longitudinal QCT scans of the proximal femur and Computational Anatomy, we provided new insights into the higher fracture rates of the proximal femur in older women compared with men of similar age providing new information on the pathophysiology of osteoporosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporosis is a highly prevalent systemic skeletal disease that is characterized by low bone mass and microarchitectural bone deterioration. It predisposes to fragility fractures that can occur at various sites of the skeleton, but vertebral fractures (VFs) have been shown to be particularly common. Prevention strategies and timely intervention depend on reliable diagnosis and prediction of the individual fracture risk, and dual-energy X-ray absorptiometry (DXA) has been the reference standard for decades. Yet, DXA has its inherent limitations, and other techniques have shown potential as viable add-on or even stand-alone options. Specifically, three-dimensional (3 D) imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), are playing an increasing role. For CT, recent advances in medical image analysis now allow automatic vertebral segmentation and value extraction from single vertebral bodies using a deep-learning-based architecture that can be implemented in clinical practice. Regarding MRI, a variety of methods have been developed over recent years, including magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) that enable the extraction of a vertebral body's proton density fat fraction (PDFF) as a promising surrogate biomarker of bone health. Yet, imaging data from CT or MRI may be more efficiently used when combined with advanced analysis techniques such as texture analysis (TA; to provide spatially resolved assessments of vertebral body composition) or finite element analysis (FEA; to provide estimates of bone strength) to further improve fracture prediction. However, distinct and experimentally validated diagnostic criteria for osteoporosis based on CT- and MRI-derived measures have not yet been achieved, limiting broad transfer to clinical practice for these novel approaches. KEY POINTS::   · DXA is the reference standard for diagnosis and fracture prediction in osteoporosis, but it has important limitations.. · CT- and MRI-based methods are increasingly used as (opportunistic) approaches.. · For CT, particularly deep-learning-based automatic vertebral segmentation and value extraction seem promising.. · For MRI, multiple techniques including spectroscopy and chemical shift imaging are available to extract fat fractions.. · Texture and finite element analyses can provide additional measures for vertebral body composition and bone strength.. CITATION FORMAT: · Sollmann N, Kirschke JS, Kronthaler S et al. Imaging of the Osteoporotic Spine - Quantitative Approaches in Diagnostics and for the Prediction of the Individual Fracture Risk. Fortschr Röntgenstr 2022; 194: 1088 - 1099., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose of Review: This review article presents the most recent research on bone fragility in individuals with diabetes from a medical imaging perspective., Recent Findings: The widespread availability of dual-energy X-ray absorptiometry (DXA) and trabecular bone score (TBS) software has led to recent assessments of bone fragility with this texture parameter in several studies of type 2 diabetes mellitus (T2D), but in few of type 1 diabetes mellitus (T1D). Although most studies show a trend of reduced TBS values in T2D independent of areal bone mineral density (aBMD) of the lumbar spine, some studies also show the limitations of TBS in both T2D and T1D. Given the limitations of DXA to assess bone strength and investigate the etiology of bone fragility in diabetes, more investigators are incorporating three-dimensional (3D) medical imaging techniques in their studies. Recent use of 3D medical imaging to assess bone fragility in the setting of diabetes has been mostly limited to a few cross-sectional studies predominantly incorporating high-resolution peripheral quantitative computed tomography (HR-pQCT). Although HR-pQCT studies indicate higher tibial cortical porosity in subjects with T2D, results are inconsistent in T1D due to differences in study designs, sample sizes, and subject characteristics, among other factors. With respect to central CT, recent studies support a previous finding in the literature indicating femoral neck geometrical impairments in subjects with T2D and provide encouraging results for the incorporation of finite element analysis (FEA) to assess bone strength in studies of T2D. In the recent literature, there are no studies assessing bone fragility in T1D with QCT, and only two studies used pQCT reporting tibial and radial impairments in young women and children with T1D, respectively. Magnetic resonance imaging (MRI) has not been recently used in diabetic studies of bone fragility., Summary: As bone fragility in diabetes is not explained by DXA-derived aBMD and given the limitations of cross-sectional studies, it is imperative to use 3D imaging techniques for longitudinal assessments of the density, quality, and microenvironment of bone to improve our understanding of the effects of diabetes on bone and reduce the risk of fracture in this large and vulnerable population of subjects with diabetes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine if lateral corticospinal tract (LCST) integrity demonstrates a significant predictive relationship with future ipsilateral lower extremity motor function (LEMS) and if dorsal column (DC) integrity demonstrates a significant predictive relationship with future light touch (LT) sensory function post spinal cord injury (SCI) at time of discharge from inpatient rehabilitation., Design: Retrospective analyses of imaging and clinical outcomes., Setting: University and academic hospital., Participants: A total of 151 participants (N=151) with SCI., Interventions: Inpatient rehabilitation., Main Outcome Measures: LEMS and LT scores at discharge from inpatient rehabilitation., Results: In 151 participants, right LCST spared tissue demonstrated a significant predictive relationship with right LEMS percentage recovered (β=0.56; 95% confidence interval [CI], 0.37-0.73; R=0.43; P<.001). Left LCST spared tissue demonstrated a significant predictive relationship with left LEMS percentage recovered (β=0.66; 95% CI, 0.50-0.82; R=0.51; P<.001). DC spared tissue demonstrated a significant predictive relationship with LT percentage recovered (β=0.69; 95% CI, 0.52-0.87; R=0.55; P<.001). When subgrouping the participants into motor complete vs incomplete SCI, motor relationships were no longer significant, but the sensory relationship remained significant. Those who had no voluntary motor function but recovered some also had significantly greater LCST spared tissue than those who did not recover motor function., Conclusions: LCST demonstrated significant moderate predictive relationships with lower extremity motor function at the time of discharge from inpatient rehabilitation, in an ipsilesional manner. DC integrity demonstrated a significant moderate predictive relationship with recovered function of LT. With further development, these neuroimaging methods might be used to predict potential deficits after SCI and to provide corresponding targeted interventions., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Physical activity enhances proximal femur bone mass, but it remains unclear whether the benefits translate into an enhanced ability to resist fracture related loading. We recently used baseball pitchers as a within-subject controlled model to demonstrate physical activity induced proximal femur adaptation in regions associated with weight bearing and increased strength under single-leg stance loading. However, there was no measurable benefit to resisting common injurious loading (e.g. a fall onto the greater trochanter). A lack of power and a small physical activity effect size may have contributed to the latter null finding. Softball pitchers represent an alternative within-subject controlled model to explore adaptation of the proximal femur to physical activity, exhibiting greater dominant-to-nondominant (D-to-ND) leg differences than baseball pitchers. The current study used quantitative computed tomography, statistical parametric mapping, and subject-specific finite element (FE) modeling to explore adaptation of the proximal femur to physical activity in female softball pitchers (n = 25). Female cross-country runners (n = 15) were included as symmetrically loaded controls, showing very limited D-to-ND leg differences. Softball pitchers had D-to-ND leg differences in proximal femur, femoral neck, and trochanteric volumetric bone mineral density and content, and femoral neck volume. Voxel-based morphometry analyses and cortical bone mapping showed D-to-ND leg differences within a large region connecting the superior femoral head, inferior femoral neck and medial intertrochanteric region, and within the greater trochanter. FE modeling revealed pitchers had 19.4% (95%CI, 15.0 to 23.9%) and 4.9% (95%CI, 1.7 to 8.2%) D-to-ND leg differences in predicted ultimate strength under single-leg stance loading and a fall onto the greater trochanter, respectively. These data affirm the spatial and strength adaptation of the proximal femur to weight bearing directed loading and demonstrate that the changes can also have benefits, albeit smaller, on resisting loads associated with a sideways fall onto the greater trochanter., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoporosis is a systemic skeletal disease with a high prevalence worldwide, characterized by low bone mass and microarchitectural deterioration, predisposing an individual to fragility fractures. Dual-energy X-ray absorptiometry (DXA) has been the clinical reference standard for diagnosing osteoporosis and for assessing fracture risk for decades. However, other imaging modalities are of increasing importance to investigate the etiology, treatment, and fracture risk. The purpose of this work is to review the available literature on quantitative magnetic resonance imaging (MRI) methods and related findings in osteoporosis at the spine and proximal femur as the clinically most important fracture sites. Trabecular bone microstructure analysis at the proximal femur based on high-resolution MRI allows for a better prediction of osteoporotic fracture risk than DXA-based bone mineral density (BMD) alone. In the 1990s, T 2 * mapping was shown to correlate with the density and orientation of the trabecular bone. Recently, quantitative susceptibility mapping (QSM), which overcomes some of the limitations of T 2 * mapping, has been applied for trabecular bone quantifications at the spine, whereas ultrashort echo time (UTE) imaging provides valuable surrogate markers of cortical bone quantity and quality. Magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) enable the quantitative assessment of the nonmineralized bone compartment through extraction of the bone marrow fat fraction (BMFF). Furthermore, CSE-MRI allows for the differentiation of osteoporotic vs. pathologic fractures, which is of high clinical relevance. Lastly, advanced postprocessing and image analysis tools, particularly considering statistical parametric mapping and region-specific BMFF distributions, have high potential to further improve MRI-based fracture risk assessments at the spine and hip. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 2., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Bone parameters derived from HR-pQCT have been investigated on a parameter-by-parameter basis for different clinical conditions. However, little is known regarding the interrelationships of bone parameters and the spatial distribution of these interrelationships. In this work: 1) we investigate compartmental interrelationships of bone parameters; 2) assess the spatial distribution of interrelationships of bone parameters; and 3) compare interrelationships of bone parameters between postmenopausal women with and without a recent Colles' fracture., Methods: Images from the unaffected radius in fracture cases (n=84), and from the non-dominant radius of controls (n=98) were obtained using HR-pQCT. Trabecular voxel-based maps of local bone volume fraction (L.Tb.BV/TV), homogenized volumetric bone mineral density (H.Tb.BMD), homogenized μFEA-derived strain energy density (H.Tb.SED), and homogenized inter-trabecular distances (H.Tb.1/N) were generated; as well as surface-based maps of apparent cortical bone thickness (Surf.app.Ct.Th), porosity-weighted cortical bone thickness (Surf.Ct.SIT), mean cortical BMD (Surf.Ct.BMD), and mean cortical SED (Surf.Ct.SED). Anatomical correspondences across the parametric maps in the study were established via spatial normalization to a common template. Mean values of the parametric maps before spatial normalization were used to assess compartmental Spearman's rank partial correlations of bone parameters (e.g., between H.Tb.BMD and L.Tb.BV/TV or between Surf.Ct.BMD and Surf.app.Ct.Th). Spearman's rank partial correlations were also assessed for each voxel and vertex of the spatially normalized parametric maps, thus generating maps of Spearman's rank partial correlation coefficients. Correlations were performed independently within each group, and compared between groups using the Fisher's Z transformation., Results: All within-group global trabecular and cortical Spearman's rank partial correlations were significant; and the correlations of H.Tb.BMD-L.Tb.BV/TV, H.Tb.BMD-H.Tb.1/N, L.Tb.BV/TV-H.Tb.1/N, Surf.Ct.BMD-Surf.Ct.SED and Surf.Ct.SIT-Surf.Ct.SED were significantly different between controls and fracture cases. The spatial analyses revealed significant heterogeneous voxel- and surface-based correlation coefficient maps across the distal radius for both groups; and the correlation maps of H.Tb.BMD-L.Tb.BV/TV, H.Tb.BMD-H.Tb.1/N, L.Tb.BV/TV-H.Tb.1/N, H.Tb.1/N-H.Tb.SED and Surf.app.Ct.Th - Surf.Ct.SIT yielded small clusters of significant correlation differences between groups., Discussion: The heterogeneous spatial distribution of interrelationships of bone parameters assessing density, microstructure, geometry and biomechanics, along with their global and local differences between controls and fracture cases, may help us further understand different bone mechanisms of bone fracture., Competing Interests: The authors declare 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 Shiraishi, Burghardt, Osaki, Khosla and Carballido-Gamio.)

Introduction: Diabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: Thirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups., Results: At baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020)., Conclusion: Our data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength-depending on the amount of early cortical pre-damage., Competing Interests: AJB has served as a consultant for Ultragenyx Pharmaceutical Inc. and Mereo BioPharma Group PLC, and received research support from Ultragenyx. TML, GJK, JCG, and AJB received grant money from NIH-NIAMS. UH received travel funds from ASBMR. The remaining authors declare 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 Heilmeier, Joseph, Pasco, Dinh, Torabi, Darakananda, Youm, Carballido-Gamio, Burghardt, Link and Kazakia.)

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Studies using quantitative computed tomography (QCT) and data-driven image analysis techniques have shown that trabecular and cortical volumetric bone mineral density (vBMD) can improve the hip fracture prediction of dual-energy X-ray absorptiometry areal BMD (aBMD). Here, we hypothesize that (1) QCT imaging features of shape, density and structure derived from data-driven image analysis techniques can improve the hip fracture discrimination of classification models based on mean femoral neck aBMD (Neck.aBMD), and (2) that data-driven cortical bone thickness (Ct.Th) features can improve the hip fracture discrimination of vBMD models. We tested our hypotheses using statistical multi-parametric modeling (SMPM) in a QCT study of acute hip fracture of 50 controls and 93 fragility fracture cases. SMPM was used to extract features of shape, vBMD, Ct.Th, cortical vBMD, and vBMD in a layer adjacent to the endosteal surface to develop hip fracture classification models with machine learning logistic LASSO. The performance of these classification models was evaluated in two aspects: (1) their hip fracture classification capability without Neck.aBMD, and (2) their capability to improve the hip fracture classification of the Neck.aBMD model. Assessments were done with 10-fold cross-validation, areas under the receiver operating characteristic curve (AUCs), differences of AUCs, and the integrated discrimination improvement (IDI) index. All LASSO models including SMPM-vBMD features, and the majority of models including SMPM-Ct.Th features performed significantly better than the Neck.aBMD model; and all SMPM features significantly improved the hip fracture discrimination of the Neck.aBMD model (Hypothesis 1). An interesting finding was that SMPM-features of vBMD also captured Ct.Th patterns, potentially explaining the superior classification performance of models based on SMPM-vBMD features (Hypothesis 2). Age, height and weight had a small impact on model performances, and the model of shape, vBMD and Ct.Th consistently yielded better performances than the Neck.aBMD models. Results of this study clearly support the relevance of bone density and quality on the assessment of hip fracture, and demonstrate their potential on patient and healthcare cost benefits.

Background: Cortical bone porosity is a major determinant of bone strength. Despite the biomechanical importance of cortical bone porosity, the biological drivers of cortical porosity are unknown. The content of cortical pore space can indicate pore expansion mechanisms; both of the primary components of pore space, vessels and adipocytes, have been implicated in pore expansion. Dynamic contrast-enhanced MRI (DCE-MRI) is widely used in vessel detection in cardiovascular studies, but has not been applied to visualize vessels within cortical bone. In this study, we have developed a multimodal DCE-MRI and high resolution peripheral QCT (HR-pQCT) acquisition and image processing pipeline to detect vessel-filled cortical bone pores., Methods: For this in vivo human study, 19 volunteers (10 males and 9 females; mean age =63±5) were recruited. Both distal and ultra-distal regions of the non-dominant tibia were imaged by HR-pQCT (82 µm nominal resolution) for bone structure segmentation and by 3T DCE-MRI (Gadavist; 9 min scan time; temporal resolution =30 sec; voxel size 230×230×500 µm 3 ) for vessel visualization. The DCE-MRI was registered to the HR-pQCT volume and the voxels within the MRI cortical bone region were extracted. Features of the DCE data were calculated and voxels were categorized by a 2-stage hierarchical kmeans clustering algorithm to determine which voxels represent vessels. Vessel volume fraction (volume ratio of vessels to cortical bone), vessel density (average vessel count per cortical bone volume), and average vessel volume (mean volume of vessels) were calculated to quantify the status of vessel-filled pores in cortical bone. To examine spatial resolution and perform validation, a virtual phantom with 5 channel sizes and an applied pseudo enhancement curve was processed through the proposed image processing pipeline. Overlap volume ratio and Dice coefficient was calculated to measure the similarity between the detected vessel map and ground truth., Results: In the human study, mean vessel volume fraction was 2.2%±1.0%, mean vessel density was 0.68±0.27 vessel/mm 3 , and mean average vessel volume was 0.032±0.012 mm 3 /vessel. Signal intensity for detected vessel voxels increased during the scan, while signal for non-vessel voxels within pores did not enhance. In the validation phantom, channels with diameter 250 µm or greater were detected successfully, with volume ratio equal to 1 and Dice coefficient above 0.6. Both statistics decreased dramatically for channel sizes less than 250 µm., Conclusions: We have a developed a multi-modal image acquisition and processing pipeline that successfully detects vessels within cortical bone pores. The performance of this technique degrades for vessel diameters below the in-plane spatial resolution of the DCE-MRI acquisition. This approach can be applied to investigate the biological systems associated with cortical pore expansion., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.