High-resolution Peripheral Quantitative Computed Tomography Research Articles

The Effectiveness of a Lactobacilli-Based Probiotic Food Supplement on Bone Mineral Density and Bone Metabolism in Australian Early Postmenopausal Women: Protocol for a Double-Blind Randomized Placebo-Controlled Trial

Osteoporosis affects one in three women over the age of 50 and results in fragility fractures. Oestrogen deficiency during and after menopause exacerbates bone loss, accounting for higher prevalence of fragility fractures in women. The gut microbiota (GM) has been proposed as a key regulator of bone health, as it performs vital functions such as immune regulation and biosynthesis of vitamins. Therefore, GM modulation via probiotic supplementation has been proposed as a target for potential therapeutic intervention to reduce bone loss. While promising results have been observed in mouse model studies, translation into human trials is limited. Here, we present the study protocol for a double-blind randomized controlled trial that aims to examine the effectiveness of three lactobacilli strains on volumetric bone mineral density (vBMD), trabecular, and cortical microstructure, as measured using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The trial will randomize 124 healthy early postmenopausal women (up to 8 years from menopause) to receive either probiotic or placebo administered once daily for 12 months. Secondary outcomes will investigate the probiotics’ effects on areal BMD and specific mechanistic biomarkers, including bone metabolism and inflammatory markers. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12621000810819).

Homogenized finite element analysis of distal tibia sections: Achievements and limitations

High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia. Despite the capacity of hFE to predict structural properties of distal segments of the radius and the tibia, the limitations of such homogenization scheme remain unclear. Therefore, the objective of this study is to build a complete mechanical data set of the compressive behavior of distal segments of the tibia and to compare quantitatively the structural properties with the hFE predictions. As a further aim, it is intended to verify whether hFE is also able to capture the post-yield strain localisation or fracture zones in such a bone section, despite the absence of strain softening in the constitutive model.Twenty-five fresh-frozen distal parts of tibias of human donors were used in this study. Sections were cut corresponding to an in-house triple-stack protocol HR-pQCT scan, lapped, and scanned using micro computed tomography (μCT). The sections were tested in compression until failure, unloaded and scanned again in μCT. Volumetric bone mineral density (vBMD) and bone mineral content (BMC) were correlated to compression test results. hFE analysis was performed in order to compare computational predictions (stiffness, yield load and plastic deformation field pattern) with the compressive experiment. Namely, strain localization was assessed based on digital volume correlation (DVC) results and qualitatively compared to hFE predictions by comparing mid-slices patterns.Bone mineral content (BMC) showed a good correlation with stiffness (R2 = 0.92) and yield (R2 = 0.88). Structural parameters also showed good agreement between the experiment and hFE for both stiffness (R2 = 0.96, slope = 1.05 with 95 % CI [0.97, 1.14]) and yield (R2 = 0.95, slope = 1.04 [0.94, 1.13]). The qualitative comparison between hFE and DVC strain localization patterns allowed the classification of the samples into 3 categories: bad (15 sections), semi (8), and good agreement (2).The good correlations between BMC or hFE and experiment for structural parameters were similar to those obtained previously for the distal part of the radius. The failure zones determined by hFE corresponded to registration only in 8 % of the cases. We attribute these discrepancies to local elastic/plastic buckling effects that are not captured by the continuum-based FE approach exempt from strain softening. A way to improve strain localization hFE prediction would be to use longer distal segments with intact cortical shells, as done for the radius. To conclude, the used hFE scheme captures the elastic and yield response of the tibia sections reliably but not the subsequent failure process.

Deep Convolutional Neural Networks Provide Motion Grading for High-Resolution Peripheral Quantitative Computed Tomography of the Scaphoid.

In vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) studies on bone characteristics are limited, partly due to the lack of standardized and objective techniques to describe motion artifacts responsible for lower-quality images. This study investigates the ability of such deep-learning techniques to assess image quality in HR-pQCT datasets of human scaphoids. In total, 1451 stacks of 482 scaphoid images from 53 patients, each with up to six follow-ups within one year, and each with one non-displaced fractured and one contralateral intact scaphoid, were independently graded by three observers using a visual grading scale for motion artifacts. A 3D-CNN was used to assess image quality. The accuracy of the 3D-CNN to assess the image quality compared to the mean results of three skilled operators was between 92% and 96%. The 3D-CNN classifier reached an ROC-AUC score of 0.94. The average assessment time for one scaphoid was 2.5 s. This study demonstrates that a deep-learning approach for rating radiological image quality provides objective assessments of motion grading for the scaphoid with a high accuracy and a short assessment time. In the future, such a 3D-CNN approach can be used as a resource-saving and cost-effective tool to classify the image quality of HR-pQCT datasets in a reliable, reproducible and objective way.

Transferability of bone phenotyping and fracture risk assessment by μFRAC from first-generation high-resolution peripheral quantitative computed tomography to second-generation scan data.

The continued development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has led to a second-generation scanner with higher resolution and longer scan region. However, large multi-center prospective cohorts were collected with first-generation HR-pQCT and have been used to develop bone phenotyping and fracture risk prediction (μFRAC) models. This study establishes whether there is sufficient universality of these first-generation trained models for use with second-generation scan data. HR-pQCT data was collected for a cohort of 60 individuals, who had been scanned on both first- and second-generation scanners on the same day to establish the universality of the HR-pQCT models. These data were each used as input to first-generation trained bone microarchitecture models for bone phenotyping and fracture risk prediction, and their outputs were compared for each study participant. Reproducibility of the models were assessed using same-day repeat scans obtained from first-generation (n = 37) and second-generation (n = 74) scanners. Across scanner generations, the bone phenotyping model performed with an accuracy of 93.1%. Similarly, the five-year fracture risk assessment by μFRAC was well correlated with a Pearson's (r) correlation coefficient of r > 0.83 for the three variations of μFRAC (varying inclusion of clinical risk factors, finite element analysis, and dual X-ray absorptiometry). The first-generation reproducibility cohort performed with an accuracy for categorical assignment of 100% (bone phenotyping), and a correlation coefficient of 0.99 (μFRAC), the second-generation reproducibility cohort performed with an accuracy of 96.4% (bone phenotyping), and a correlation coefficient of 0.99 (μFRAC). We demonstrated that bone microarchitecture models trained using first-generation scan data generalize well to second-generation scans, performing with a high level of accuracy and reproducibility. Less than 4% of individuals' estimated fracture risk led to a change in treatment threshold, and in general these dissimilar outcomes using second-generation data tended to be more conservative.

Fracture risk based on HR-pQCT measures does not vary with age in older adults - the bone microarchitecture international consortium (BoMIC) prospective cohort study.

Fracture risk increases with lower areal BMD (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) DXA which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

PPI use is not associated with bone microarchitecture and strength assessed with HR-pQCT after three-years follow-up in patients visiting the Fracture Liaison Service

BackgroundThe use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS). MethodsThis three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56–69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females). ResultsIn total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use. ConclusionCompared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies.

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

IntroductionFracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. MethodsThe study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. ResultsMVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm3 (2.6 %, CI: −77.4, −9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm−3 (17.8 %, CI: 0.01, 0.21 mm−3, p = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm3 (13.7 %, CI: −0.04, −0.004 mm3, p = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, p = 0.048), respectively. ConclusionsThe presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Accuracy and precision of internal displacement and strain measurements in long human bones using HR-pQCT and digital volume correlation

ABSTRACT Digital volume correlation (DVC) is a technique for measuring 3D, internal displacements and strains in loaded structures. One application of DVC is the study of internal bone mechanics and the validation of subject-specific finite element (FE) models. While micro-computed tomography (µCT) is a common choice for DVC studies of small samples of bone, long human bones such as the tibia may exceed the spatial limitations of conventional µCT. High resolution peripheral quantitative CT (HR-pQCT) scanners, with their large bore and open-ended design, may be a viable option for long-bone DVC. However, HR-pQCT is afflicted by stitching artefacts, caused by the stacking of scan blocks to form the large scan volume, resulting in erroneous steps in DVC displacements and bands of increased strain error. This study proposed a modified HR-pQCT scanning protocol and stitching methodology to mitigate the effects of stitching artefacts on DVC measurements of displacement and strain. With the application of the proposed scanning/stitching methodology, displacements greater than 11.7µm (0.29 voxels) and strains greater than 1633µε could be repeatedly measured by DVC. These results show that HR-pQCT combined with DVC is suitable for measuring internal bone displacements in long human bones with sub-voxel precision and strains greater than 1633µε.

Imaging in osteogenesis imperfecta: Where we are and where we are going

Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging. Conventional Radiography and Dual-energy X-ray Absorptiometry (DXA) are currently the two most used imaging modalities in OI. The cardinal radiographic features of OI include generalized osteopenia/osteoporosis, bone deformities, and fractures. DXA is currently the most available technique to assess Bone Mineral Density (BMD), specifically areal BMD (aBMD). However, DXA has important limitations and cannot fully characterize bone fragility in OI based on aBMD. Novel DXA-derived parameters, such as Trabecular Bone Score (TBS), may provide further insight into skeletal changes induced by OI, but evidence is still limited. Techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as problem-solvers or in specific settings, including the evaluation of cranio-cervical abnormalities. Recent evidence supports the use of High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) as a promising tool to improve the characterization of bone fragility in OI. However, HR-pQCT remains a primarily research technique at present. Quantitative Computed Tomography (QCT) is an alternative to DXA for the determination of BMD at central sites, with distinct advantages but considerably higher radiation exposure. Quantitative Ultrasound (QUS) is a portable, inexpensive, and radiation-free modality that may complement DXA evaluation, providing information on bone quality. However, evidence of usefulness of QUS in OI is poor. Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging non-ionizing imaging method that holds promise for the diagnosis of low BMD and for the prediction of fracture risk, but so far only one published study has investigated its role in OI. To conclude, several different radiologic techniques have proven to be effective in the diagnosis and monitoring of OI, each with their own specificities and peculiarities. Clinicians should be aware of the strategic role of the various modalities in the different phases of the patient care process. In this scenario, the development of international guidelines including recommendations on the role of imaging in the diagnosis and monitoring of OI, accompanied by continuous active research in the field, could significantly improve the standardization of patient care.

A243 BONE MINERAL DENSITY AND DIETARY BONE NUTRIENTS DIFFER IN PATIENTS WITH CROHN'S DISEASE STRICTURES

Abstract Background Crohn’s disease (CD) phenotypes include inflammatory (non-stricture) and stricture behaviours. Strictures are bowel narrowing’s that may lead to obstructions and subsequent dietary restrictions to prevent blockages. Bone mineral density (BMD) in CD is affected by many factors including corticosteroid use, CD itself, but also dietary changes. Clinical gold standard for measuring BMD is by dual x-ray absorptiometry (DXA) scans. High-resolution peripheral quantitative computed tomography (HR-pQCT), a more precise imaging modality assesses volumetric BMD, bone geometry and bone microarchitecture. We aim to compare dietary intake, and bone quality in both stricture and non-stricture CD. Aims To identify nutritional patterns, bone quality differences and deficiencies between two subtypes of CD; including energy intake, dietary components and/or micronutrients Methods Individuals (≥55 years old) with ileal CD strictures (fixed, angulated bowel or thickened bowel with pre-stenotic dilation on diagnostic imaging), or inflammatory CD were prospectively recruited. Patients with short gut, celiac disease, dysphagia history were excluded. All patients completed DXA hip and spine scans and HR-pQCT radius and tibia scans. Dietary assessment questionnaires (Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24), and Diet History Questionnaire III for food frequency over the past year were completed. Results 56 (27 inflammatory (48% female, mean age 64.2, BMI 28.7, 16 years CD duration) and 29 strictures (45% female, mean age 65.9, BMI 27.3, 25 years CD duration, 15 (51.7%) prior bowel resection) were included. 31/56 (55.4%) patients were on biologics and 11 (19.5%) had past corticosteroid exposure. DXA-based BMD for stricture versus non-stricture CD patients was not significantly different at the hip or spine. However, HR-pQCT-based radial total BMD (p=0.03), cortical thickness (p=0.01) and cortical area (p=0.04) were lower in stricture than non-stricture patients.11 (7 stricture, 4 inflammatory) patients with past steroids consumed more dairy (p=0.01), vitamin D (p = 0.04), and calcium (p=0.03) than other CD patients. Stricture patients had significantly less consumption of vitamin K (p=0.001), vegetables (p=0.02), calcium (p=0.03), and dairy (p=0.03). Conclusions Patients with CD strictures have lower BMD and cortical bone quality at the radius than those without strictures. Patients with CD strictures also consume significantly less vitamin K, calcium, and dairy, all vital dietary components to prevent OP, compared to non-stricture patients. Overall, the skeletal fracture risk is likely much greater in CD patients with strictures than without, due to greater inherent bone fragility, and less consumption of key nutrition building blocks of bones. Funding Agencies Koopmans Memorial Research Fund

Bone microarchitectural alterations associated with spinal cord injury: Relation to sex hormones, metabolic factors, and loading

ContextPeople living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. ObjectiveTo determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DesignCross-sectional analyses of bone properties in people with SCI. ParticipantsTwenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). Outcome measuresDistal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (μFEA); sex hormones; metabolic and inflammatory markers. ResultsThe mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score − 3.3), trabecular (−2.93), and cortical vBMD (−1.87), and Failure Load by μFEA (−2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (β = 0.77, p = 0.02), thickness (β = 0.52, p = 0.04) and number (β = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (β = 0.59, p = 0.01), trabecular thickness (β = 0.43, p = 0.04), cortical thickness (β = 0.63, p = 0.01) and cortical porosity (β = 0.74 p = 0.04). ConclusionsRadius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading.ClinicalTrials.gov registration #: (NCT03576001).

High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis

ObjectiveTo assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. MethodsHR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. ResultsForty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66–99%) and 80% (95% CI: 59–93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47–90%) and 95% (95% CI: 76–99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1–3) versus 0 (IQR: 0–1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. ConclusionHR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.

Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges.

Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative CT (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared to axial angle data of 13 young women. In the scans without a deviated axial angle and compared to normative HR-pQCT data, Z-scores at the radius for trabecular BMD, number, and separation were -1.6 ± 1.3, -2.5 ± 1.4, and -2.7 (IQR: 2.7), respectively. They were -1.4 ± 1.5 and -1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed; most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores <-4 or > 4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.

Approaching virtual osteoid volume estimation and in-depth tissue characterization in patients with tumor-induced Osteomalacia.

Tumor-induced osteomalacia (TIO) poses a significant diagnostic challenge, leading to increased disease duration and patient burden also by missing clinical suspicion. Today, diagnosis of osteomalacia relies on invasive iliac crest biopsy, if needed. Therefore, a noninvasive, method would be beneficial for patients with severe osteomalacia, such as TIO, and inform their clinical management to address specific needs, like estimating the regeneration capacity at high osteoid-volumes or the potential of a hungry bone syndrome after tumor-removal. Further, given the lack of comprehensive histological characterization of TIO, there is a need for additional tissue characterization. Our assessment encompassed iliac crest biopsies that were examined using quantitative electron backscattered microscopy (qBEI), Raman spectroscopy, micro-CT and histology to analyze the biopsy tissue. Our clinical assessment encompassed dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography (HR-pQCT) alongside with biochemical analyses and clinical evaluations. Combining imaging and clinical data, we established a model to predict the osteoid volume. We compared 9 TIO patients with 10 osteoporosis (OPO) patients and 10 healthy controls. Histological analyses confirmed a pronounced osteoid volume in TIO patients (OPO: 1.20% ± 1.23% vs. TIO: 23.55% ± 12.23%, p < 0.0005), spectroscopy revealed lower phosphate levels in TIO biopsies. By combining HR-pQCT and laboratory diagnostics, we developed a linear regression model to noninvasively predict the osteoid volume revealing significantly higher modeled OV/BVmodel values of 24.46% ± 14.22% for TIO compared to the control group (5.952% ± 3.44%, p ≤ 0.001). By combining laboratory diagnostics, namely, ALP and Tt.BMDRadius measured by HR-pQCT, we achieved the calculation of the virtual osteoid volume to bone volume ratio (OV/BVmodel) with a significant correlation to histology as well as reliable identification of TIO patients compared to OPO and control. This novel approach is potentially helpful for predicting osteoid volume by noninvasive techniques in diagnostic procedures and improving the clinical management of TIO.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

Early bone loss in patients with obstructive sleep apnea: a cross-sectional study

BackgroundObstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism.MethodsMale participants aged 30–59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia.ResultsNinety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius.ConclusionsIn non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.

Am I big boned? Bone length scaled reference data for HRpQCT measures of the radial and tibial diaphysis in White adults

Cross-sectional size of a long bone shaft influences its mechanical properties. We recently used high-resolution peripheral quantitative computed tomography (HRpQCT) to create reference data for size measures of the radial and tibial diaphyses. However, data did not take into account the impact of bone length. Human bone exhibits relatively isometric allometry whereby cross-sectional area increases proportionally with bone length. The consequence is that taller than average individuals will generally have larger z-scores for bone size outcomes when length is not considered. The goal of the current work was to develop a means of determining whether an individual's cross-sectional bone size is suitable for their bone length. HRpQCT scans performed at 30 % of bone length proximal from the distal end of the radius and tibia were acquired from 1034 White females (age = 18.0 to 85.3 y) and 392 White males (age = 18.4 to 83.6 y). Positive relationships were confirmed between bone length and cross-sectional areas and estimated mechanical properties. Scaling factors were calculated and used to scale HRpQCT outcomes to bone length. Centile curves were generated for both raw and bone length scaled HRpQCT data using the LMS approach. Excel-based calculators are provided to facilitate calculation of z-scores for both raw and bone length scaled HRpQCT outcomes. The raw z-scores indicate the magnitude that an individual's HRpQCT outcomes differ relative to expected sex- and age-specific values, with the scaled z-scores also considering bone length. The latter enables it to be determined whether an individual or population of interest has normal sized bones for their length, which may have implications for injury risk. In addition to providing a means of expressing HRpQCT bone size outcomes relative to bone length, the current study also provides centile curves for outcomes previously without reference data, including tissue mineral density and moments of inertia.

Individual trabecula segmentation validation in first- and second-generation high-resolution peripheral computed tomography compared to micro-computed tomography in the distal radius and tibia.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has been used for in vivo 3D visualization of trabecular microstructure. Second-generation HR-pQCT (HR-pQCT II) has been shown to have good agreement with first generation HR-pQCT (HR-pQCT I). Advanced Individual Trabecula Segmentation (ITS) decomposes the trabecula network into individual plates and rods. ITS based on HR-pQCT I showed a strong correlation to ITS based on micro-computed tomography (μCT) and identified trabecular changes in metabolic bone diseases. ITS based on HR-pQCT II has new potential because of the enhanced resolution but has yet to be validated. The objective of this study was to assess the agreement between ITS based on HR-pQCT I, HR-pQCT II, and μCT to assess the capability of ITS on HR-pQCT images as a tool for studying bone structure. Freshly frozen tibia and radius bones were scanned in the distal region using HR-pQCT I at 82μm, HR-pQCT II at 60.7μm, and μCT at 37μm. Images were registered, binarized, and ITS analysis was performed. Bone volume fraction (pBV/TV, rBV/TV), number density (pTb.N, rTb.N), thickness (pTb.Th, rTb.Th), and plate-to-rod (PR) ratio (pBV/rBV) of trabecular plates and rods were obtained. Paired Student's t-tests with post hoc Bonferroni analysis were used to examine the differences. Linear regression was used to determine the correlation coefficient. The HR-pQCT I parameters were different from the μCT measurements. The HR-pQCT II parameters were different from the μCT measurements except for rTb.N, and the HR-pQCT I parameters were different from the HR-pQCT II measurements except for pTb.Th. The strong correlation between HR-pQCT II and μCT microstructural analysis (R2 = 0.55-0.94) suggests that HR-pQCT II can be used to assess changes in plate and rod microstructure and that values from HR-pQCT I can be corrected.

The Application of Advanced Bone Imaging Technologies in Sports Medicine

Until recently, the evaluation of bone health and fracture risk through imaging has been limited to dual-energy X-ray absorptiometry (DXA) and plain radiographs, with a limited application in the athletic population. Several novel imaging technologies are now available for the clinical assessment of bone health, including bone injury risk and healing progression, with a potential for use in sports medicine. Among these imaging modalities is high-resolution peripheral quantitative computed tomography (HR-pQCT) which is a promising technology that has been developed to examine the bone microarchitecture in both cortical and trabecular bone at peripheral anatomical sites. Technologies that do not expose patients to ionizing radiation are optimal, particularly for athletes who may require frequent imaging. One such alternative is diagnostic ultrasound, which is preferable due to its low cost and lack of radiation exposure. Furthermore, ultrasound, which has not been a common imaging modality for monitoring fracture healing, has been shown to potentially demonstrate earlier signs of union compared to conventional radiographs, including callus mineralization and density at the healing site. Through the use of conventional magnetic resonance imaging (MRI), finite element analysis (FEA) can be used to simulate the structural and mechanical properties of bone. On the other hand, the ultrashort echo time (UTE) MRI can evaluate cortical bone quality by detecting water bound to the organic bone matrix and free water, providing important information about bone porosity. Several novel bone imaging techniques originally developed for osteoporosis assessment have great potential to be utilized to improve the standard of care in bone fracture risk assessment and healing in sports medicine with much greater precision and less adverse radiation exposure.

Diabetes Risk Factors and Bone Microarchitecture as Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Adults With Long-Standing Type 1 Diabetes.

To determine whether type 1 diabetes and its complications are associated with bone geometry and microarchitecture. This cross-sectional study was embedded in a long-term observational study. High-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal and diaphyseal tibia were performed in a subset of 183 participants with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study and 94 control participants without diabetes. HbA1c, skin advanced glycation end products (AGEs), and diabetes-related complications were assessed in EDIC participants with >30 years of follow-up. Compared with control participants (aged 60 ± 8 years, 65% female), EDIC participants (aged 60 ± 7 years, diabetes duration 38 ± 5 years, 51% female) had lower total bone mineral density (BMD) at the distal radius (-7.9% [95% CI -15.2%, -0.6%]; P = 0.030) and distal tibia (-11.3% [95% CI -18.5%, -4.2%]; P = 0.001); larger total area at all sites (distal radius 4.7% [95% CI 0.5%, 8.8%; P = 0.030]; distal tibia 5.9% [95% CI 2.1%, 9.8%; P = 0.003]; diaphyseal tibia 3.4% [95% CI 0.8%, 6.1%; P = 0.011]); and poorer radius trabecular and cortical microarchitecture. Estimated failure load was similar between the two groups. Among EDIC participants, higher HbA1c, AGE levels, and macroalbuminuria were associated with lower total BMD. Macroalbuminuria was associated with larger total area and lower cortical thickness at the distal radius. Higher HbA1c and AGE levels and lower glomerular filtration rate, peripheral neuropathy, and retinopathy were associated with deficits in trabecular microarchitecture. Type 1 diabetes is associated with lower BMD, larger bone area, and poorer trabecular microarchitecture. Among participants with type 1 diabetes, suboptimal glycemic control, AGE accumulation, and microvascular complications are associated with deficits in bone microarchitecture and lower BMD.