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

OBJECTIVE: To determine whether type 1 diabetes and its complications are associated with bone geometry and microarchitecture. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Erosion Identification in Metacarpophalangeal Joints in Rheumatoid Arthritis using High-Resolution Peripheral Quantitative Computed Tomography.

Bone erosions are a pathological feature of several forms of inflammatory arthritis including rheumatoid arthritis (RA). The increased presence and size of erosions are associated with poor outcomes, joint function, and disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization of bone erosions. However, at this resolution, discontinuities in the cortical shell (cortical breaks) that are associated with normal physiological processes and pathology are also visible. The Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis previously used a consensus process to develop a definition of pathological erosion in HR-pQCT: a cortical break detected in at least two consecutive slices, in at least two perpendicular planes, non-linear in shape, with underlying trabecular bone loss. However, despite the availability of a consensus definition, erosion identification is a demanding task with challenges in inter-rater variability. The purpose of this work is to introduce a training tool to provide users with guidance on identifying pathological cortical breaks on HR-pQCT images for erosion analysis. The protocol presented here uses a custom-built module (Bone Analysis Module (BAM) - Training), implemented as an extension to an open-source image processing software (3D Slicer). Using this module, users can practice identifying erosions and compare their results to erosions annotated by expert rheumatologists.

Interactions Between HR-pQCT Bone Density and D3 Cr Muscle Mass (or HR-pQCT Bone Structure and HR-pQCT Muscle Density) in Predicting Fractures: The Osteoporotic Fractures in Men Study.

We examined if an interaction exists between bone and muscle in predicting fractures in older men. Prospective data from the Osteoporotic Fractures in Men study was used to build Cox proportional hazards models. Predictors included HR-pQCT total volumetric BMD (Tt.BMD), trabecular BMD (Tb.BMD), cortical BMD (Ct.BMD) and cortical area (Ct.Ar) at distal radius/tibia, HR-pQCT muscle volume and density (diaphyseal tibia), D3 -creatine dilution (D3 Cr) muscle mass, and grip strength and leg force, analyzed as continuous variables and as quartiles. Incident fractures were self-reported every 4 months via questionnaires and centrally adjudicated by physician review of radiology reports. Potential confounders (demographics, comorbidities, lifestyle factors, etc.) were considered. A total of 1353 men (mean age 84.2 ± 4.0 years, 92.7% white) were followed for 6.03 ± 2.11 years. In the unadjusted (continuous) model, there were no interactions (p > 0.05) between any muscle variable (D3 Cr muscle mass, muscle volume, muscle density, grip strength or leg force) and Tt.BMD at distal radius/tibia for fractures (all: n = 182-302; nonvertebral: n = 149-254; vertebral: n = 27-45). No consistent interactions were observed when interchanging Tt.BMD for Tb.BMD/Ct.BMD or for Ct.Ar (bone structure) at the distal radius/tibia in the unadjusted (continuous) models. Compared with men in quartiles (Q) 2-4 of D3 Cr muscle mass and Q2-4 of distal tibia Tt.BMD, men in Q1 of both had increased risk for all fractures (hazard ratio (HR) = 2.00; 95% confidence interval [CI] 1.24-3.23, p = 0.005) and nonvertebral fractures (HR = 2.10; 95% CI 1.25-3.52, p < 0.001) in the multivariable-adjusted model. Confidence intervals overlapped (p > 0.05) when visually inspecting other quartile groups in the multivariable-adjusted model. In this prospective cohort study of older men, there was no consistent interactions between bone and muscle variables on fracture risk. Larger sample sizes and longer follow-up may be needed to clarify if there is an interaction between bone and muscle on fracture risk in men. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Laplace-Hamming Binarization Approach for Second-Generation HR-pQCT Rescues Fine Feature Segmentation.

Although second-generation high-resolution peripheral quantitative computed tomography (XCTII) provides the highest-resolution in vivo bone microstructure assessment, the manufacturer's standard image processing protocol omits fine features in both trabecular and cortical compartments. To optimize fine structure segmentation, we implemented a binarization approach based on a Laplace-Hamming (LH) segmentation and documented the reproducibility and accuracy of XCTII structure segmentation using both the standard Gaussian-based binarization and the proposed LH segmentation approach. To evaluate reproducibility, 20 volunteers (9 women, 11 men; aged 23-75 years) were recruited, and three repeat scans of the radii and tibias were acquired using the manufacturer's standard in vivo protocol. To evaluate accuracy, cadaveric structure phantoms (14 radii, 6 tibias) were scanned on XCTII using the same standard in vivo protocol and on µCT at 24.5 µm resolution. XCTII images were analyzed twice-first, with the manufacturer's standard patient evaluation protocol and, second, with the proposed LH segmentation approach. The LH approach rescued fine features evident in the grayscale images but omitted or overrepresented (thickened) by the standard approach. The LH approach significantly reduced error in trabecular volume fraction (BV/TV) and thickness (Tb.Th) compared with the standard approach; however, higher error was introduced for trabecular separation (Tb.Sp). The LH approach improved the correlation between XCTII and µCT for cortical porosity (Ct.Po) and significantly reduced error in cortical pore diameter (Ct.Po.Dm) compared with the standard approach. The LH approach resulted in improved precision compared with the standard approach for BV/TV, Tb.Th, Ct.Po, and Ct.Po.Dm at the radius and for Ct.Po at the tibia. Our results suggest that the proposed LH approach produces substantially improved binary masks, reduces proportional bias, and provides greater accuracy and reproducibility in important outcome metrics, all due to more accurate segmentation of the fine features in both trabecular and cortical compartments. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Analysis of Hand Joint Space Morphology in Women and Men with Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) causes unbalanced iron deposition in many organs including the joints leading to severe cartilage loss and bone damage in the metacarpophalangeal joints (MCPJ). High-resolution peripheral quantitative computed tomography (HR-pQCT) and its joint space width (JSW) quantification algorithm quantifies in vivo 3D joint morphology. We therefore aimed to (i) determine feasibility and performance of the JSW algorithm in HH, (ii) quantify joint space morphology, and (iii) investigate the relationship between morphological and clinical parameters in HH. Here, we performed an exploratory study on 24 HH patients and sex- and age-matched controls using HR-pQCT imaging of MCPJ. Mineralized bone structure was automatically segmented from the grayscale image data and periosteal surface bone masks and joint space masks were generated. Mean, minimal, and maximal joint space width (JSW; JSW.MIN; JSW.MAX), JSW heterogeneity (JSW.SD), JSW asymmetry (JSW.AS), and joint space volume (JSV) were computed. Demographics and, for HH patients, disease-specific parameters were recorded. Segmentation of JS was very good with 79.7% of MCPJs successfully segmented at first attempt and 20.3% requiring semi-manual correction. HH men showed larger JSV at all MCPs (+ 25.4% < JSV < + 41.8%, p < 0.05), larger JSW.MAX at MCP 3-4 (+ 14%, 0.006 < p < 0.062), and wider JSW (+ 13%, p = 0.043) at MCP 4 relative to HH women. Compared to controls, both HH men and HH women showed larger JSW.AS and smaller JSW.MIN at all MCP levels, reaching significance for HH men at MCP 2 and 3 (JSW.AS: + 323% < JSW.AS < + 359%, 0.020 < p < 0.043; JSW.MIN: - 216% < JSW.MIN < - 225%, p < 0.043), and for women at MCP 3 (JSW.AS: + 180%, p = 0.025; JSW.MIN: - 41.8%, p = 0.022). Time since HH diagnosis was correlated positively with MCP 4 JSW.AS and JSW.SD (0.463 < ρ < 0.499, p < 0.040), and the number of phlebotomies since diagnosis was correlated with JSW.SD at all MCPs (0.432 < ρ < 0.535, p < 0.050). HR-pQCT-based JSW quantification in MCPJ of HH patients is feasible, performs well even in narrow JS, and allows to define the microstructural joint burden of HH.

Biochemical Markers of Bone Turnover in Older Adults With Type 1 Diabetes.

CONTEXT: Type 1 diabetes (T1D) is characterized by high fracture risk, yet little is known regarding diabetes-related mechanisms or risk factors. OBJECTIVE: Determine whether glycemic control, advanced glycation end products (AGEs), and microvascular complications are associated with bone turnover markers among older T1D adults. DESIGN: Cross-sectional. SETTING: Epidemiology of Diabetes Interventions and Complications study (6 of 27 clinical centers). PARTICIPANTS: 232 T1D participants followed for >30 years. EXPOSURES: Glycemic control ascertained as concurrent and cumulative hemoglobin A1c (HbA1c); kidney function, by estimated glomerular filtration rates (eGFR); and AGEs, by skin intrinsic fluorescence. MAIN OUTCOME MEASURES: Serum procollagen 1 intact N-terminal propeptide (PINP), bone-specific alkaline phosphatase (bone ALP), serum C-telopeptide (sCTX), tartrate-resistant acid phosphatase 5b (TRACP5b), and sclerostin. RESULTS: Mean age was 59.6 ±â€…6.8 years, and 48% were female. In models with HbA1c, eGFR, and AGEs, adjusted for age and sex, higher concurrent HbA1c was associated with lower PINP [ß -3.4 pg/mL (95% CI -6.1, -0.7), P = 0.015 for each 1% higher HbA1c]. Lower eGFR was associated with higher PINP [6.9 pg/mL (95% CI 3.8, 10.0), P < 0.0001 for each -20 mL/min/1.73 m2 eGFR], bone ALP [1.0 U/L (95% CI 0.2, 1.9), P = 0.011], sCTX [53.6 pg/mL (95% CI 32.6, 74.6), P < 0.0001], and TRACP5b [0.3 U/L (95% CI 0.1, 0.4), P = 0.002]. However, AGEs were not associated with any bone turnover markers in adjusted models. HbA1c, eGFR, and AGEs were not associated with sclerostin levels. CONCLUSIONS: Among older adults with T1D, poor glycemic control is a risk factor for reduced bone formation, while reduced kidney function is a risk factor for increased bone resorption and formation.

CT Muscle Density, D3Cr Muscle Mass, and Body Fat Associations With Physical Performance, Mobility Outcomes, and Mortality Risk in Older Men.

BACKGROUND: Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear. METHOD: In a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years. RESULTS: In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively. CONCLUSIONS: Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

Augmenting Osteoporosis Imaging with Machine Learning.

PURPOSE OF REVIEW: In this paper, we discuss how recent advancements in image processing and machine learning (ML) are shaping a new and exciting era for the osteoporosis imaging field. With this paper, we want to give the reader a basic exposure to the ML concepts that are necessary to build effective solutions for image processing and interpretation, while presenting an overview of the state of the art in the application of machine learning techniques for the assessment of bone structure, osteoporosis diagnosis, fracture detection, and risk prediction. RECENT FINDINGS: ML effort in the osteoporosis imaging field is largely characterized by "low-cost" bone quality estimation and osteoporosis diagnosis, fracture detection, and risk prediction, but also automatized and standardized large-scale data analysis and data-driven imaging biomarker discovery. Our effort is not intended to be a systematic review, but an opportunity to review key studies in the recent osteoporosis imaging research landscape with the ultimate goal of discussing specific design choices, giving the reader pointers to possible solutions of regression, segmentation, and classification tasks as well as discussing common mistakes.

Global and Spatial Compartmental Interrelationships of Bone Density, Microstructure, Geometry and Biomechanics in the Distal Radius in a Colles' Fracture Study Using HR-pQCT.

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.

Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures-A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography.

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.

Differences in bone mineral density and morphometry measurements by fixed versus relative offset methods in high-resolution peripheral quantitative computed tomography.

INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT), which enables in vivo analysis of bone morphometry, is widely used in osteoporosis research. The scan position is usually determined by the fixed offset method; however, there are concerns that the scan position can become relatively proximal if limb length is short. The present study compared bone mineral density and morphometry measured using the fixed and relative offset methods, in which the scan position is determined based on the lengths of the forearm and lower leg, and investigated factors responsible for measurement differences between the two methods. METHODS: A total of 150 healthy Japanese subjects, comprising 75 men and 75 women, with a mean age of 45.1 years, were enrolled in this study. The distal radius and tibia were scanned using the fixed and relative offset methods; the fixed offset method involved scanning the radius and tibia at 9 mm and 22 mm, respectively, proximal to their distal articular surfaces. By contrast, the relative offset method entailed scanning the radius at 4% of the forearm length and the tibia at 7.3% of the lower leg length, proximal to their respective distal articular surfaces. The percent overlap between the scan positions of the two methods was measured using the scout views. Measurement values obtained with the two methods were compared. The correlation between the differences in the values among the two methods and forearm length, lower leg length, and body height was examined. RESULTS: The subjects had a mean height of 164.3 ± 14.3 cm, mean forearm length of 252.9 ± 17.3 mm, and mean lower leg length of 346.7 ± 22.3 mm. The mean percent overlap was 85.0 ± 9.1% (59.2-99.6%) for the radius and 79.8 ± 12.5% (48.3-99.8%) for the tibia. Fixed offset scanning yielded higher total volumetric bone mineral density (Tt.vBMD) and cortical vBMD (Ct.vBMD) and greater cortical thickness (Ct.Th) (all p < 0.001). The differences between the two methods in terms of Tt.vBMD, Ct.vBMD and Ct.Th were significantly greater with shorter forearm length, lower leg length, and body height (radius: 0.51 < |r| < 0.63, tibia: 0.61 < |r| < 0.95). CONCLUSION: Measurements of bone mineral density and morphometry obtained using the fixed offset method differed from those obtained using the relative offset method, which takes body size into account. Shorter body height, forearm length, and lower leg length were found to correlate with greater measurement differences. In populations with smaller stature, use of the fixed offset method results in relatively proximal images; thus, caution should be exercised when comparing groups of different height.

Reliability and Change in Erosion Measurements by High-resolution Peripheral Quantitative Computed Tomography in a Longitudinal Dataset of Rheumatoid Arthritis Patients.

OBJECTIVE: The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions. RESULTS: ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819-0.883, and 0.771-0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P = 0.0001 for erosion numbers, width, and depth in axial plane; P = 0.001 for depth in perpendicular plane). CONCLUSION: This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

High-Resolution Peripheral Quantitative Computed Tomography for Bone Evaluation in Inflammatory Rheumatic Disease.

High resolution peripheral quantitative computed tomography (HR-pQCT) is a 3-dimensional imaging modality with superior sensitivity for bone changes and abnormalities. Recent advances have led to increased use of HR-pQCT in inflammatory arthritis to report quantitative volumetric measures of bone density, microstructure, local anabolic (e.g., osteophytes, enthesiophytes) and catabolic (e.g., erosions) bone changes and joint space width. These features may be useful for monitoring disease progression, response to therapy, and are responsive to differentiating between those with inflammatory arthritis conditions and healthy controls. We reviewed 69 publications utilizing HR-pQCT imaging of the metacarpophalangeal (MCP) and/or wrist joints to investigate arthritis conditions. Erosions are a marker of early inflammatory arthritis progression, and recent work has focused on improvement and application of techniques to sensitively identify erosions, as well as quantifying erosion volume changes longitudinally using manual, semi-automated and automated methods. As a research tool, HR-pQCT may be used to detect treatment effects through changes in erosion volume in as little as 3 months. Studies with 1-year follow-up have demonstrated progression or repair of erosions depending on the treatment strategy applied. HR-pQCT presents several advantages. Combined with advances in image processing and image registration, individual changes can be monitored with high sensitivity and reliability. Thus, a major strength of HR-pQCT is its applicability in instances where subtle changes are anticipated, such as early erosive progression in the presence of subclinical inflammation. HR-pQCT imaging results could ultimately impact decision making to uptake aggressive treatment strategies and prevent progression of joint damage. There are several potential areas where HR-pQCT evaluation of inflammatory arthritis still requires development. As a highly sensitive imaging technique, one of the major challenges has been motion artifacts; motion compensation algorithms should be implemented for HR-pQCT. New research developments will improve the current disadvantages including, wider availability of scanners, the field of view, as well as the versatility for measuring tissues other than only bone. The challenge remains to disseminate these analysis approaches for broader clinical use and in research.

Consensus approach for 3D joint space width of metacarpophalangeal joints of rheumatoid arthritis patients using high-resolution peripheral quantitative computed tomography.

BACKGROUND: Joint space assessment for rheumatoid arthritis (RA) by ordinal conventional radiographic scales is susceptible to floor and ceiling effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides superior resolution, and may detect earlier changes. The goal of this work was to compare existing 3D methods to calculate joint space width (JSW) metrics in human metacarpophalangeal (MCP) joints with HR-pQCT and reach consensus for future studies. Using the consensus method, we established reproducibility with repositioning as well as feasibility for use in second-generation HR-pQCT scanners. METHODS: Three published JSW methods were compared using datasets from individuals with RA from three research centers. A SPECTRA consensus method was developed to take advantage of strengths of the individual methods. Using the SPECTRA method, reproducibility after repositioning was tested and agreement between scanner generations was also established. RESULTS: When comparing existing JSW methods, excellent agreement was shown for JSW minimum and mean (ICC 0.987-0.996) but not maximum and volume (ICC 0.000-0.897). Differences were identified as variations in volume definitions and algorithmic differences that generated high sensitivity to boundary conditions. The SPECTRA consensus method reduced this sensitivity, demonstrating good scan-rescan reliability (ICC >0.911) except for minimum JSW (ICC 0.656). There was strong agreement between results from first- and second-generation HR-pQCT (ICC >0.833). CONCLUSIONS: The SPECTRA consensus method combines unique strengths of three independently-developed algorithms and leverages underlying software updates to provide a mature analysis to measure 3D JSW. This method is robust with respect to repositioning and scanner generations, suggesting its suitability for detecting change.

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture-associated differences in HR-pQCT bone parameters; and (2) to determine if HR-pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR-pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta-analysis. An additional meta-analysis of short-term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture-associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR-pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from -2.6% (95% confidence interval [CI] -3.4 to -1.9) in radial cortical vBMD to -12.6% (95% CI -15.0 to -10.3) in radial trabecular vBMD. Fracture-associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR-pQCT can predict incident fracture. Assessment of study quality, heterogeneity, and publication biases verified the validity of these findings. Finally, we demonstrated that fracture-associated deficits in total and trabecular vBMD and certain tibial cortical parameters can be reliably discerned from HR-pQCT-related precision error and can be used to detect fracture-associated differences in individual patients. Although differences in other HR-pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross-sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR-pQCT in clinical fracture prediction. © 2019 American Society for Bone and Mineral Research.

Objective measures of moderate to vigorous physical activity are associated with higher distal limb bone strength among elderly men.

Our aim was to determine the association between objectively measured physical activity (PA) and bone strength of the distal limbs among older men. We studied 994 men from the MrOS cohort study (mean age 83.9) who had repeat (Year 7 and 14) 5-day activity assessment with at least 90% wear time (SenseWearPro3 Armband) and Year 14 measures using high resolution peripheral quantitative tomography (HR-pQCT) (Scanco). Total energy expenditure (TEE), total steps per day, peak cadence (mean of top 30 steps/min over 24 h) and time spent in a given level of activity: sedentary (reference, <1.5 metabolic equivalents of task [METs]), light (1.5 to <3 METs), or moderate to vigorous physical activity(MVPA: ≥3 METs) were calculated as mean over the two time points. Estimated failure load was determined from HR-pQCT data using finite element analysis. We used standardized variables and adjusted for potential confounders using linear regression. The means ±SDs for daily activity were: 2338 ± 356 kcal/d [TEE]; 5739 ± 2696 steps/day [step count], 60 ± 20 cpm [peak cadence], 67 ± 28 min/d [light activity], and 85 ± 52 min/d [MVPA]. Higher TEE, step count, and peak cadence were each associated with higher failure load of the distal radius (effect sizes respectively: 0.13 [95% CI: 0.05, 0.20], 0.11 [95% CI: 0.04, 0.18], and 0.08 [95% CI: 0.01, 0.15]) and higher failure load of the distal tibia (effect sizes respectively 0.21 [95% CI: 0.13, 0.28], 0.19 [95% CI: 0.13, 0.26], 0.19 [95% CI, 0.13, 0.25]). Time spent in MVPA vs. time sedentary was related to bone strength at both sites after adjustment, whereas time spent in light activity vs. time sedentary was not. TEE was associated with compartmental area and BMD parameters at distal tibia, but only area parameters at the distal radius. In summary, MVPA over a 7-year period of time may have a modest association with bone strength and geometry among older men.

Hip Fracture Discrimination Based on Statistical Multi-parametric Modeling (SMPM).

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.