Dataset Information

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography.

ABSTRACT: Bone marrow adipose tissue (BMAT) has been implicated in a number of conditions associated with bone deterioration and osteoporosis. Several studies have found an inverse relationship between BMAT and bone mineral density (BMD), and higher levels of BMAT in those with prevalent fracture. Magnetic resonance imaging (MRI) is the gold standard for measuring BMAT, but its use is limited by high costs and low availability. We hypothesized that BMAT could also be accurately quantified using high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods

In the present study, a novel method to quantify the tibia bone marrow fat fraction, defined by MRI, using HR-pQCT was developed. In total, 38 postmenopausal women (mean [standard deviation] age 75.9 [3.1] years) were included and measured at the same site at the distal (n = 38) and ultradistal (n = 18) tibia using both MRI and HR-pQCT. To adjust for partial volume effects, the HR-pQCT images underwent 0 to 10 layers of voxel peeling to remove voxels adjacent to the bone. Linear regression equations were then tested for different degrees of voxel peeling, using the MRI-derived fat fractions as the dependent variable and the HR-pQCT-derived radiodensity as the independent variables.

Results

The most optimal HR-pQCT derived model, which applied a minimum of 4 layers of peeled voxel and with more than 1% remaining marrow volume, was able to explain 76% of the variation in the ultradistal tibia bone marrow fat fraction, measured with MRI (p < 0.001).

Conclusion

The novel HR-pQCT method, developed to estimate BMAT, was able to explain a substantial part of the variation in the bone marrow fat fraction and can be used in future studies investigating the role of BMAT in osteoporosis and fracture prediction.

SUBMITTER: Flehr A

PROVIDER: S-EPMC9187531 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography.

Flehr Alison A Källgård Julius J Alvén Jennifer J Lagerstrand Kerstin K Papalini Evin E Wheeler Michael M Vandenput Liesbeth L Kahl Fredrik F Axelsson Kristian F KF Sundh Daniel D Mysore Raghunath Shirish RS Lorentzon Mattias M

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20220203 7

Bone marrow adipose tissue (BMAT) has been implicated in a number of conditions associated with bone deterioration and osteoporosis. Several studies have found an inverse relationship between BMAT and bone mineral density (BMD), and higher levels of BMAT in those with prevalent fracture. Magnetic resonance imaging (MRI) is the gold standard for measuring BMAT, but its use is limited by high costs and low availability. We hypothesized that BMAT could also be accurately quantified using high-resol ...[more]

PMID: 35113175

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Project description: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.

Project description:Osteosarcopenia is a prevalent geriatric disease with a significantly increased risk of adverse outcomes than osteoporosis or sarcopenia alone. Identification of older adults with osteosarcopenia using High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) could allow better clinical decision making. This study aimed to explore the feasibility of HR-pQCT to differentiate osteoporosis, sarcopenia, and osteosarcopenia in older adults, with a primary outcome to derive a model to distinguish older adults with osteosarcopenia from those with low bone mineral density only, and to examine important HR-pQCT parameters associated with osteosarcopenia. This was a cross-sectional study involving 628 community-dwelling Chinese adults aged ≥ 40. Subjects were assessed by dual energy X-ray absorptiometry (DXA) for osteopenia/osteoporosis and sarcopenia using the Asian Working Group for Sarcopenia definition; then grouped into healthy, osteopenia/osteoporosis, sarcopenia, and osteosarcopenia groups. A series of regression analyses and other statistical tests were performed to derive the model. HR-pQCT showed the ability to discriminate older adults with osteosarcopenia from those with osteopenia/osteoporosis only. Cross-validation of our derived model correctly classified 77.0% of the cases with good diagnostic power and showed a sensitivity of 76.0% and specificity of 77.6% (Youden index = 0.54; AUC = 0.79, p < 0.001). Analysis showed trabecular volumetric bone density and cortical periosteal perimeter were important and sensitive parameters in discriminating osteosarcopenia from osteopenia/osteoporosis subjects. These findings demonstrated that HR-pQCT is a viable and effective screening method for differentiating osteosarcopenia from low bone mineral density alone without the need to carry out multiple assessments for osteosarcopenia, especially for case-finding purposes. This could facilitate the decision of a follow-up and the management of these frail older adults to ensure they receive timely therapeutic interventions to minimise the associated risks.

Project description:Purpose of reviewDiabetes mellitus is defined by elevated blood glucose levels caused by changes in glucose metabolism and, according to its pathogenesis, is classified into type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Diabetes mellitus is associated with multiple degenerative processes, including structural alterations of the bone and increased fracture risk. High-resolution peripheral computed tomography (HR-pQCT) is a clinically applicable, volumetric imaging technique that unveils bone microarchitecture in vivo. Numerous studies have used HR-pQCT to assess volumetric bone mineral density and microarchitecture in patients with diabetes, including characteristics of trabecular (e.g. number, thickness and separation) and cortical bone (e.g. thickness and porosity). However, study results are heterogeneous given different imaging regions and diverse patient cohorts.Recent findingsThis meta-analysis assessed T1DM- and T2DM-associated characteristics of bone microarchitecture measured in human populations in vivo reported in PubMed- and Embase-listed publications from inception (2005) to November 2021. The final dataset contained twelve studies with 516 participants with T2DM and 3067 controls and four studies with 227 participants with T1DM and 405 controls. While T1DM was associated with adverse trabecular characteristics, T2DM was primarily associated with adverse cortical characteristics. These adverse effects were more severe at the radius than the load-bearing tibia, indicating increased mechanical loading may compensate for deleterious bone microarchitecture changes and supporting mechanoregulation of bone fragility in diabetes mellitus. Our meta-analysis revealed distinct predilection sites of bone structure aberrations in T1DM and T2DM, which provide a foundation for the development of animal models of skeletal fragility in diabetes and may explain the uncertainty of predicting bone fragility in diabetic patients using current clinical algorithms.

Project description:BackgroundPeripheral quantitative computed tomography (pQCT) can provide information complementary to dual x-ray absorptiometry (DXA), however, there is sparse normative data to enable meaningful clinical interpretation and comparison. This study aimed to develop age-stratified normative data for pQCT-derived bone parameters in Australian men.MethodsParticipants were men (n = 508, age 33-96 yr) from the Geelong Osteoporosis Study. Bone parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 438) of tibial length were acquired using pQCT (XCT 2000, Stratec Medizintechnik, Pforzheim, Germany). Best models of age, height and weight for each parameter were developed and where parameters exhibited variation with age, age decade mean (±SD) values were determined. Scatterplots were used to visualise the relationships between each of the parameters and age, height and weight.ResultsThirteen parameters at tibial and radial sites were correlated with age, height and weight, allowing for their inclusion in multiple linear regression models. A positive association with age was found for total area of the tibia or radius (as appropriate) (mm2) at all sites, trabecular bone area (mm2) at 4% sites, and total bone area (both long bones) (mm2) at 66% sites. A negative association with age was found for cortical density (mg/cm3) and cortical thickness (mm) at both radial and tibial 66% sites, but total density (mg/cm3) at the 66% radial site and total cortical density of both long bones (mg/cm3) at the 66% tibial site only.ConclusionThis study presents normative data for pQCT-derived bone parameters and describes age related associations in a number of these variables. Broadly, parameters of bone area were positively associated with age, whereas parameters associated with bone density and structure were negatively associated with age. These data have the potential to be used in clinical settings when assessing age-related decline in bone health.Mini abstractNormative data for pQCT parameters in Australian men are presented, adjusted for age, height and weight.

Project description:Timelapse imaging using high-resolution peripheral quantitative computed tomography has emerged as a non-invasive method to quantify bone (re)modeling. However, there is no consensus on how to perform the procedure. As part of the ASTEROID phase-2b multicenter trial, we used 29 same-day repeated scans from adults with OI to identify a method that minimized measurement error. We evaluated input image type, registration method, segmentation mask, and for grayscale images various values for the voxel density difference considered formed or resorbed, minimum formation/resorption cluster size, and Gaussian smoothing sigma. We verified the accuracy of our method and then used it on longitudinal scans (baseline, 6, 12, 18, and 24 mo) from 78 participants to assess bone formation and resorption induced by an anabolic (setrusumab) and anti-catabolic (zoledronic acid) treatments as part of the ASTEROID trial. Regardless of image registration method, binary input images resulted in large errors ~13% and ~8% for first- and second-generation scanners, respectively. For the grayscale input images, errors were smaller for 3D compared to matched angle registration. For both scanner generations, a density threshold of 200 mgHA/cm3 combined with Gaussian noise reduction resulted in errors <1%. We verified the method was accurate by showing that similar regions of bone formation and resorption were identified when comparing each scan from the same-day repeated scans with a scan from another timepoint. Timelapse analysis revealed a dose-dependent increase in bone formation and resorption with setrusumab treatment. Zoledronic acid altered bone changes in favor of formation, although no changes reached statistical significance. This study identifies a timelapse method that minimizes measurement error, which can be used in future studies to improve the uniformity of results. This non-invasive imaging biomarker revealed dose dependent bone (re)modeling outcomes from 1 year of setrusumab treatment in adults with OI.

Dataset Information

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography.

Methods

Results

Conclusion

Publications

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography.

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