Publications by authors named "Chamith S Rajapakse"

77 Publications

The effect of age when initiating anti-seizure medication therapy on fragility fracture risk for children with epilepsy.

Bone 2021 May 5;149:115996. Epub 2021 May 5.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

Background: Anti-seizure medication (ASM) is necessary to manage epilepsy and often prescribed to children and adolescents, but can lead to iatrogenic effects, including bone fragility by altering bone metabolism. Disrupting bone metabolism during crucial developmental stages could have a lasting adverse effect on bone health. Therefore, the objective of this propensity score-matched, observational cohort study was to determine if age when initiating ASM therapy across developmental stages (from pre- to post-puberty) for individuals with epilepsy was associated with an increased risk of fragility fracture.

Methods: Data from 01/01/2011 to 12/31/2018 were extracted from Optum Clinformatics® Data Mart. Children aged 4-21 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline and 4-years of follow-up. The primary group of interest included new ASM users (i.e., treatment naïve) with epilepsy. The comparison group, no ASM users without epilepsy, was matched 1:14 to new ASM users with epilepsy for demographics and baseline fracture. To provide a proxy for developmental stages, age was categorized as 4-6 (pre-puberty), 7-10 (early puberty), 11-13 (mid-puberty), 14-17 (late puberty), and 18-21 (post-puberty). Crude incidence rate (IR; per 1000 person years) and IR ratio (IRR and 95% confidence intervals [CI]) were estimated for non-trauma fracture (NTFx) for up to 4-years of follow-up.

Results: Prior to stratifying by age group, the crude NTFx IR (95% CI) of 20.6 (16.5-24.8) for new ASM users with epilepsy (n = 1205) was 34% higher (IRR = 1.34; 95% CI = 1.09-1.66) than the crude NTFx IR (95% CI) of 15.4 (14.4-16.3) for no ASM users without epilepsy. The groups exhibited a different pattern of NTFx incidence with age, with new ASM users showing a more dramatic increase and peaking at 11-13 years, then decreasing with the older age groups. The crude IR and IRR were elevated for new ASM users with epilepsy compared to no ASM users without epilepsy for each age group (10% to 55% higher), but was only statistically significant for 11-13 years (IRR = 1.55; 95% CI = 1.02-2.36).

Conclusions: Children with epilepsy initiating ASM therapy may be vulnerable to fragility fracture, especially when initiating ASM around the time of puberty. Clinicians should be aware of this age-related association and consider age-appropriate adjunct bone fragility therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2021.115996DOI Listing
May 2021

A deep learning system for automated, multi-modality 2D segmentation of vertebral bodies and intervertebral discs.

Bone 2021 Apr 21;149:115972. Epub 2021 Apr 21.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.

Purpose: Fractures in vertebral bodies are among the most common complications of osteoporosis and other bone diseases. However, studies that aim to predict future fractures and assess general spine health must manually delineate vertebral bodies and intervertebral discs in imaging studies for further radiomic analysis. This study aims to develop a deep learning system that can automatically and rapidly segment (delineate) vertebrae and discs in MR, CT, and X-ray imaging studies.

Results: We constructed a neural network to output 2D segmentations for MR, CT, and X-ray imaging studies. We trained the network on 4490 MR, 550 CT, and 1935 X-ray imaging studies (post-data augmentation) spanning a wide variety of patient populations, bone disease statuses, and ages from 2005 to 2020. Evaluated using 5-fold cross validation, the network was able to produce median Dice scores > 0.95 across all modalities for vertebral bodies and intervertebral discs (on the most central slice for MR/CT and on image for X-ray). Furthermore, radiomic features (skewness, kurtosis, mean of positive value pixels, and entropy) calculated from predicted segmentation masks were highly accurate (r ≥ 0.96 across all radiomic features when compared to ground truth). Mean time to produce outputs was <1.7 s across all modalities.

Conclusions: Our network was able to rapidly produce segmentations for vertebral bodies and intervertebral discs for MR, CT, and X-ray imaging studies. Furthermore, radiomic quantities derived from these segmentations were highly accurate. Since this network produced outputs rapidly for these modalities which are commonly used, it can be put to immediate use for radiomic and clinical imaging studies assessing spine health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2021.115972DOI Listing
April 2021

Association of baseline subject characteristics with changes in coronary calcification assessed by F-sodium fluoride PET/CT.

Hell J Nucl Med 2021 Jan-Apr;24(1):45-52. Epub 2021 Apr 20.

Department of Radiology, University of Pennsylvania, 1 Founders Building, MRI Education Center, 3400 Spruce St, Philadelphia, PA 19104, 215-349-8519, Philadelphia, PA.

Objective: The goal of this study was to test if changes in coronary microcalcification over a two year period assessed by fluorine-18-sodium fluoride (F-NaF) positron emission tomography/computed tomography (PET/CT) are associated with baseline subject characteristics.

Subjects And Methods: This prospective study included healthy female (N=8, age 52±10 years, body mass index(BMI) 24±1.7kg/m) and male (N=15, age 50±10 years, BMI 27±2.9kg/m) participants who had F-NaF PET/CT scans taken two years apart. Imaging was performed 90 minutes after intravenous injection of 2.2MBq of F-NaF per kilogram of body weight. The analysis regions were selected on CT images by drawing volumes of interest around the entire heart using a semi-automatic segmentation method.Mean standardize uptake value (SUVmean) and maximum SUV (SUVmax) were calculated in the same regions of the registered PET images. Percent change in SUV between the two time points were correlated against baseline age, BMI, cardiovascular risk factors, and blood chemistry.

Results: In males, percent change in SUVmean over the two year period was positively correlated with baseline BMI (r=0.85, P<0.0001) and systolic blood pressure (r=0.65, P=0.0082). These baseline values were not significantly correlated with SUVmax in either gender.

Conclusion: High BMI is a known risk factor for atherosclerosis. Our data showed that rate of increase in coronary microcalcification over time measured by F-NaF PET/CT is associated with baseline BMI and some clinical risk factors in males. Lack of such associations in females could be due to low sample size (N=8). Further prospective studies are needed to determine if baseline BMI and clinical factors could be used to predict rate of increase in coronary microcalcification which could provide the basis for managing the progression of atherosclerosis in patient-specific manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1967/s002449912305DOI Listing
April 2021

Artificial Intelligence: The Future of Maxillofacial Prognosis and Diagnosis?

J Oral Maxillofac Surg 2021 Feb 26. Epub 2021 Feb 26.

Assistant Professor, Section Chief Penn Presbyterian Hospital, Section Chief Philadelphia Veteran's Affairs Medical Center, Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2021.02.031DOI Listing
February 2021

The Effect of Inflammation on Bone.

Front Physiol 2020 5;11:511799. Epub 2021 Jan 5.

Department of Radiology and Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States.

Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.511799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874051PMC
January 2021

Effect of Low-Intensity Vibration on Bone Strength, Microstructure, and Adiposity in Pre-Osteoporotic Postmenopausal Women: A Randomized Placebo-Controlled Trial.

J Bone Miner Res 2021 Apr 23;36(4):673-684. Epub 2020 Dec 23.

Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.

There has been evidence that cyclical mechanical stimulation may be osteogenic, thus providing opportunities for nonpharmacological treatment of degenerative bone disease. Here, we applied this technology to a cohort of postmenopausal women with varying bone mineral density (BMD) T-scores at the total hip (-0.524 ± 0.843) and spine (-0.795 ± 1.03) to examine the response to intervention after 1 year of daily treatment with 10 minutes of vibration therapy in a randomized double-blinded trial. The device operates either in an active mode (30 Hz and 0.3 g) or placebo. Primary endpoints were changes in bone stiffness at the distal tibia and marrow adiposity of the vertebrae, based on 3 Tesla high-resolution MRI and spectroscopic imaging, respectively. Secondary outcome variables included distal tibial trabecular microstructural parameters and vertebral deformity determined by MRI, volumetric and areal bone densities derived using peripheral quantitative computed tomography (pQCT) of the tibia, and dual-energy X-ray absorptiometry (DXA)-based BMD of the hip and spine. Device adherence was 83% in the active group (n = 42) and 86% in the placebo group (n = 38) and did not differ between groups (p = .7). The mean 12-month changes in tibial stiffness in the treatment group and placebo group were +1.31 ± 6.05% and -2.55 ± 3.90%, respectively (group difference 3.86%, p = .0096). In the active group, marrow fat fraction significantly decreased after 12 months of intervention (p = .0003), whereas no significant change was observed in the placebo group (p = .7; group difference -1.59%, p = .029). Mean differences of the changes in trabecular bone volume fraction (p = .048) and erosion index (p = .044) were also significant, as was pQCT-derived trabecular volumetric BMD (vBMD; p = .016) at the tibia. The data are commensurate with the hypothesis that vibration therapy is protective against loss in mechanical strength and, further, that the intervention minimizes the shift from the osteoblastic to the adipocytic lineage of mesenchymal stem cells. © 2020 American Society for Bone and Mineral Research (ASBMR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4229DOI Listing
April 2021

Magnetic resonance imaging-based partial volume-corrected 18F-sodium fluoride positron emission tomography in the femoral neck.

Nucl Med Commun 2021 Apr;42(4):416-420

Department of Radiology, Hospital of the University of Pennsylvania.

Objectives: 18F-sodium fluoride (NaF) is a radiotracer used in PET that reflects calcium metabolism and osteoblastic activity. In this study, we assessed the construct validity of a novel application of global assessment to measure NaF uptake in the femoral neck as a method of evaluating physiologic changes in osteoblastic metabolism with age.

Methods: Whole-body NaF-PET/computed tomography (CT) images and MRI of 24 male patients with a history of nonmetastatic prostate cancer between the ages of 36 and 82 years (67.8 ± 9.6) were analyzed. A region of interest delineated the entire femoral neck on the PET/CT image to determine the mean standardized uptake value (SUVmean). Correction for the partial volume effect was performed by measuring the volume of inert yellow bone marrow by MRI segmentation. Multiple linear regression was used to assess the relationship of uptake with age and body weight.

Results: The SUVmean with and without partial volume correction decreased with respect to age (P = 0.001 and P = 0.002, respectively). Body weight was not significantly related to any measured PET parameter.

Conclusion: Our results support the use of global NaF uptake with magnetic resonance-derived partial volume correction in the femoral neck. Because osteoblastic metabolism is known to decrease with normal aging, the observed decrease in NaF uptake constitutes evidence for convergent validity, indicating that the proposed methodology likely reflects systemic osteoblastic activity. Future studies of this methodology are warranted in other instances of varying osteoblastic activity such as in metabolic bone diseases and for the evaluation of therapy targeting osteoblastic metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0000000000001344DOI Listing
April 2021

MRI-derived porosity index is associated with whole-bone stiffness and mineral density in human cadaveric femora.

Bone 2021 02 30;143:115774. Epub 2020 Nov 30.

Department of Radiology, University of Pennsylvania, United States of America; Department of Orthopaedic Surgery, University of Pennsylvania, United States of America.

Ultrashort echo time (UTE) magnetic resonance imaging (MRI) measures proton signals in cortical bone from two distinct water pools, bound water, or water that is tightly bound to bone matrix, and pore water, or water that is freely moving in the pore spaces in bone. By isolating the signal contribution from the pore water pool, UTE biomarkers can directly quantify cortical bone porosity in vivo. The Porosity Index (PI) is one non-invasive, clinically viable UTE-derived technique that has shown strong associations in the tibia with μCT porosity and other UTE measures of bone water. However, the efficacy of the PI biomarker has never been examined in the proximal femur, which is the site of the most catastrophic osteoporotic fractures. Additionally, the loads experienced during a sideways fall are complex and the femoral neck is difficult to image with UTE, so the usefulness of the PI in the femur was unknown. Therefore, the aim of this study was to examine the relationships between the PI measure in the proximal cortical shaft of human cadaveric femora specimens compared to (1) QCT-derived bone mineral density (BMD) and (2) whole bone stiffness obtained from mechanical testing mimicking a sideways fall. Fifteen fresh, frozen whole cadaveric femora specimens (age 72.1 ± 15.0 years old, 10 male, 5 female) were scanned on a clinical 3-T MRI using a dual-echo UTE sequence. Specimens were then scanned on a clinical CT scanner to measure volumetric BMD (vBMD) and then non-destructively mechanically tested in a sideways fall configuration. The PI in the cortical shaft demonstrated strong correlations with bone stiffness (r = -0.82, P = 0.0014), CT-derived vBMD (r = -0.64, P = 0.0149), and with average cortical thickness (r = -0.60, P = 0.0180). Furthermore, a hierarchical regression showed that PI was a strong predictor of bone stiffness which was independent of the other parameters. The findings from this study validate the MRI-derived porosity index as a useful measure of whole-bone mechanical integrity and stiffness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769997PMC
February 2021

Total-Body PET Imaging of Musculoskeletal Disorders.

PET Clin 2021 Jan;16(1):99-117

Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Imaging of musculoskeletal disorders, including arthritis, infection, osteoporosis, sarcopenia, and malignancies, is often limited when using conventional modalities such as radiography, computed tomography (CT), and MR imaging. As a result of recent advances in Positron Emission Tomography (PET) instrumentation, total-body PET/CT offers a longer axial field-of-view, higher geometric sensitivity, and higher spatial resolution compared with standard PET systems. This article discusses the potential applications of total-body PET/CT imaging in the assessment of musculoskeletal disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cpet.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684980PMC
January 2021

Imaging Atherosclerosis by PET, With Emphasis on the Role of FDG and NaF as Potential Biomarkers for This Disorder.

Front Physiol 2020 22;11:511391. Epub 2020 Oct 22.

Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.

Molecular imaging has emerged in the past few decades as a novel means to investigate atherosclerosis. From a pathophysiological perspective, atherosclerosis is characterized by microscopic inflammation and microcalcification that precede the characteristic plaque buildup in arterial walls detected by traditional assessment methods, including anatomic imaging modalities. These processes of inflammation and microcalcification are, therefore, prime targets for molecular detection of atherosclerotic disease burden. Imaging with positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) can non-invasively assess arterial inflammation and microcalcification, respectively. FDG uptake reflects glucose metabolism, which is particularly increased in atherosclerotic plaques retaining macrophages and undergoing hypoxic stress. By contrast, NaF uptake reflects the exchange of hydroxyl groups of hydroxyapatite crystals for fluoride producing fluorapatite, a key biochemical step in calcification of atherosclerotic plaque. Here we review the existing literature on FDG and NaF imaging and their respective values in investigating the progression of atherosclerotic disease. Based on the large volume of data that have been introduced to the literature and discussed in this review, it is clear that PET imaging will have a major role to play in assessing atherosclerosis in the major and coronary arteries. However, it is difficult to draw definitive conclusions on the potential role of FDG in investigating atherosclerosis given the vast number of studies with different designs, image acquisition methods, analyses, and interpretations. Our experience in this domain of research has suggested that NaF may be the tool of choice over FDG in assessing atherosclerosis, especially in the setting of coronary artery disease (CAD). Specifically, global NaF assessment appears to be superior in detecting plaques in tissues with high background FDG activity, such as the coronary arteries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.511391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642524PMC
October 2020

Bone microarchitecture in patients undergoing parathyroidectomy for management of secondary hyperparathyroidism.

Bone Rep 2020 Dec 15;13:100297. Epub 2020 Jul 15.

Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

Background: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) leads to complex bone disease, affecting both trabecular and cortical bone, and increased fracture risk. Optimal assessment of bone in patients with CKD is yet to be determined. High-resolution magnetic resonance imaging (MRI) can provide three-dimensional assessment of bone microarchitecture, as well as determination of mechanical strength with finite element analysis (FEA).

Methods: We conducted a single-centre, cross-sectional study to determine bone microarchitecture with MRI in CKD patients with SHPT undergoing parathyroidectomy. Within two weeks of surgery, MRI was performed at the distal tibia and biochemical markers of SHPT (parathyroid hormone [PTH] and alkaline phosphatase [ALP]) were collected. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Correlation of MRI findings of bone was made with biochemical markers.

Results: Twenty patients with CKD (15 male, 5 female) underwent MRI at the time of parathyroidectomy (16 on dialysis, 3 with functioning kidney transplant, one pre-dialysis with CKD stage 5). Median PTH at the time of surgery was 138.5 pmol/L [39.6-186.7 pmol/L]. MRI parameters in patients were consistent with trabecular deterioration, with erosion index (EI) 1.01 ± 0.3, and trabecular bone volume (BV/TV) 10.8 ± 2.9%, as well as poor trabecular network integrity with surface-to-curve ratio (S/C) 5.4 ± 2.3. There was also evidence of reduced cortical thickness, with CTh 2.698 ± 0.630 mm, and FEA demonstrated overall poor bone mechanical strength with mean elastic modulus of 2.07 ± 0.44.

Conclusion: Patients with severe SHPT requiring parathyroidectomy have evidence of significant changes in bone microarchitecture with trabecular deterioration, low trabecular and cortical bone volume, and reduced mechanical competence of bone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2020.100297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393533PMC
December 2020

Near infrared spectroscopic assessment of loosely and tightly bound cortical bone water.

Analyst 2020 May 28;145(10):3713-3724. Epub 2020 Apr 28.

Department of Bioengineering, Temple University, USA.

Water is an important component of bone and plays a key role in its mechanical and structural integrity. Water molecules in bone are present in different locations, including loosely or tightly bound to the matrix and/or mineral (biological apatite) phases. Identification of water location and interactions with matrix components impact bone function but have been challenging to assess. Here, we used near infrared (NIR) spectroscopy to identify loosely and tightly bound water present in cortical bone. In hydrated samples, NIR spectra have two primary water absorption bands at frequencies of ∼5200 and 7000 cm. Using lyophilization and hydrogen-deuterium exchange assays, we showed that these absorption bands are primarily associated with loosely bound bone water. Using further demineralization assays, thermal denaturation, and comparison to standards, we found that these absorption bands have underlying components associated with water molecules tightly bound to bone. In dehydrated samples, the peak at ∼5200 cm was assigned to a combination of water tightly bound to collagen and to mineral, whereas the peak at 7000 cm was exclusively associated with tightly bound mineral water. We also found significant positive correlations between the NIR mineral absorption bands and the mineral content as determined by an established mid infrared spectroscopic parameter, phosphate/amide I. Moreover, the NIR water data showed correlation trends with tissue mineral density (TMD) in cortical bone tissues. These observations reveal the ability of NIR spectroscopy to non-destructively identify loosely and tightly bound water in bone, which could have further applications in biomineralization and biomedical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9an02491cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301914PMC
May 2020

Assessment of femoral neck bone metabolism using F-sodium fluoride PET/CT imaging.

Bone 2020 07 8;136:115351. Epub 2020 Apr 8.

Departments of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Departments of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Standard of care metabolic bone disease assessment relies on changes to bone quantity, which can only be detected after structural changes occur.

Purpose: To investigate the usefulness of Bone Metabolism Score (BMS), derived from fluorine 18 labeled sodium fluoride (F-NaF) PET/CT imaging as a biomarker of localized metabolic changes at the femoral neck.

Methods: In this retrospective study, 139 participants (68 females and 71 males, ages 21-75 years) that had undergone F-NaF PET/CT were included. BMS was calculated as the ratio of standard uptake value (SUV) in the bone region to that of the total region. Correlations and linear regressions of BMS with age, CT-derived bone mineral density (BMD), body mass index (BMI), height, and weight were conducted. Differences in BMS between women younger and older than the age of 50 years were assessed. Inter- and intra-operator reproducibility was evaluated by coefficient of variation (CV) and intra-class correlation coefficient (ICC).

Results: Among females, age was negatively correlated with left and right whole BMS (5.61% and 4.90% drop in BMS per decade of life) and left and right cortical BMS (10.50% and 10.09% drop in BMS per decade of life). BMS of women older than 50 years was lower than BMS of women younger than 50 years (P < .0001). Among males, age was negatively correlated with left and right whole BMS (4.29% and 4.25% drop in BMS per decade of life) and left and right cortical BMS (9.13% and 10.30% drop in BMS per decade of life). BMD was positively correlated with whole (r = 0.80, P < .0001) and cortical (r = 0.92, P < .0001) BMS.

Conclusions: BMS could provide functional insight regarding bone metabolism in the femoral neck to complement bone health status assessed through conventional structural imaging. The methodology described herein could be potentially useful for assessing hip fracture risk in individuals when BMD tests provide borderline determination of bone disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246165PMC
July 2020

Assessment of the multifactorial causes of atypical femoral fractures using a novel multiscale finite element approach.

Bone 2020 06 12;135:115318. Epub 2020 Mar 12.

Department of Mechanical Engineering, Villanova University, Villanova, PA, USA. Electronic address:

Atypical femoral fracture (AFF), which is a low energy fracture in the subtrochanteric or diaphysis region of the femur, has multifactorial causes that span macro- to microscale mechanisms including femoral geometry, cortical bone composition and structure. However, the extent of individual and combined influence of these factors on AFF is still not well understood. As a result, the aim of this study is to develop a multiscale fracture mechanics-based finite element modeling framework that is capable of quantifying the individual and combined influence of macroscale femoral geometrical properties as well as cortical bone microscale material properties and structure on AFF. In this study, three different femoral geometries with two different cortical bone microstructures, and two different material property distributions were investigated by first determining the critical AFF locations in the femur using macroscale stress analysis and then performing coupled macro-microscale fracture simulations. The simulation results showed that femoral geometry led to substantial differences in crack growth independent of cortical microstructure and tissue level material properties. The results suggest that multiple femoral geometrical properties, including neck-shaft angle and curvature, may contribute to the fracture behavior at AFF sites rather than a single macroscale geometrical feature. Osteonal area had a significant effect on microcrack propagation at AFF sites independent of microscale material property distribution and femoral geometry. In addition, cortical bone tissue level material heterogeneity improved the fracture resistance independent of femoral geometry and cortical microstructure. In summary, the computational approach developed in this study identified the individual, combined, and relative influence of multiscale factors on AFF risk. The new framework developed in this study could help identify the governing multiscale mechanisms of AFF and bring additional insight into the possible association of long-term bisphosphate treatment with AFF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115318DOI Listing
June 2020

MRI-based assessment of proximal femur strength compared to mechanical testing.

Bone 2020 04 9;133:115227. Epub 2020 Jan 9.

Department of Radiology, New York University, United States of America.

Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora. Imaging was conducted on a 3-Tesla MRI scanner using two sequences: one balanced steady-state free precession sequence with 300 μm isotropic voxel size and one spoiled gradient echo with anisotropic voxel size of 234 × 234 × 1500 μm. Femora were dissected free of soft-tissue and 4350-ohm strain-gauges were securely applied to surfaces at the femoral shaft, inferior neck, greater trochanter, and superior neck. Cadavers were mechanically tested with a hydraulic universal test frame to simulate loading in a sideways fall orientation. Sideways fall forces were simulated on MRI-based finite element meshes and bone stiffness, failure force, and force for plastic deformation were computed. Simulated bone strength metrics from the 300 μm isotropic sequence showed strong agreement with experimentally obtained values of bone strength, with stiffness (r = 0.88, p = 0.0002), plastic deformation point (r = 0.89, p < 0.0001), and failure force (r = 0.92, p < 0.0001). The anisotropic sequence showed similar trends for stiffness, plastic deformation point, and failure force (r = 0.68, 0.70, 0.84; p = 0.02, 0.01, 0.0006, respectively). Surface strain-gauge measurements showed moderate to strong agreement with simulated magnitude strain values at the greater trochanter, superior neck, and inferior neck (r = -0.97, -0.86, 0.80; p ≤0.0001, 0.003, 0.03, respectively). The findings from this study support the use of MRI-based FE analysis of the hip to reliably predict the mechanical competence of the human femur in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096175PMC
April 2020

F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification.

Eur J Nucl Med Mol Imaging 2020 07 16;47(7):1678-1687. Epub 2019 Nov 16.

Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.

Aims: To investigate the benefit of utilizing F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention.

Methods And Results: This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUV; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUV could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUV) did not differ between patients and controls. SUV correlated with age and BMI among females (age, partial R = 0.16, P = 0.001; BMI, partial R = 0.12, P = 0.004) and males (age, partial R = 0.28, P < 0.0001; BMI, partial R = 0.22, P < 0.0001).

Conclusion: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUV, but were not sensitive enough to predict patient status. SUV values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries.

Trial Registration: ClinicalTrials.gov (NCT01724749).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-019-04590-3DOI Listing
July 2020

MRI-derived bone porosity index correlates to bone composition and mechanical stiffness.

Bone Rep 2019 Dec 26;11:100213. Epub 2019 Jun 26.

Department of Radiology, University of Pennsylvania, United States of America.

The MRI-derived porosity index (PI) is a non-invasively obtained biomarker based on an ultrashort echo time sequence that images both bound and pore water protons in bone, corresponding to water bound to organic collagenous matrix and freely moving water, respectively. This measure is known to strongly correlate with the actual volumetric cortical bone porosity. However, it is unknown whether PI may also be able to directly quantify bone organic composition and/or mechanical properties. We investigated this in human cadaveric tibiae by comparing PI values to near infrared spectral imaging (NIRSI) compositional data and mechanical compression data. Data were obtained from a cohort of eighteen tibiae from male and female donors with a mean ± SD age of 70 ± 21 years. Biomechanical stiffness in compression and NIRSI-derived collagen and bound water content all had significant inverse correlations with PI ( = -0.79, -0.73, and -0.95 and  = 0.002, 0.007, and <0.001, respectively). The MRI-derived bone PI alone was a moderate predictor of bone stiffness (  = 0.63,  = 0.002), and multivariate analyses showed that neither cortical bone cross-sectional area nor NIRSI values improved bone stiffness prediction compared to PI alone. However, NIRSI-obtained collagen and water data together were a moderate predictor of bone stiffness (R = 0.52,  = 0.04). Our data validates the MRI-derived porosity index as a strong predictor of organic composition of bone and a moderate predictor of bone stiffness, and also provides preliminary evidence that NIRSI measures may be useful in future pre-clinical studies on bone pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2019.100213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660551PMC
December 2019

Environmentally-Controlled Near Infrared Spectroscopic Imaging of Bone Water.

Sci Rep 2019 07 15;9(1):10199. Epub 2019 Jul 15.

Department of Bioengineering, Temple University, Philadelphia, USA.

We have designed an environmentally-controlled chamber for near infrared spectroscopic imaging (NIRSI) to monitor changes in cortical bone water content, an emerging biomarker related to bone quality assessment. The chamber is required to ensure repeatable spectroscopic measurements of tissues without the influence of atmospheric moisture. A calibration curve to predict gravimetric water content from human cadaveric cortical bone was created using NIRSI data obtained at six different lyophilization time points. Partial least squares (PLS) models successfully predicted bone water content that ranged from 0-10% (R = 0.96, p < 0.05, root mean square error of prediction (RMSEP) = 7.39%), as well as in the physiologic range of 4-10% of wet tissue weight (R = 0.87, p < 0.05, RMSEP = 14.5%). Similar results were obtained with univariate and bivariate regression models for prediction of water in the 0-10% range. Further, we identified two new NIR bone absorbances, at 6560 cm and 6688 cm, associated with water and collagen respectively. Such data will be useful in pre-clinical studies that investigate changes in bone quality with disease, aging and with therapeutic use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-45897-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629628PMC
July 2019

A multi-imaging modality study of bone density, bone structure and the muscle - bone unit in end-stage renal disease.

Bone 2019 10 31;127:271-279. Epub 2019 May 31.

Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.

End stage renal disease (ESRD) is associated with sarcopenia and skeletal fragility. The objectives of this cross-sectional study were to (1) characterize body composition, bone mineral density (BMD) and bone structure in hemodialysis patients compared with controls, (2) assess whether DXA areal BMD (aBMD) correlates with peripheral quantitative CT (pQCT) measures of volumetric BMD (vBMD), cortical dimensions and MRI measures of trabecular microarchitecture, and (3) determine the magnitude of bone deficits in ESRD after adjustment for muscle mass. Thirty ESRD participants, ages 25 to 64 years, were compared with 403 controls for DXA and pQCT outcomes and 104 controls for MRI outcomes; results were expressed as race- and sex- specific Z-scores relative to age. DXA appendicular lean mass index (ALMI kg/m) and total hip, femoral neck, ultradistal and 1/3rd radius aBMD were significantly lower in ESRD, vs. controls (all p < 0.01). pQCT trabecular vBMD (p < 0.01), cortical vBMD (p < 0.001) and cortical thickness (due to a greater endosteal circumference, p < 0.02) and MRI measures of trabecular number, trabecular thickness, and whole bone stiffness were lower (all p < 0.01) in ESRD, vs. controls. ALMI was positively associated with total hip, femoral neck, ultradistal radius and 1/3rd radius aBMD and with tibia cortical thickness (R = 0.46 to 0.64). Adjustment for ALMI significantly attenuated bone deficits at these sites: e.g. mean femoral neck aBMD was 0.79 SD lower in ESRD, compared with controls and this was attenuated to 0.33 with adjustment for ALMI. In multivariate models within the dialysis participants, pQCT trabecular vBMD and cortical area Z-scores were significant and independently (all p < 0.02) associated with DXA femoral neck, total hip, and ultradistal radius aBMD Z-scores. Cortical vBMD (p = 0.01) and cortical area (p < 0.001) Z-scores were significantly and independently associated with 1/3rd radius areal aBMD Z-scores (R = 0.62). These data demonstrate that DXA aBMD captures deficits in trabecular and cortical vBMD and cortical area. The strong associations with ALMI, as an index of skeletal muscle, highlight the importance of considering the role of sarcopenia in skeletal fragility in patients with ESRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2019.05.022DOI Listing
October 2019

A Novel MRI Tool for Evaluating Cortical Bone Thickness of the Proximal Femur.

Bull Hosp Jt Dis (2013) 2019 Mar;77(2):115-121

Background: Osteoporotic hip fractures heavily cost the health care system. Clinicians and patients can benefit from improved tools to assess bone health. Herein, we aim to develop a three-dimensional magnetic resonance imaging (MRI) method to assess cortical bone thickness and assess the ability of the method to detect regional changes in the proximal femur.

Methods: Eighty-nine patients underwent hip magnetic resonance imaging. FireVoxel and 3DSlicer were used to generate three-dimensional proximal femur models. ParaView was used to define five regions: head, neck, greater trochanter, intertrochanteric region, and subtrochanteric region. Custom software was used to calculate the cortical bone thickness and generate a color map of the proximal femur. Mean cortical thickness values for each region were calculated. Statistical t-tests were performed to evaluate differences in cortical thickness based on proximal femur region. Measurement reliability was evaluated using coefficient of variation, intraclass correlation coefficients, and overlap metrics.

Results: Three-dimensional regional cortical thickness maps for all subjects were generated. The subtrochanteric region was found to have the thickest cortical bone and the femoral head had the thinnest cortical bone. There were statistically significant differences between regions (p < 0.01) for all possible comparisons.

Conclusions: Cortical bone is an important contributor to bone strength, and its thinning results in increased hip fracture risk. We describe the development and measurement reproducibility of an MRI tool permitting assessment of proximal femur cortical thickness. This study represents an important step toward longitudinal clinical trials interested in monitoring the effectiveness of drug therapy on proximal femur cortical thickness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336874PMC
March 2019

Influence of bone lesion location on femoral bone strength assessed by MRI-based finite-element modeling.

Bone 2019 05 7;122:209-217. Epub 2019 Mar 7.

New York University, New York, NY, United States of America.

Currently, clinical determination of pathologic fracture risk in the hip is conducted using measures of defect size and shape in the stance loading condition. However, these measures often do not consider how changing lesion locations or how various loading conditions impact bone strength. The goal of this study was to determine the impact of defect location on bone strength parameters in both the sideways fall and stance-loading conditions. We recruited 20 female subjects aged 48-77 years for this study and performed MRI of the proximal femur. Using these images, we simulated 10-mm pathologic defects in greater trochanter, superior, middle, and inferior femoral head, superior, middle, and inferior femoral neck, and lateral, middle, and medial proximal diaphysis to determine the effect of defect location on change in bone strength by performing finite element analysis. We compared the effect of each osteolytic lesion on bone stiffness, strength, resilience, and toughness. For the sideways fall loading, defects in the inferior femoral head (12.21%) and in the greater trochanter (6.43%) resulted in the greatest overall reduction in bone strength. For the stance loading, defects in the mid femoral head (-7.91%) and superior femoral head (-7.82%) resulted in the greatest overall reduction in bone strength. Changes in stiffness, yield force, ultimate force, resilience, and toughness were not found to be significantly correlated between the sideways fall and stance-loading for the majority of defect locations, suggesting that calculations based on the stance-loading condition are not predictive of the change in bone strength experienced in the sideways fall condition. While stiffness was significantly related to yield force (R > 0.82), overall force (R > 0.59), and resilience (R > 0.55), in both, the stance-loading and sideways fall conditions for most defect locations, stiffness was not significantly related to toughness. Therefore, structure-dependent measure such as stiffness may not fully explain the post-yield measures, which depend on material failure properties. The data showed that MRI-based models have the sensitivity to determine the effect of pathologic lesions on bone strength.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2019.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486650PMC
May 2019

Evolving Role of MR Imaging and PET in Assessing Osteoporosis.

PET Clin 2019 Jan 24;14(1):31-41. Epub 2018 Oct 24.

Department of Radiology, University of Pennsylvania, 3400 Spruce Street, MRI Education Center, 1 Founders Building, 253 South 45th Street, Philadelphia, PA 19104, USA. Electronic address:

An imbalance in bone remodeling results in many metabolic bone diseases, such as osteoporosis. fluorine-18 sodium fluoride PET imaging allows the assessment of bone remodeling process in a anatomy specific manner. On the other hand structural imaging modalities such as MRI can now generate high resolution images of bone including the trabecular and cortical microstructure. Molecular (functional) imaging with PET in conjunction with structural imaging has the potential to improve the way metabolic bone diseases are managed in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cpet.2018.08.007DOI Listing
January 2019

Diagnosis and Monitoring of Osteoporosis With F-Sodium Fluoride PET: An Unavoidable Path for the Foreseeable Future.

Semin Nucl Med 2018 Nov 3;48(6):535-540. Epub 2018 Sep 3.

University of Pennsylvania, Philadelphia, PA.

The prevalence of metabolic bone diseases particularly osteoporosis and its precursor, osteopenia, continue to grow as serious global health issues today. On a worldwide perspective, 200million people suffer from osteoporosis and in 2005, over 2million fracture incidents were estimated due to osteoporosis in the United States. Currently, osteoporosis and other metabolic bone diseases are evaluated primarily through dual energy X-ray absorptiometry, and rarely by bone biopsy with tetracycline labeling or Technetium-99m (Tc) based bone scintigraphy. Deficiencies in these methods have prompted the use of more precise methods of assessment. This review highlights the use of F-sodium fluoride (NaF) with PET (NaF-PET), NaF-PET/CT, or NaF-PET/MRI in the evaluation of osteoporosis and osteopenia in the lumbar spine and hip. This imaging modality provides a molecular perspective with respect to the underlying metabolic alterations that lead to osseous disorders by measuring bone turnover through standardized uptake values. Its sensitivity and ability to examine the entire skeletal system make it a more superior imaging modality compared to standard structural imaging techniques. Further research is needed to determine its accuracy in reflecting the efficacy of therapeutic interventions in metabolic bone diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.semnuclmed.2018.07.007DOI Listing
November 2018

Artificial Intelligence Applied to Osteoporosis: A Performance Comparison of Machine Learning Algorithms in Predicting Fragility Fractures From MRI Data.

J Magn Reson Imaging 2019 04 25;49(4):1029-1038. Epub 2018 Sep 25.

New York University School of Medicine, New York, New York, USA.

Background: A current challenge in osteoporosis is identifying patients at risk of bone fracture.

Purpose: To identify the machine learning classifiers that predict best osteoporotic bone fractures and, from the data, to highlight the imaging features and the anatomical regions that contribute most to prediction performance.

Study Type: Prospective (cross-sectional) case-control study.

Population: Thirty-two women with prior fragility bone fractures, of mean age = 61.6 and body mass index (BMI) = 22.7 kg/m , and 60 women without fractures, of mean age = 62.3 and BMI = 21.4 kg/m . Field Strength/ Sequence: 3D FLASH at 3T.

Assessment: Quantitative MRI outcomes by software algorithms. Mechanical and topological microstructural parameters of the trabecular bone were calculated for five femoral regions, and added to the vector of features together with bone mineral density measurement, fracture risk assessment tool (FRAX) score, and personal characteristics such as age, weight, and height. We fitted 15 classifiers using 200 randomized cross-validation datasets. Statistical Tests: Data: Kolmogorov-Smirnov test for normality. Model Performance: sensitivity, specificity, precision, accuracy, F1-test, receiver operating characteristic curve (ROC). Two-sided t-test, with P < 0.05 for statistical significance.

Results: The top three performing classifiers are RUS-boosted trees (in particular, performing best with head data, F1 = 0.64 ± 0.03), the logistic regression and the linear discriminant (both best with trochanteric datasets, F1 = 0.65 ± 0.03 and F1 = 0.67 ± 0.03, respectively). A permutation of these classifiers comprised the best three performers for four out of five anatomical datasets. After averaging across all the anatomical datasets, the score for the best performer, the boosted trees, was F1 = 0.63 ± 0.03 for All-features dataset, F1 = 0.52 ± 0.05 for the no-MRI dataset, and F1 = 0.48 ± 0.06 for the no-FRAX dataset. Data Conclusion: Of many classifiers, the RUS-boosted trees, the logistic regression, and the linear discriminant are best for predicting osteoporotic fracture. Both MRI and FRAX independently add value in identifying osteoporotic fractures. The femoral head, greater trochanter, and inter-trochanter anatomical regions within the proximal femur yielded better F1-scores for the best three classifiers.

Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1029-1038.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.26280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340101PMC
April 2019

Micro-Finite Element Analysis of the Proximal Femur on the Basis of High-Resolution Magnetic Resonance Images.

Curr Osteoporos Rep 2018 12;16(6):657-664

Department of Radiology, New York University, 426 1st Avenue, New York, NY, 10010, USA.

Purpose Of Review: Hip fractures have catastrophic consequences. The purpose of this article is to review recent developments in high-resolution magnetic resonance imaging (MRI)-guided finite element analysis (FEA) of the hip as a means to determine subject-specific bone strength.

Recent Findings: Despite the ability of DXA to predict hip fracture, the majority of fractures occur in patients who do not have BMD T scores less than - 2.5. Therefore, without other detection methods, these individuals go undetected and untreated. Of methods available to image the hip, MRI is currently the only one capable of depicting bone microstructure in vivo. Availability of microstructural MRI allows generation of patient-specific micro-finite element models that can be used to simulate real-life loading conditions and determine bone strength. MRI-based FEA enables radiation-free approach to assess hip fracture strength. With further validation, this technique could become a potential clinical tool in managing hip fracture risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11914-018-0481-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234089PMC
December 2018

Quantitative evaluation of normal spinal osseous metabolism with 18F-NaF PET/CT.

Nucl Med Commun 2018 Oct;39(10):945-950

Departments of Radiology.

Objective: The aim of this study was to describe osseous metabolic activity with respect to age and weight in the spine as expressed through fluorine-18-sodium fluoride (F-NaF) uptake in a healthy male population.

Participants And Methods: Whole-body F-NaF PET/CT scans of healthy male participants (22-71 years, 50-145 kg, n=47) were analysed using a global assessment methodology to derive the mean standardized uptake values (SUVmean). Individual regions of the spine (cervical, thoracic and lumbar) along with the aggregate whole spine were assessed and compared as potential functions of age and body weight.

Results: Older participants did not have higher F-NaF uptake than younger participants (whole spine, P=0.93; cervical, P=0.12, thoracic, P=0.93; lumbar, P=0.42), whereas increasing body weight was associated with greater tracer uptake (whole spine P=0.003; cervical P=0.01; thoracic P=0.002; lumbar P=0.004). Both the thoracic (average SUVmean=4.864±1.338) and lumbar (average SUVmean=4.939±1.284) spines had significantly elevated (P≤0.0001) uptake compared with the cervical spine (average SUVmean=3.969±1.024).

Conclusion: We assessed the metabolic activity of the spine's osseous tissues with F-NaF PET using a global assessment approach in healthy men. Our study provides evidence of differences in spinal metabolism as related to weight, but not age. Our study offers a foundation for future larger studies in symptomatic populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0000000000000891DOI Listing
October 2018

Changes in bone microarchitecture following kidney transplantation-Beyond bone mineral density.

Clin Transplant 2018 09 2;32(9):e13347. Epub 2018 Aug 2.

Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

Bone disease in kidney transplant recipients (KTRs) is characterized by bone mineral density (BMD) loss but bone microarchitecture changes are poorly defined. In this prospective cohort study, we evaluated bone microarchitecture using non-invasive imaging modalities; high-resolution magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DXA), and the trabecular bone score (TBS) following kidney transplantation. Eleven KTRs (48.3 ± 11.2 years) underwent MRI (tibia), pQCT (radius) and DXA at baseline and 12 months post-transplantation. Transiliac bone biopsies, performed at transplantation, showed 70% of patients with high/normal bone turnover. Compared with baseline, 12-month MRI showed deterioration in indices of trabecular network integrity-surface to curve ratio (S/C; -15%, P = 0.03) and erosion index (EI; +19%, P = 0.01). However, cortical area increased (+10.3%, P = 0.04), with a non-significant increase in cortical thickness (CtTh; +7.8%, P = 0.06). At 12 months, parathyroid hormone values (median 10.7 pmol/L) correlated with improved S/C (r = 0.75, P = 0.009) and EI (r = -0.71, P = 0.01) while osteocalcin correlated with CtTh (r = 0.72, P = 0.02) and area (r = 0.70, P = 0.02). TBS decreased from baseline (-5.1%, P = 0.01) with no significant changes in BMD or pQCT. These findings highlight a post-transplant deterioration in trabecular bone quality detected by MRI and TBS, independent of changes in BMD, underlining the potential utility of these modalities in evaluating bone microarchitecture in KTRs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.13347DOI Listing
September 2018

The reproducibility of measuring trabecular bone parameters using a commercially available high-resolution magnetic resonance imaging approach: A pilot study.

Bone Rep 2018 Jun 26;8:180-186. Epub 2018 Apr 26.

Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.

Bone imaging is currently the best non-invasive way to assess changes to bone associated with aging or chronic disease. However, common imaging techniques such as dual energy x-ray absorptiometry are associated with limitations. Magnetic resonance imaging (MRI) is a radiation-free technique that can measure bone microarchitecture. However, published MRI bone assessment protocols use specialized MRI coils and sequences and therefore have limited transferability across institutions. We developed a protocol on a Siemens 3 Tesla MRI machine, using a commercially available coil (Siemens 15 CH knee coil), and manufacturer supplied sequences to acquire images at the tibia. We tested the reproducibility of the FSE and the GE Axial sequences and hypothesized that both would generate reproducible trabecular bone parameters. Eight healthy adults (age 25.5 ± 5.4 years) completed three measurements of each MRI sequence at the tibia. Each of the images was processed for 8 different bone parameters (such as volumetric bone volume fraction). We computed the coefficient of variation (CV) and intraclass correlation coefficients (ICC) to assess reproducibility and reliability. Both sequences resulted in trabecular parameters that were reproducible (CV <5% for most) and reliable (ICC >80% for all). Our study is one of the first to report that a commercially available MRI protocol can result in reproducible data, and is significant as MRI may be an accessible method to measure bone microarchitecture in clinical or research environments. This technique requires further testing, including validation and evaluation in other populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2018.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020268PMC
June 2018

Magnetic resonance imaging based assessment of bone microstructure as a non-invasive alternative to histomorphometry in patients with chronic kidney disease.

Bone 2018 09 31;114:14-21. Epub 2018 May 31.

Departments of Radiology and Orthopaedic Surgery, University of Pennsylvania, PA, USA.

Background: Chronic kidney disease (CKD) adversely affects bone microarchitecture and increases fracture risk. Historically, bone biopsy has been the 'gold standard' for evaluating renal bone disease but is invasive and infrequently performed. High-resolution magnetic resonance imaging (MRI) quantifies bone microarchitecture noninvasively. In patients with CKD, it has not been compared with results derived from bone biopsy or with imaging using dual energy X-ray absorptiometry (DXA).

Methods: Fourteen patients with end-stage kidney disease (ESKD) underwent MRI at the distal tibia, bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA; hip and spine) and transiliac bone biopsies with histomorphometry and microcomputed tomography (micro-CT). All patients had biomarkers of mineral metabolism. Associations were determined by Spearman's or Pearson's rank correlation coefficients.

Results: MRI indices of trabecular network integrity, surface to curve ratio (S/C) and erosion index (EI), correlated to histomorphometric trabecular bone volume (S/C r = 0.85, p = 0.0003; EI r = -0.82, p = 0.001), separation (S/C r = -0.58, p = 0.039; EI r = 0.79, p = 0.0012) and thickness (S/C, r = 0.65, p = 0.017). MRI EI and trabecular thickness (TbTh) also correlated to micro-CT trabecular separation (EI r = 0.63, p = 0.02; TbTh r = -0.60, p = 0.02). Significant correlations were observed between histomorphometric mineralization and turnover indices and various MRI parameters. MRI-derived trabecular parameters were also significantly related to femoral neck BMD.

Conclusions: This study highlights the heterogeneity of bone microarchitecture at differing skeletal sites. MRI demonstrates significant, relevant associations to important bone biopsy and DXA indices and warrants further investigation to assess its potential to non-invasively evaluate changes in bone structure and quality over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2018.05.029DOI Listing
September 2018

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

Am J Nephrol 2018 23;47(6):376-384. Epub 2018 May 23.

Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.

Background: Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis).

Methods: Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients.

Results: By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers.

Conclusions: Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000489671DOI Listing
November 2019