Over the last decade, quantitative computed tomography (QCT) and volumetric QCT (vQCT) images have become important sources of quantitative information on cortical and trabecular bone density, bone geometry and whole bone strength in the central skeleton. Compartmental bone micro-architecture and strength in the peripheral skeleton are being obtained using newly deployed high-resolution peripheral QCT (HR-pQCT) scanners. Although these approaches are in wide use, their inherent value as clinical research tools will depend on two major factors: (i) the ability to seamlessly employ them in the multi-center setting and (ii) the ability to distill fundamental information on pathophysiology and treatment efficacy through """"""""apples to apples"""""""" comparisons of the cohort studies and pharmacologic trials done thus far, a process hindered by the use of multiple scanner types and image analysis platforms. To address these two basic issues, we propose an innovative research program to establish metrics for standardization of vQCT and HR-pQCT acquisitions for future multi-center studies, as well as to provide standardized skeletal density and structural metrics to provide a basis for direct comparison across multiple cohort studies and clinical trials. This work will be carried out at UCSF under the joint direction of Drs Lang and Burghardt and at the Mayo Clinic under the leadership of Dr. Khosla and Dr. Keyak at UCI. This research program is embodied in the following specific aims:
Specific Aim 1 : Development of metrics to standardize QCT and HRpQCT acquisitions and analysis in multicenter studies.
Specific Aim 2 : Development of open-source image analysis metrics for vQCT incorporated as a plug-in NIH supported programs such as MIPAV.

Public Health Relevance

An image-based surrogate for skeletal strength is essential to future clinical development of osteoporosis therapeutics;our project addresses this fundamental problem by adapting vQCT and HR-pQCT imaging to the multi-center environment inherent to clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR060700-04
Application #
8719736
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (04))
Program Officer
Lester, Gayle E
Project Start
2011-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
$444,230
Indirect Cost
$59,550
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Carballido-Gamio, Julio; Bonaretti, Serena; Kazakia, Galateia J et al. (2017) Statistical Parametric Mapping of HR-pQCT Images: A Tool for Population-Based Local Comparisons of Micro-Scale Bone Features. Ann Biomed Eng 45:949-962
Bonaretti, S; Vilayphiou, N; Chan, C M et al. (2017) Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training. Osteoporos Int 28:245-257
Bonaretti, S; Majumdar, S; Lang, T F et al. (2017) The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions. Osteoporos Int 28:2115-2128
Boutroy, Stephanie; Khosla, Sundeep; Sornay-Rendu, Elisabeth et al. (2016) Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T-Score: An International Multicenter Study. J Bone Miner Res 31:1158-66
Okazaki, Narihiro; Burghardt, Andrew J; Chiba, Ko et al. (2016) Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD. Bone Rep 5:312-319
Heilmeier, U; Carpenter, D R; Patsch, J M et al. (2015) Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures. Osteoporos Int 26:1283-93
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Kazakia, Galateia J; Tjong, Willy; Nirody, Jasmine A et al. (2014) The influence of disuse on bone microstructure and mechanics assessed by HR-pQCT. Bone 63:132-40
Carpenter, R Dana; Saeed, Isra; Bonaretti, Serena et al. (2014) Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms. Med Eng Phys 36:1225-32

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