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 #
5R01AR060700-02
Application #
8309194
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
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$519,840
Indirect Cost
$51,139
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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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
Nirody, Jasmine A; Cheng, Karen P; Parrish, Robin M et al. (2015) Spatial distribution of intracortical porosity varies across age and sex. Bone 75:88-95
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
Yang, Haitao; Yu, Andrew; Burghardt, Andrew J et al. (2015) Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using high resolution- peripheral quantitative computed tomography. Int J Rheum Dis :
Bonaretti, S; Carpenter, R D; Saeed, I et al. (2014) Novel anthropomorphic hip phantom corrects systemic interscanner differences in proximal femoral vBMD. Phys Med Biol 59:7819-34
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
Tjong, Willy; Nirody, Jasmine; Burghardt, Andrew J et al. (2014) Structural analysis of cortical porosity applied to HR-pQCT data. Med Phys 41:013701
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
Burghardt, Andrew J; Pialat, Jean-Baptiste; Kazakia, Galateia J et al. (2013) Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography. J Bone Miner Res 28:524-36

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