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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (04))
Program Officer
Lester, Gayle E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Langsetmo, Lisa; Peters, Katherine W; Burghardt, Andrew J et al. (2018) Volumetric Bone Mineral Density and Failure Load of Distal Limbs Predict Incident Clinical Fracture Independent HR-pQCT BMD and Failure Load Predicts Incident Clinical Fracture of FRAX and Clinical Risk Factors Among Older Men. J Bone Miner Res 33:1302-1311
Langsetmo, L; Shikany, J M; Burghardt, A J et al. (2018) High dairy protein intake is associated with greater bone strength parameters at the distal radius and tibia in older men: a cross-sectional study. Osteoporos Int 29:69-77
Ensrud, K E; Vo, T N; Burghardt, A J et al. (2018) Weight loss in men in late life and bone strength and microarchitecture: a prospective study. Osteoporos Int 29:1549-1558
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
Ghasem-Zadeh, Ali; Burghardt, Andrew; Wang, Xiao-Fang et al. (2017) Quantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions. Bone 101:206-213
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
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
Yang, Haitao; Yu, Andrew; Burghardt, Andrew J et al. (2017) Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using high resolution- peripheral quantitative computed tomography. Int J Rheum Dis 20:353-362
Heilmeier, Ursula; Hackl, Matthias; Skalicky, Susanna et al. (2016) Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro. J Bone Miner Res 31:2173-2192
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

Showing the most recent 10 out of 24 publications