The high variability in patient skeletal response to drug treatments for osteoporosis presupposes an important clinical question: which patients are likely to benefit from a particular intervention? A few studies have examined the capacity of baseline characteristics to predict skeletal response to therapy, but these studies have been limited to alendronate and have focused on areal bone mineral density (aBMD) changes as an endpoint. Although aBMD is associated with incident hip fracture, it is simply a summary parameter of integrated bone mass, and provides no information about changes in whole bone structure and strength, factors that would lend direct mechanistic insight into differences between therapies, and between individuals. The overarching goal of our proposed study is to understand the factors underlying the variability between individuals and treatments of the effect of anti-resorptive (alendronate and zolendronate) and anabolic (parathyroid hormone-PTH) treatments on proximal femoral whole bone strength. We will accomplish this reanalyzing anonymized QCT scans obtained in three different clinical drug studies: HORIZON (zolendronate), PaTH (PTH, alendronate and combination therapy) and OPTAMISE (PTH after cessation of anti-resropritve treatment). As an endpoint measure, we will employ whole-bone strength assessed by volumetric quantitative computed tomography (vQCT)-based subject specific finite element modeling (FEM). In order to visualize, on a voxel-by voxel basis, the BMD and geometric changes that underlie changes in strength, we will employ voxel-based morphometry (VBM), a neuro-image processing technique adapted by our laboratory to the study of bone. We will use VBM to map changes in bone structure, to relate strength changes to baseline structural features, and we will integrate VBM with the stress, strain fields generated by the FEM in order to relate changes in strength and structure to the distribution of stress, strain and strain energy density at baseline. We believe that our experimental approach will provide novel scientific information along with a set of results that can be translated to clinical practic.

Public Health Relevance

With our study, we aim to develop a better understanding of the response of bone strength to drug treatment. We aim to further the translation of these assessments to the clinic through improvements in methodology for quantitative assessment of the proximal femur with CT imaging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR064140-02
Application #
8706047
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (02))
Program Officer
Lester, Gayle E
Project Start
2013-08-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$278,269
Indirect Cost
$19,538
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