Osteoporosis and low bone mass are currently estimated to be a major public health threat for almost 44 million U.S. women and men aged 50 and older. While the disorder affects both genders, approximately 80% of those having the condition are women. After menopause and the concomitant decline in estrogen levels, bone undergoes structural changes and reduction in tissue volume density resulting in reduced strength and increased fracture susceptibility. Even though effective treatment is available, the high cost and numerous side effects of antiresorptive and anabolic drugs have spurred the search for alternative therapies. Equally important, however, is that pharmacologic intervention is generally not indicated until subjects have progressed to a level of bone density commensurate with the diagnosis of osteoporosis. It has recently been shown that low-magnitude mechanical stimulation (LMMS) at frequencies of tens of Hertz is osteogenic, presumably via downregulation of the nuclear hormone receptor, PPAR, resulting in preferential differentiation of marrow stromal cells toward the osteoblastic instead of the adipocytic lineage. This competing renewal project seeks to further develop methods for image-based micro-finite-element modeling for quantifying various properties of skeletal mechanical competence, along with improved methods for high-resolution structural magnetic resonance (MR) imaging of cortical and trabecular bone, and measurement of bone marrow composition by MR spectroscopic imaging. The resulting protocol will be applied in a subsequent randomized, double-blinded, translational patient study to evaluate the hypothesis that early postmenopausal women, subjected to a daily 10-minute treatment of LMMS for one year, will show an improvement in trabecular and cortical stiffness and failure strength at the tibia, along with a reduction in vertebral marrow adiposity relative to their placebo-treated peers. The successful completion of the project will provide new insight into the potential for image-based computational biomechanics for monitoring prophylactic intervention.

Public Health Relevance

Osteoporosis and low bone mass are major public health issues affecting a significant portion of older Americans, in particular women after menopause. While effective drug treatment is now available, it is expensive, associated with significant side effects and indicated only at a late stage of the disease at which point it is no longer reversible Mechanical stimulation is a new, entirely noninvasive form of nonpharmacologic intervention, but its effect in terms of conferring bone strength is not known. By evaluating changes in bone mechanical competence in early postmenopausal women undergoing mechanical stimulation via image-based computational biomechanics, this project focuses on prevention rather than treatment.

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-DTCS-U (81))
Program Officer
Lester, Gayle E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
Zhang, Ning; Magland, Jeremy F; Song, Hee Kwon et al. (2015) Registration-based autofocusing technique for automatic correction of motion artifacts in time-series studies of high-resolution bone MRI. J Magn Reson Imaging 41:954-63
Al Mukaddam, Mona; Rajapakse, Chamith S; Bhagat, Yusuf A et al. (2014) Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism. J Clin Endocrinol Metab 99:1236-44
Zhang, Ning; Magland, Jeremy F; Rajapakse, Chamith S et al. (2013) Potential of in vivo MRI-based nonlinear finite-element analysis for the assessment of trabecular bone post-yield properties. Med Phys 40:052303
Zhang, Ning; Magland, Jeremy F; Rajapakse, Chamith S et al. (2013) Assessment of trabecular bone yield and post-yield behavior from high-resolution MRI-based nonlinear finite element analysis at the distal radius of premenopausal and postmenopausal women susceptible to osteoporosis. Acad Radiol 20:1584-91
Rajapakse, Chamith S; Leonard, Mary B; Bhagat, Yusuf A et al. (2012) Micro-MR imaging-based computational biomechanics demonstrates reduction in cortical and trabecular bone strength after renal transplantation. Radiology 262:912-20
Wald, Michael Jeffrey; Magland, Jeremy Franklin; Rajapakse, Chamith Sudesh et al. (2010) Structural and mechanical parameters of trabecular bone estimated from in vivo high-resolution magnetic resonance images at 3 tesla field strength. J Magn Reson Imaging 31:1157-68
Liu, X Sherry; Cohen, Adi; Shane, Elizabeth et al. (2010) Individual trabeculae segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis. J Bone Miner Res 25:1496-505
Liu, X Sherry; Zhang, X Henry; Sekhon, Kiranjit K et al. (2010) High-resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res 25:746-56
Liu, X Sherry; Zhang, X Henry; Rajapakse, Chamith S et al. (2010) Accuracy of high-resolution in vivo micro magnetic resonance imaging for measurements of microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res 25:2039-50
Wehrli, Felix W; Rajapakse, Chamith S; Magland, Jeremy F et al. (2010) Mechanical implications of estrogen supplementation in early postmenopausal women. J Bone Miner Res 25:1406-14

Showing the most recent 10 out of 14 publications