The chief clinical manifestation of osteoporosis is the occurrence of fractures. Most'osteoporotic fractures oc- cur at skeletal locations rich in trabecular bone. Prevailing among these are the vertebrae, wrist and proximal femur. There is now strong evidence that the loss of bone mass is accompanied by a decline in the trabecular bone network's structural integrity. The impaired mechanical competence secondary to gonadal steroid de- pletion is largely due to topological changes in the bone's architectural make-up, chatacterized by fenestra- tion of trabecular plates resulting in their conversion to rods, which eventually become disconnected. The in- vestigators have provided in vivo imaging evidence in previous cycles of this ongoing project in support of such an etiology. Complementing antiresorptive treatment, new therapies have recently become available to treat the devastating consequences of severe bone loss with bone-forming (i.e. anabolic) drugs. It is not clear, however, whether such therapies are, in fact, able to reverse the disintegration of the trabecular net- work, and to what extent the structural changes differ from those induced by antiresorptive treatment. In the new cycle of the project for which support is sought, we propose to significantly enhance our previously de- veloped MRI-based virtual bone biopsy technology to quantify the structural and mechanical consequences of two fundamentally different forms of drug treatment in patients with metabolic bone disease.
We aim to apply this methodology to patients who are at high risk of fracture and who are treated either with recombinant 1-34 parathyroid hormone or alendronate. We advance the hypothesis that in vivo micro-MRI will be able to distin- guish the structural and mechanical manifestations of short-term treatment and that the method will provide new insight into the structural manifestations of trabecular bone exposed to antiresorptive and anabolic ther- apy. The project will consist of five specific aims involving the development, integration and evaluation of new methods involving data acquisition and reconstruction, motion correction, image processing and analy- sis, as well as image-based computational biomechanics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR041443-13
Application #
7390649
Study Section
Special Emphasis Panel (ZRG1-SBIB-A (90))
Program Officer
Lester, Gayle E
Project Start
1993-01-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
13
Fiscal Year
2008
Total Cost
$427,708
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Chen, Cheng; Jin, Dakai; Liu, Yinxiao et al. (2016) Trabecular bone characterization on the continuum of plates and rods using in vivo MR imaging and volumetric topological analysis. Phys Med Biol 61:N478-N496
Wald, Michael J; Magland, Jeremy F; Rajapakse, Chamith S et al. (2012) Predicting trabecular bone elastic properties from measures of bone volume fraction and fabric on the basis of micromagnetic resonance images. Magn Reson Med 68:463-73
Bhagat, Yusuf A; Rajapakse, Chamith S; Magland, Jeremy F et al. (2011) On the significance of motion degradation in high-resolution 3D ?MRI of trabecular bone. Acad Radiol 18:1205-16
Wright, Alexander C; Lemdiasov, Rostislav; Connick, Thomas J et al. (2011) Helmholtz-pair transmit coil with integrated receive array for high-resolution MRI of trabecular bone in the distal tibia at 7T. J Magn Reson 210:113-22
Sundberg, John P; McElwee, Kevin J; Carroll, Joseph M et al. (2011) Hypothesis testing: CTLA4 co-stimulatory pathways critical in the pathogenesis of human and mouse alopecia areata. J Invest Dermatol 131:2323-4
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
Magland, Jeremy F; Rajapakse, Chamith S; Wright, Alexander C et al. (2010) 3D fast spin echo with out-of-slab cancellation: a technique for high-resolution structural imaging of trabecular bone at 7 Tesla. Magn Reson Med 63:719-27
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
Rajapakse, Chamith S; Magland, Jeremy F; Wald, Michael J et al. (2010) Computational biomechanics of the distal tibia from high-resolution MR and micro-CT images. Bone 47:556-63
Magland, Jeremy F; Jones, Catherine E; Leonard, Mary B et al. (2009) Retrospective 3D registration of trabecular bone MR images for longitudinal studies. J Magn Reson Imaging 29:118-26

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