Hip fracture is a devastating event. Within a year of the injury, 20-30% of patients die and 50% lose the ability to walk; in the United States these fractures account for 70% ($12 billion) of the direct annual costs of fracture care. Ironically, more than half of the women who sustain a hip fracture would not have qualified for osteoporosis treatment by the current criteria, which are based on bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DXA). Thus, a better approach is needed to determine if an individual is at risk for hip fracture from a fall. Biomechanically, a hip will fracture if the impact force resulting from a fall is greater than the bone strength. Therefore, th ability to determine hip strength is critical for fracture risk assessment. The current best non-invasive tool for direct hip strength assessment is based on quantitative computed tomography (QCT) guided finite element models. However, due to ionizing-radiation dose restrictions, the spatial resolution of clinical QCT (0.6-1 mm) is not sufficient to resolve bone microstructure at the hip. Leveraging our recent work, we propose to develop a novel method for assessing hip strength in vivo using magnetic resonance imaging (MRI) coupled with biomechanics. First, we propose to optimize our current MRI protocol for microstructural hip imaging to achieve 0.23-0.5 mm spatial resolution, and to reduce the finite element computation time to less than 30 minutes for predicting hip strength simulating a fall onto the hip on a desktop computer. Second, we propose to validate the accuracy of our MRI-derived hip strength technique by comparing the values obtained by this technique to the values obtained from the gold standard technique of mechanical testing of cadaveric femurs obtained from 30 donors. Third, we propose to apply the method optimized and validated above to determine if patients with hip fracture (N=40) have low bone strength for a fall onto the hip compared to matched healthy controls (N=40). We also propose to determine the test-retest reproducibility of MRI-derived strength by repeating the scanning and analysis in 10 healthy subjects. If further validated in longitudinal studies, the groundwork proposed under this project has the potential to introduce a paradigm shift for assessing hip fracture risk and monitoring the efficacy of osteoporosis treatment.

Public Health Relevance

Hip fractures are devastating, accounting for 20-30% mortality and substantial disability that together cost $12 billion in fracture care annually. Bone density testing has many limitations, including failure to identify more than half of the individuals who wll have a hip fracture. We propose a method to directly estimate hip strength that could potentially guide physicians to initiate and monitor treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR068382-04
Application #
9530552
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Nicks, Kristy
Project Start
2015-08-01
Project End
2020-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
4
Fiscal Year
2018
Total Cost
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
Rajapakse, Chamith S; Chang, Gregory (2018) Micro-Finite Element Analysis of the Proximal Femur on the Basis of High-Resolution Magnetic Resonance Images. Curr Osteoporos Rep 16:657-664
Rajapakse, Chamith S; Kobe, Elizabeth A; Batzdorf, Alexandra S et al. (2018) Accuracy of MRI-based finite element assessment of distal tibia compared to mechanical testing. Bone 108:71-78
Chang, Gregory; Rajapakse, Chamith S; Chen, Cheng et al. (2018) 3-T MR Imaging of Proximal Femur Microarchitecture in Subjects with and without Fragility Fracture and Nonosteoporotic Proximal Femur Bone Mineral Density. Radiology 287:608-619
Rajapakse, Chamith S; Lindborg, Carter; Wang, Haitao et al. (2017) Analog Method for Radiographic Assessment of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva. Acad Radiol 24:321-327
Chang, Gregory; Boone, Sean; Martel, Dimitri et al. (2017) MRI assessment of bone structure and microarchitecture. J Magn Reson Imaging 46:323-337
Rajapakse, Chamith S; Hotca, Alexandra; Newman, Benjamin T et al. (2017) Patient-specific Hip Fracture Strength Assessment with Microstructural MR Imaging-based Finite Element Modeling. Radiology 283:854-861
Rajapakse, Chamith S; Leonard, Mary B; Kobe, Elizabeth A et al. (2017) The Efficacy of Low-intensity Vibration to Improve Bone Health in Patients with End-stage Renal Disease Is Highly Dependent on Compliance and Muscle Response. Acad Radiol 24:1332-1342