Advances in the palliative treatment of patients with established metastatic malignancies have not only prolonged patient survival but also increased the incidence of bony metastases and subsequent pathological fractures. Thus, the prevention and effective treatment of fractures associated with metastatic defects in bone has become an increasingly important aspect of the care of cancer patients. Unfortunately, there are currently available only the crudest of clinical guidelines which may be used to assess the increased fracture risk associated with metastatic lesions in bond. Therefore, the appropriate time for prophylactic stabilization of impending fractures is not known. This investigation will be directed in the long term to the development of comprehensive biomechanical guidelines for the orthopaedic assessment and treatment of metastatic defects in long bones, the proximal femur, and the spine. A four-phase, staged approach will be used. In Task I we will conduct retrospective radiographic reviews of patients exhibiting metastatic lesions in those regions and determine the most frequent sites and approximate shapes of the lesions. As part of this task, we will also develop improved diagnostic imaging procedures for the description of lesion geometries. In Task II, we will determine in-vitro the strength reductions associated with simulated defects in long bones, the proximal femur and the spine. In Task III we will use finite element modeling of defects in these regions to provide a theoretical framework for interpreting the experimental results and assessing the sensitivity of the fracture risk predictors to individual patient variations. In Task IV we will combine these findings by developing structural predictors of fracture risk for individual patients with particular lesions. Biomechanical guidelines appropriate for each skeletal region will be developed and tested retrospectively in clinical populations. These guidelines should represent a significant improvement in the orthopaedic care of patients with metastatic defects in bone.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040211-03
Application #
3179866
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Leong, Natalie L; Anderson, Megan E; Gebhardt, Mark C et al. (2010) Computed tomography-based structural analysis for predicting fracture risk in children with benign skeletal neoplasms: comparison of specificity with that of plain radiographs. J Bone Joint Surg Am 92:1827-33
Snyder, Brian D; Hauser-Kara, Diana A; Hipp, John A et al. (2006) Predicting fracture through benign skeletal lesions with quantitative computed tomography. J Bone Joint Surg Am 88:55-70
Hong, James; Cabe, Greg D; Tedrow, John R et al. (2004) Failure of trabecular bone with simulated lytic defects can be predicted non-invasively by structural analysis. J Orthop Res 22:479-86
Hong, J; Hipp, J A; Mulkern, R V et al. (2000) Magnetic resonance imaging measurements of bone density and cross-sectional geometry. Calcif Tissue Int 66:74-8
Windhagen, H; Hipp, J A; Hayes, W C (2000) Postfracture instability of vertebrae with simulated defects can be predicted from computed tomography data. Spine (Phila Pa 1976) 25:1775-81
Whealan, K M; Kwak, S D; Tedrow, J R et al. (2000) Noninvasive imaging predicts failure load of the spine with simulated osteolytic defects. J Bone Joint Surg Am 82:1240-51
Michaeli, D A; Inoue, K; Hayes, W C et al. (1999) Density predicts the activity-dependent failure load of proximal femora with defects. Skeletal Radiol 28:90-5
Windhagen, H J; Hipp, J A; Silva, M J et al. (1997) Predicting failure of thoracic vertebrae with simulated and actual metastatic defects. Clin Orthop Relat Res :313-9
Hipp, J A; Jansujwicz, A; Simmons, C A et al. (1996) Trabecular bone morphology from micro-magnetic resonance imaging. J Bone Miner Res 11:286-97
Cheal, E J; Hipp, J A; Hayes, W C (1993) Evaluation of finite element analysis for prediction of the strength reduction due to metastatic lesions in the femoral neck. J Biomech 26:251-64

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