Pathologic vertebral fractures result in pain and disability in a large population of patients with trabacular bone deficiencies. Increasing life expectancy of cancer patients allowing skeletal metastatic and myeloma progression and aging of the general population is expected to lead to a significant increase in the at risk population. We hypothesize that the lack of accurate and reliable clinical predictors of fracture risk in pathologic vertebrae is due to a lack of understanding of the underlying mechanisms. We further hypothesize that the underlying mechanism is the accumulation of a critical level of damage (microcracking) in trabecular bone. Thirdly, we hypothesize that the damage accumulation process is different in diffuse loss of bone versus focal loss of bone, leading to different levels of fracture risk at a given loss of bone mass. Our long term goal is to better understand and thereby better manage the clinical problem of pathologic vertebral fractures. As a first step, we propose to develop a Finite Element Analysis (FEA) model to investigate the damage accumulation process in vertebral trabacular bone. We will develop a model of trabecular bone behavior including damaging effects with material parameters derived from cyclic creep tests of vertebral bone specimens. This material model will be implemented within a FEA model to predict the response of vertebral trabecular bone specimens to leading (tension, compression, torsion). These predictions will be compared with experimental results from mechanical tests of vertebral trabecular specimens. """"""""Pathologic"""""""" conditions will be investigated using FEA models of specimens with """"""""high"""""""" or """"""""low"""""""" densities and cylindrical osteolytic defects under loading. Mechanical testing of specimens with """"""""high"""""""" and """"""""low"""""""" apparent densities and stimulated defects will be used to examine the analytical predictions. These examinations of the effects of damage accumulation on the material behavior of vertebral trabacular bone will provide significant information on trabacular bone behavior. More importantly, it will provide the basis for further investigations towards the overall goal of interpreting non-invasive clinical measures of trabecular bone adequacy to determine long-term likelihood of pathologic vertebral fracture.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR047372-03
Application #
6632786
Study Section
Special Emphasis Panel (ZAR1-AAA-C (O1))
Program Officer
Freeman, Julia B
Project Start
2001-03-15
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$573,898
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gonzalez-GarcĂ­a, Ines; Zhao, Yani; Ju, Songguang et al. (2009) IL-17 signaling-independent central nervous system autoimmunity is negatively regulated by TGF-beta. J Immunol 182:2665-71
Katsumata, Yasuhiro; Ridgway, William M; Oriss, Timothy et al. (2007) Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. J Autoimmun 29:174-86
Deslouches, Berthony; Gonzalez, Ivan A; DeAlmeida, Dilhari et al. (2007) De novo-derived cationic antimicrobial peptide activity in a murine model of Pseudomonas aeruginosa bacteraemia. J Antimicrob Chemother 60:669-72
Navratil, Jeannine S; Manzi, Susan; Kao, Amy H et al. (2006) Platelet C4d is highly specific for systemic lupus erythematosus. Arthritis Rheum 54:670-4
Deslouches, Berthony; Phadke, Shruti M; Lazarevic, Vanja et al. (2005) De novo generation of cationic antimicrobial peptides: influence of length and tryptophan substitution on antimicrobial activity. Antimicrob Agents Chemother 49:316-22
Khan, Mustafa H; Li, Zhaozhu; Wang, James H-C (2005) Repeated exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration. Clin J Sport Med 15:27-33
Deslouches, Berthony; Islam, Kazi; Craigo, Jodi K et al. (2005) Activity of the de novo engineered antimicrobial peptide WLBU2 against Pseudomonas aeruginosa in human serum and whole blood: implications for systemic applications. Antimicrob Agents Chemother 49:3208-16
Phadke, Shruti M; Deslouches, Berthony; Hileman, Sara E et al. (2005) Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection. J Nutr 135:1289-93
Manzi, Susan; Navratil, Jeannine S; Ruffing, Margie J et al. (2004) Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus. Arthritis Rheum 50:3596-604
Li, Zhaozhu; Yang, Guoguang; Khan, Mustafa et al. (2004) Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching. Am J Sports Med 32:435-40

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