The relationship of bone remodeling processes to repair of microdamage caused by cyclic loading is postulated to be an essential component of the regulatory physiology which maintains the mechanical integrity of compact bone. Inadequacy of the remodeling- microdamage repair process is posited to be the cause of stress fractures. However, despite their significance, the mechanisms of microdamage accumulation in living bones, its repair by remodeling, and the dysfunction of these processes in the development of stress fractures are poorly understood. In the proposed studies, we will test the hypothesis that intracortical remodeling processes serves to preferentially remove and replace fatigue damaged compact bone. The second hypothesis which will be tested is that the increased bone remodeling activity caused by cyclic loading, with its commensurate increase in intracortical porosity, is a key causal feature in the development of stress fractures. Accordingly, the objectives of the proposed studies are to: 1) Examine fatigue processes and the accumulation of microdamage in compact bone with low stress loading. Microdamage will be assessed in standardized specimens of compact bone and in devitalized long bones. 2) Study the function and time course of intracortical remodeling in the repair of microdamage in compact bone, using an in vivo model, 3) Examine the role of remodeling and microdamage the development of stress fractures in an experimental animal model. Short-term pharmacological suppression of bone remodeling will be used to evaluate the role of bone remodeling in the development of stress fractures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR041210-03
Application #
2080556
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1992-09-15
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Orthopedics
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Liu, Zhongbo; Kennedy, Oran D; Cardoso, Luis et al. (2016) DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH. FASEB J 30:635-52
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Cardoso, Luis; Schaffler, Mitchell B (2015) Changes of elastic constants and anisotropy patterns in trabecular bone during disuse-induced bone loss assessed by poroelastic ultrasound. J Biomech Eng 137:
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