The goal of this work is to understand how bone adapts to its mechanical environment, and to further the validation and development of predictive computational models for strain-induced cortical bone remodeling. We hypothesize that bone formation on the cortical-endosteal surface can be reactivated when mechanical strains are elevated, causing bone formation within the marrow cavity; and that alterations of the mechanical environment act on the differentiation of cells rather than on individual cell vigor. These hypotheses will be tested both experimentally and analytically. The proposed research uses the ulnar osteotomy dog model we have developed. Eighteen skeletally mature (1-2 year old) beagle dogs will have 1-2 cm segment of the distal ulna removed to overload the intact radius. A separate group of eighteen dogs will have ulnar osteotomies, but the osteotomy gap will be spanned with a 5-hole metal fixation plate. This will test the effect of osteotomy without overload of the radius. A third group (n-18) will have sham operations. Following surgery, fluorochrome markers will be given to monitor bone formation. Force plate data will be collected before and after surgery. Two days prior to sacrifice, bone strains will be measured on the radius using three sets of rosette strain gages. Six animals in each group will be sacrificed at one, six, or 12- months. An additional six dogs per group will be used to measure acute strain changes after either an ulnar osteotomy alone, or after a plated osteotomy. Following sacrifice, undecalcified sections of bone from the radius and ulna will be prepared and histomorphometric measurements will quantify the tissue-level and cell-level adaptation of the bone to a change in strain. These data will then be used to relate Hart's computational model to bone cell activity by using cellular and tissue dynamics to define rules governing bone remodeling.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR040655-02
Application #
3161084
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1992-05-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Coleman, John C; Hart, Richard T; Burr, David B (2003) Reconstructed bone end loads on the canine forelimb during gait. J Biomech 36:1837-44
Coleman, John C; Hart, Richard T; Owan, Ichiro et al. (2002) Characterization of dynamic three-dimensional strain fields in the canine radius. J Biomech 35:1677-83
Owan, I; Burr, D B; Turner, C H et al. (1997) Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. Am J Physiol 273:C810-5