We plan to study the factors promoting progressive cartilage destruction in animal models of osteoarthrosis in order to understand the pathophysiology of this condition. The effectiveness of these models has been established by previous experimentation. The joint tissues are studied biochemically, metabolically, and biomechanically. Since the pathology of osteoarthrosis involves destruction of the articular cartilage and the remodeling of the bone adjacent to the joints, we must use in vivo preparations because osteoarthrosis mainly affects mature, older individuals and its development involves an inter-relationship between a variety of tissues, organ cultures utilizing fetal materials are inappropriate. This study, involving collaborative biochemical, biomechanical, anatomical, pathological, and clinical analyses of these models, should provide a better understanding of osteoarthrosis with the hope that the process can some day be halted and reversed. We propose utilizing poorly-protected-against repetitive impulsive loading of a physiologically reasonable amount to create osteoarthrosis in the right knees of rabbits. The left knee is used as a control. We want to establish the threshold levels at which articular cartilage is mechanically injured, the nature of the load which is most deleterious, and the mechanical factors responsible for progression of the joint deterioration. We will first predict the most deleterious force analytically by finite element analysis and test that hypothesis experimentally. We will also utilize stiffening, caused by remodeling of a local area of subchondral bone overlying an implanted plug just under the knee joint of a sheep to study the relationship of bone stiffening and progressive cartilage deterioration. Finite element analysis reveals that such remodeling achieved does increase the stress in the deep layers of the overlying cartilage. We plan to study this in long- and short-term animals to delineate the progression of changes. Experimental results coupled with an expansion of analytical understanding should help define the important mechanical parameters causing joint deterioration in osteoarthrosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM027127-05A1
Application #
3151717
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1979-09-30
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
West Virginia University
Department
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Walker, E R; Boyd, R D; Wu, D D et al. (1991) Morphologic and morphometric changes in synovial membrane associated with mechanically induced osteoarthrosis. Arthritis Rheum 34:515-24
Radin, E L; Burr, D B; Caterson, B et al. (1991) Mechanical determinants of osteoarthrosis. Semin Arthritis Rheum 21:12-21
Wu, D D; Burr, D B; Boyd, R D et al. (1990) Bone and cartilage changes following experimental varus or valgus tibial angulation. J Orthop Res 8:572-85
Lukoschek, M; Burr, D B; Walker, E R et al. (1990) [Synovial membrane and cartilage changes in an arthrosis model. Instability and impact stress model] Z Orthop Ihre Grenzgeb 128:437-41
Schaffler, M B; Radin, E L; Burr, D B (1990) Long-term fatigue behavior of compact bone at low strain magnitude and rate. Bone 11:321-6
Wu, D D; Boyd, R D; Fix, T J et al. (1990) Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits. Calcif Tissue Int 47:18-23
Schaffler, M B; Radin, E L; Burr, D B (1989) Mechanical and morphological effects of strain rate on fatigue of compact bone. Bone 10:207-14
Burr, D B; Schaffler, M B; Yang, K H et al. (1989) Skeletal change in response to altered strain environments: is woven bone a response to elevated strain? Bone 10:223-33
Burr, D B; Schaffler, M B; Yang, K H et al. (1989) The effects of altered strain environments on bone tissue kinetics. Bone 10:215-21
Burr, D B; Schaffler, M B; Frederickson, R G (1988) Composition of the cement line and its possible mechanical role as a local interface in human compact bone. J Biomech 21:939-45

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