Preliminary work in this laboratory has demonstrated that extremely low magnitude (<30 Microstrain) mechanical signals can be osteogenic if applied at a high frequency (5 to 50 Hz). Such high frequency low magnitude strains comprise an important constituent of a bone's strain history, suggesting that these mechanical events could represent a significant determinant of bone morphology. We hypothesize that small increases in high frequency loading, introduced non-invasively into the skeleton via vibration, will stimulate an increase in bone mass without sacrificing bone quality. Considering these strain levels are well below (<1/100th) those which may cause damage to the tissue, we believe these signals hold great potential as a mechanical prophylaxis for osteopenia. Using skeletally mature sheep, a randomized, partial 5x4x3 factorial experimental design, evaluating frequency (7.5, 15, 30, 60 or 120 Hz), duration (5, 10, 20 or 40 min), and intensity (0.1, 0.2 or 0.4g) will be used to determine the efficacy of a non-invasive mechanical device to augment the trabeculae of the tibia and femur. A series of in vivo and ex vivo protocols will be used to quantify the ability of this twelve month mechanical intervention to affect both bone mass and morphology. Dual energy x-ray absorptiometry will determine changes in density as a function of time, dynamic and static histomorphometry will quantify the site-specificity, quality, and extent of the response, and mechanical testing will be used to determine if this treatment influences strength and stiffness of the treated regions of the skeleton. Finally, the most osteogenic mechanical signals will be used to determine if bone density, strength, and stiffness can be recovered in the osteopenic skeleton. These experiments may yield new insights into the mechanisms by which mechanical factors control bone morphology, as well as lead to a novel treatment for osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043498-03
Application #
2837553
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Sharrock, William J
Project Start
1996-12-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Orthopedics
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
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Wright, Laura E; Ottewell, Penelope D; Rucci, Nadia et al. (2016) Murine models of breast cancer bone metastasis. Bonekey Rep 5:804
Styner, Maya; Pagnotti, Gabriel M; Galior, Kornelia et al. (2015) Exercise Regulation of Marrow Fat in the Setting of PPAR? Agonist Treatment in Female C57BL/6 Mice. Endocrinology 156:2753-61
Wallace, Ian J; Pagnotti, Gabriel M; Rubin-Sigler, Jasper et al. (2015) Focal enhancement of the skeleton to exercise correlates with responsivity of bone marrow mesenchymal stem cells rather than peak external forces. J Exp Biol 218:3002-9
Frechette, Danielle M; Krishnamoorthy, Divya; Adler, Benjamin J et al. (2015) Diminished satellite cells and elevated adipogenic gene expression in muscle as caused by ovariectomy are averted by low-magnitude mechanical signals. J Appl Physiol (1985) 119:27-36

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