Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility and increased fracture risk. The major factor contributing to the structural deterioration of cortical bone is increased porosity caused by bone remodeling. Consequently, the strength and stiffness of bones are reduced. For prolonged bed rest, immobilization and space flight, disuse atrophy of bone is prevalent and increases fracture risk when normal bone loading is resumed. Disuse osteopenia occurs in many animals including rats, roosters, hibernating ground squirrels, sheep, dogs, monkeys and humans. On the contrary, black bears may not develop osteopenia during long periods of disuse (i.e., hibernation) to the extent that other animals do. During hibernation, osteoclastic resorption increases as it does in other animals. However, osteoblastic formation levels remain normal, a metabolic bone feature unique to bears. Additionally, black bears may have a mechanism for more rapid and complete bone recovery from disuse than other animals do. Therefore, we hypothesize that black bears minimize the degradation of bone material properties, which result from annual periods of disuse, because they maintain normal bone formation during disuse and make a rapid and complete recovery of bone mass during remobilization. The overall objective of this project is to understand the effects of annual periods of disuse on bone mechanical properties, histologic features, and mineral composition, and the biological mechanisms that may be involved in bone recovery during remobilization. The goals of the proposed project are (1) to quantify age-related changes in black bear bone mechanical properties, mineral content, and histologic features, and (2) to quantify the effects of black bear serum on mechanically stimulated intracellular calcium signaling in osteoblastic cells in vitro. This will be done with bone tissue from hunter-killed bears, and serum collected from live bears, which will be used for in vitro experiments with osteoblastic cells. The long-term impact of the proposed research includes an understanding of the biological mechanisms involved in disuse osteoporosis and advances in the treatment and prevention of osteoporosis, including the development of novel pharmaceutical therapies. Additionally, this research program is designed to train undergraduate students in the basic skills of experimental design, experimental methods, and data analysis for biological research. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AR050420-01
Application #
6702145
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Sharrock, William J
Project Start
2004-03-12
Project End
2006-02-28
Budget Start
2004-03-12
Budget End
2005-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$72,950
Indirect Cost
Name
Michigan Technological University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
065453268
City
Houghton
State
MI
Country
United States
Zip Code
49931
Wojda, Samantha J; Gridley, Richard A; McGee-Lawrence, Meghan E et al. (2016) Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation. Physiol Biochem Zool 89:72-80
McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren et al. (2015) Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation. J Exp Biol 218:2067-74
Doherty, Alison H; Florant, Gregory L; Donahue, Seth W (2014) Endocrine regulation of bone and energy metabolism in hibernating mammals. Integr Comp Biol 54:463-83
Skedros, John G; Knight, Alex N; Clark, Gunnar C et al. (2013) Scaling of Haversian canal surface area to secondary osteon bone volume in ribs and limb bones. Am J Phys Anthropol 151:230-44
Wojda, Samantha J; Weyland, David R; Gray, Sarah K et al. (2013) Black bears with longer disuse (hibernation) periods have lower femoral osteon population density and greater mineralization and intracortical porosity. Anat Rec (Hoboken) 296:1148-53
Wojda, Samantha J; McGee-Lawrence, Meghan E; Gridley, Richard A et al. (2012) Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation. Bone 50:182-8
McGee-Lawrence, Meghan E; Stoll, Danielle M; Mantila, Emily R et al. (2011) Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength. J Exp Biol 214:1240-7
McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N et al. (2009) Six months of disuse during hibernation does not increase intracortical porosity or decrease cortical bone geometry, strength, or mineralization in black bear (Ursus americanus) femurs. J Biomech 42:1378-83
McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N et al. (2009) Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation). Bone 45:1186-91
McGee, Meghan E; Maki, Aaron J; Johnson, Steven E et al. (2008) Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis). Bone 42:396-404

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