Disuse osteoporosis increases fracture risk for patients who have had a stroke or spinal cord injury. Animals also lose bone mass and strength during inactivity because bone formation is uncoupled from resorption. Cortical bone mineral apposition rate is reduced approximately 50% in hind-limb suspended rats compared to controls. During disuse, intracortical porosity increases and bone strength decreases. In humans, bone loss during disuse is associated with increased calcium excretion. In contrast, bears do not eat, drink, urinate, or defecate (i.e., excrete calcium) during hibernation, and blood calcium concentration remains constant throughout the year. There is some evidence to suggest that bone formation remains coupled to bone resorption in hibernating bears. Thus, bone mass and strength losses should be small, if they occur at all, in bears during hibernation (i.e., disuse). In this research proposal, it is hypothesized that bears maintain bone cross-sectional properties and strength during annual periods of disuse because they maintain bone formation. If this is true, it will support the idea that bears have biological mechanisms to prevent disuse osteoporosis. Elucidating the biological mechanisms may help us design therapies to treat human osteoporoses. This may be accomplished by targeting genes and circulating hormones which are differentially expressed in bears and humans during disuse. This grant proposes to measure cortical bone strength, cross-sectional geometric properties (e.g., moments of inertia), and histological indices of bone formation before and after hibernation. Femurs from hunter-killed bears will be collected from voluntary donation by hunters. They will be loaded to failure in bending on a mechanical testing machine to determine the fracture strength and energy of the bones. Microscopically, the degree of porosity and level of bone formation activity will be quantified with image analysis software. The level of mineralization of the bones will be determined by quantifying the weight percentage of calcium-phosphate mineral in the bone tissue. If the bones are not weaker after hibernation than before hibernation, it will support the theory the bears have evolved biological mechanisms to prevent disuse osteoporosis. ? ? ?

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 #
2R15AR050420-03
Application #
7071356
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Sharrock, William J
Project Start
2004-03-12
Project End
2009-03-31
Budget Start
2006-05-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2006
Total Cost
$225,538
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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