Bone Mechanics in Hibernating Bears

描述（由申请人提供）：废用性骨质疏松症增加中风或脊髓损伤患者骨折的风险。动物在不活动时也会失去骨量和强度，因为骨骼的形成与吸收分离。与对照组相比，后肢悬吊大鼠的皮质骨矿物质附着率降低了约50%。在不使用期间，皮质内孔隙度增加，骨强度降低。在人类中，废弃期间的骨质流失与钙排泄增加有关。相比之下，熊在冬眠期间不吃、不喝、不小便、不排便（即排泄钙），血钙浓度全年保持不变。有一些证据表明，冬眠的熊的骨形成仍然与骨吸收有关。因此，如果熊在冬眠（即不使用）期间发生骨量和强度损失，那么它们应该很小。在这项研究计划中，假设熊在每年不使用期间保持骨的横截面特性和强度，因为它们维持骨的形成。如果这是真的，它将支持熊有生物机制来预防老年骨质疏松症的观点。阐明其生物学机制可能有助于我们设计治疗人类骨质疏松症的疗法。这可以通过靶向熊和人类在废弃期间表达差异的基因和循环激素来实现。本项目拟测量冬眠前后皮质骨强度、横截面几何特性（如转动惯量）和骨形成的组织学指标。被猎杀的熊的股骨将由猎人自愿捐赠。它们将在机械试验机上加载到弯曲失效，以确定骨骼的断裂强度和能量。显微镜下，孔隙度和骨形成活动水平将通过图像分析软件进行量化。骨骼的矿化程度将通过量化骨组织中磷酸钙矿物的重量百分比来确定。如果冬眠后的骨骼没有比冬眠前更弱，这将支持熊进化出生物机制来预防废用性骨质疏松症的理论。

DESCRIPTION (provided by applicant): 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.