C - Michigan Technological University

1.3 Bone turnover is unbalanced during disuseLike muscle, bone hails from a “use-it-or-lose-it” philosophy. Bone which is beingmechanically loaded by normal daily activities undergoes basal levels of remodeling—mostly for mineral homeostasis and repair of normal fatigue microcracks. However, if thebone is unloaded by immobilization or low gravity, the mechanosensory osteocytessense that the bone is no longer necessary and they signal the other cell types to beginactivation of resorption [22, 25]. An uncoupling of resorption to formation is the result.Bone is broken down more rapidly than it is formed, leading to a net loss. Thisuncoupling can be observed in serum resorption and formation markers in astronauts,and in victims of stroke and spinal cord injury [31-33]. In contrast, serum resorption andformation markers show that osteoclast and osteoblast activities remain balanced duringhibernation in black bears [34]. Furthermore, histological data demonstrates balancedbone remodeling in black bears and in grizzly bears (Ursus arctos horribilis) [18, 20, 21,35]. Thus, bears may conserve bone integrity during hibernation by maintainingbalanced bone resorption and formation. This balance in remodeling is likely drivenby the bear’s need to preserve homeostatic serum calcium. In most cases of disuse,calcium mobilized by the breakdown of bone is excreted in the urine [36]. Bears do notconsume calcium, and do not excrete wastes during hibernation; however, serumcalcium levels remain constant throughout the year, suggesting that any calciumreleased by bone resorption must be returned to mineralized bone by balancedformation [35].1.4 Osteoblast and osteocyte apoptosis results in bone lossCurrent theories suggest that the decoupling of resorption to formation duringdisuse may be due to increased osteoblast and osteocyte apoptosis [37]. According tothe Canalicular Fluid Flow hypothesis, bone can be thought of as a sponge filled withextracellular fluid. The pores of the sponge are formed by the canals and lacunaehousing osteocytes and their processes. When a bone is loaded (i.e. taking a step), thefluid is pushed out of the bone by a slight deformation. Upon unloading (picking the footback up again) the fluid returns to the pores. This cyclic loading and unloading applies a3