10.07.2015 Views

C - Michigan Technological University

C - Michigan Technological University

C - Michigan Technological University

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decrease in bone trabecular thickness in this model is due to an unbalanced increase inosteoclast and osteoblast activity, leading to net bone resorption [81]. The metacarpus IIIof horses lose 10% of BMD after 140 days of forelimb immobilization; this loss isaccompanied by an increase in the serum resorption marker crosslinked carboxyterminaltelopeptide of type I collagen (CTX) with no change in the bone formation marker bonespecific alkaline phosphatase (BSALP), suggesting that the loss in BMD is due to anincrease in bone resorption with no change in the formation rate [82]. Cats and dogs arealso vulnerable to disuse osteoporosis [14, 83-85]. The immobilized humeri of dogs havesignificantly reduced BMD as well as a 71-98% decrease in cortical strength and a28-74% decrease in trabecular strength than the contra-lateral humeri after 16 weeks ofleft forelimb immobilization [14]. There is also a wealth of studies which quantify boneloss in more common laboratory animals such as non-human primates [86-89], rats[90-98], and mice [48, 99-102]. It is very well established that most animals lose bonewhen subjected to periods of reduced mobility, so it is exciting to study an animal like thehibernating bear, which can undergo months of disuse without losing bone.1.7 Hibernation as a model of disuseHibernation is a state of greatly reduced physical activity and bouts of reducedmetabolism which conserves energy through seasonal periods of reduced foodavailability. The physical activity of bears rapidly declines in the weeks immediatelypreceding hibernation, and bears remain mostly inactive throughout their denning period[13]; thus, hibernation should be an adequate model of disuse (for review see [103]).However, bears maintain BMD and mechanical strength despite these extended periodsof disuse. Mechanical analysis of bones taken before and after hibernation [21],seasonal serum markers of bone metabolism [34, 35], and seasonal histological indicesof cortical and trabecular remodeling [18, 20] together suggest that the rate of boneformation equals the rate of resorption during hibernation in the bear. Thus, there is nonet change in size (e.g. length, thickness), BMD, nor mechanical strength of bone. Incontrast, most existing studies in smaller hibernators suggest that at least some of theseanimals lose bone during winter sleep [104-109]. However, these early studies in smallhibernators are qualitative, and recent quantitative data suggest bone loss may be atleast partially suppressed in hibernating golden-mantled and thirteen-lined ground9

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