Sex differences in sympathetic neural and limb vascular reactivity to mental stress in humans.

Mental stress elicits a robust and consistent forearm vasodilation, but vascular reactivity in the calf remains inconsistent. It has been reported that calf vascular responses to MS may be sex dependent. Muscle sympathetic nerve activity (MSNA) is an important contributor to calf blood flow (CBF), yet the relations between sex, limb blood flow, and MSNA reactivity to mental stress have not been explored. We hypothesized that mental stress would elicit more dramatic vasodilation of the limbs in women and that this might be explained by reduced MSNA reactivity and/or blunted sympathetic vascular transduction. We measured heart rate (HR), mean arterial pressure (MAP), CBF, calf vascular conductance (CVC), forearm blood flow (FBF), forearm vascular conductance (FVC), and MSNA concurrently in 18 men (age: 23 ± 2 yr) and 16 women (age: 24 ± 2 yr) during 5 min of supine baseline and 5 min of mental stress. Mental stress elicited similar increases in MAP (Δ10 ± 1 vs. Δ11 ± 1 mmHg), HR (Δ16 ± 2 vs. Δ17 ± 2 beats/min), FBF (Δ81 ± 16% vs. Δ83 ± 15%), and FVC (Δ62 ± 13% vs. Δ65 ± 13%) in men and women, respectively. In contrast, CBF (Δ16 ± 8% vs. Δ37 ± 9%, P = 0.036) and CVC (Δ4 ± 7% vs. Δ24 ± 8%, P = 0.036) responses were exaggerated in women compared with men. Changes in FVC were significantly correlated with changes in CVC in women (r = 0.681, P = 0.004) but not in men. MSNA reactivity to mental stress was not different between men and women; however, changes in CVC were negatively correlated with increases of MSNA in men (r = -0.411, P = 0.045) but not in women. In conclusion, our data suggest different patterns of calf vascular reactivity to mental stress in men and women that might relate, in part, to altered vascular transduction of MSNA.

Ecology of arthritis.

Osteoarthritis (OA) is a widespread degenerative disease of skeletal joints and is often associated with senescence in vertebrates. OA commonly results from excessive or abnormal mechanical loading of weight-bearing joints ('wear-and-tear'), arising from heavy long-term use or specific injuries; yet, in the absence of injury, the aetiology of OA remains obscure. We show that poor nutritional conditions experienced by moose (Alces alces) early in life are linked to greater prevalence of OA during senescence as well as reduced life expectancy. Moreover, we also found a negative relationship between kill rate by wolves (Canis lupus) and prevalence of OA, suggesting a potential connection between senescence of prey and the population ecology of predator-prey systems. This association between OA and early malnutrition also provides a basis for explaining the observation in anthropology that OA became more prevalent in native Americans as their diet become poorer - the result of relying more on corn and agriculture and less on hunting and gathering.

Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation.

Prolonged disuse (e.g., physical inactivity) typically results in increased bone porosity, decreased mineral density, and decreased bone strength, leading to increased fracture risk in many mammals. However, bears, marmots, and two species of ground squirrels have been shown to preserve macrostructural bone properties and bone strength during long seasons of hibernation while they remain mostly inactive. Some small hibernators (e.g., 13-lined ground squirrels) show microstructural bone loss (i.e., osteocytic osteolysis) during hibernation, which is not seen in larger hibernators (e.g., bears and marmots). Arctic ground squirrels (Urocitellus parryii) are intermediate in size between 13-lined ground squirrels and marmots and are perhaps the most extreme rodent hibernator, hibernating for up to 8 mo annually with body temperatures below freezing. The goal of this study was to quantify the effects of hibernation and inactivity on cortical and trabecular bone properties in arctic ground squirrels. Cortical bone geometrical properties (i.e., thickness, cross-sectional area, and moment of inertia) at the midshaft of the femur were not different in animals sampled over the hibernation and active seasons. Femoral ultimate stress tended to be lower in hibernators than in summer animals, but toughness was not affected by hibernation. The area of osteocyte lacunae was not different between active and hibernating animals. There was an increase in osteocytic lacunar porosity in the hibernation group due to increased lacunar density. Trabecular bone volume fraction in the proximal tibia was unexpectedly greater in the hibernation group than in the active group. This study shows that, similar to other hibernators, arctic ground squirrels are able to preserve many bone properties during hibernation despite being physically inactive for up to 8 mo.

The tensile strength of black bear (Ursus americanus) cortical bone is not compromised with aging despite annual periods of hibernation.

Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they may be able to maintain bone formation. Previously, we found that cortical bone bending strength was not compromised with age in black bears' tibias, despite annual periods of disuse. Here we showed that cortical bone tensile strength (166-198MPa) also does not decrease with age (2-14 years) in black bear tibias. There were also no significant age-related changes in cortical bone porosity in black bear tibias. It is likely that the ability of black bears to maintain bone formation during hibernation keeps bone porosity low (2.3-8.6%) with aging, notwithstanding annual periods of disuse. This low porosity likely preserves ultimate stress with aging. Female bears give birth and nurse during hibernation; however, we found no significant differences between male and female tensile material properties, mineral content, or porosity. Our findings support the idea that black bears, which hibernate 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength.

Black bears with longer disuse (hibernation) periods have lower femoral osteon population density and greater mineralization and intracortical porosity.

Intracortical bone remodeling is persistent throughout life, leading to age related increases in osteon population density (OPD). Intracortical porosity also increases with age in many mammals including humans, contributing to bone fragility and fracture risk. Unbalanced bone resorption and formation during disuse (e.g., physical inactivity) also increases intracortical porosity. In contrast, hibernating bears are a naturally occurring model for the prevention of both age-related and disuse osteoporoses. Intracortical bone remodeling is decreased during hibernation, but resorption and formation remain balanced. Black bears spend 0.25-7 months in hibernation annually depending on climate and food availability. We found longer hibernating bears demonstrate lower OPD and higher cortical bone mineralization than bears with shorter hibernation durations, but we surprisingly found longer hibernating bears had higher intracortical porosity. However, bears from three different latitudes showed age-related decreases in intracortical porosity, indicating that regardless of hibernation duration, black bears do not show the disuse- or age-related increases in intracortical porosity which is typical of other animals. This ability to prevent increases in intracortical porosity likely contributes to their ability to maintain bone strength during prolonged periods of physical inactivity and throughout life. Improving our understanding of the unique bone metabolism in hibernating bears will potentially increase our ability to develop treatments for age- and disuse-related osteoporoses in humans.

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.

Disuse typically uncouples bone formation from resorption, leading to bone loss which compromises bone mechanical properties and increases the risk of bone fracture. Previous studies suggest that bears can prevent bone loss during long periods of disuse (hibernation), but small sample sizes have limited the conclusions that can be drawn regarding the effects of hibernation on bone structure and strength in bears. Here we quantified the effects of hibernation on structural, mineral, and mechanical properties of black bear (Ursus americanus) cortical bone by studying femurs from large groups of male and female bears (with wide age ranges) killed during pre-hibernation (fall) and post-hibernation (spring) periods. Bone properties that are affected by body mass (e.g. bone geometrical properties) tended to be larger in male compared to female bears. There were no differences (p>0.226) in bone structure, mineral content, or mechanical properties between fall and spring bears. Bone geometrical properties differed by less than 5% and bone mechanical properties differed by less than 10% between fall and spring bears. Porosity (fall: 5.5+/-2.2%; spring: 4.8+/-1.6%) and ash fraction (fall: 0.694+/-0.011; spring: 0.696+/-0.010) also showed no change (p>0.304) between seasons. Statistical power was high (>72%) for these analyses. Furthermore, bone geometrical properties and ash fraction (a measure of mineral content) increased with age and porosity decreased with age. These results support the idea that bears possess a biological mechanism to prevent disuse and age-related osteoporoses.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.