Exercise training modifies the bone and endocrine response to graded reductions in energy availability in skeletally mature female rodents.

Introduction: Reductions in energy availability leading to weight loss can induce loss of bone and impact important endocrine regulators of bone integrity. We sought to elucidate whether endurance exercise (EX) can mitigate bone loss observed in sedentary (SED) skeletally mature rodents subjected to graded energy deficits.

Methods: Female virgin rats (n=84, 5-mo-old; 12/group) were randomized to baseline controls and either sedentary (SED) or exercise (EX) conditions, and within each exercise status to adlib-fed (ADLIB), or moderate (MOD) or severe (SEV) energy restriction diets for 12 weeks.

Rapid Transition from a High-Fat, High-Fructose to a Low-Fat, Low-Fructose Diet Reverses Gains in Bone Mass and Strength.

Purpose: Obesity is thought to negatively impact bone quality and strength despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high-fat, high-sugar (HFS) diet would impair bone quality and strength, and 2) a change from an HFS diet to a low-fat, low-sugar (LFS) would reverse HFS-induced impairments to bone quality and strength.

Methods: Six-week-old male C57Bl/6 mice ( n = 10/group) with access to a running wheel were randomized to an LFS diet or an HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 wk.

Oral Estradiol Impact on Mitigating Unloading-Induced Bone Loss in Ovary-Intact Rats.

The impact of the spaceflight environment on endogenous estrogen production in female crewmembers and the resulting impact on other adaptations, like bone loss, is an under-investigated topic. Hence, we investigated the interaction of exogenous 17- estradiol (E2) treatment and disuse to test the hypothesis that E2 treatment would mitigate disuse-induced bone loss. There were 40 virgin female Sprague-Dawley rats (5 mo old) randomized to placebo (PL; 0 ppm E2) or estrogen (E2; 10 ppm E2) treatments, delivered via custom-made rodent diets; half of each group was randomized to either weightbearing (WB) or hindlimb unloading (HU) for 39 d.

DSS-induced colitis produces inflammation-induced bone loss while irisin treatment mitigates the inflammatory state in both gut and bone.

Chronic pediatric inflammatory bowel disease (IBD) leads to lack of bone accrual, bone loss, and increased fractures. Presently there is no cure, and many IBD treatments incur negative side effects. We previously discovered treatment with exogenous irisin resolved inflammatory changes in the colon, gut lymphatics, and bone in a mild IBD rodent model.

Regulation of mitochondrial quality following repeated bouts of hindlimb unloading.

Muscle disuse impairs muscle quality and is associated with increased mortality. Little is known regarding additive effects of multiple bouts of disuse, which is a common occurrence in patients experiencing multiple surgeries. Mitochondrial quality is vital to muscle health and quality; however, to date mitochondrial quality control has not been investigated following multiple bouts of disuse.

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice.

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy Fe or sham ( = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days.

Responses of skeletal muscle size and anabolism are reproducible with multiple periods of unloading/reloading.

Mechanical unloading has long been understood to contribute to rapid and substantial adaptations within skeletal muscle, most notably, muscle atrophy. Studies have often demonstrated that many of the alterations resulting from disuse are reversed with a reintroduction of load and have supported the concept of muscle plasticity. We hypothesized that adaptations during disuse and recovery were a repeatable/reproducible phenomenon, which we tested with repeated changes in mechanical load.

Differential responses of mechanosensitive osteocyte proteins in fore- and hindlimbs of hindlimb-unloaded rats.

Osteocytes are believed to be the primary mechanosensors of bone tissue, signaling to osteoblasts and osteoclasts by releasing specific proteins. Sclerostin, interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I) are osteocyte proteins that signal to osteoblasts. The primary objective of this study was to determine if osteocyte protein response to mechanical unloading is restricted to the unloaded bone using the hindlimb unloading (HU) rodent model.

Moderate intensity resistive exercise improves metaphyseal cancellous bone recovery following an initial disuse period, but does not mitigate decrements during a subsequent disuse period in adult rats.

Spaceflight provides a unique environment for skeletal tissue causing decrements in structural and densitometric properties of bone. Previously, we used the adult hindlimb unloaded (HU) rat model to show that previous exposure to HU had minimal effects on bone structure after a second HU exposure followed by recovery. Furthermore, we found that the decrements during second HU exposure were milder than the initial HU cycle.

Increased resistance during jump exercise does not enhance cortical bone formation.

Purpose: This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses.

Methods: Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk.

Previous exposure to simulated microgravity does not exacerbate bone loss during subsequent exposure in the proximal tibia of adult rats.

Extended periods of inactivity cause severe bone loss and concomitant deterioration of the musculoskeletal system. Considerable research has been aimed at better understanding the mechanisms and consequences of bone loss due to unloading and the associated effects on strength and fracture risk. One factor that has not been studied extensively but is of great interest, particularly for human spaceflight, is how multiple or repeated exposures to unloading and reloading affect the skeleton.

Partial weight bearing does not prevent musculoskeletal losses associated with disuse.

Purpose: The purpose of this study was to investigate whether partial weight-bearing activity, at either one-sixth or one-third of body mass, blunts the deleterious effects of simulated microgravity (0G) after 21 d on muscle mass and quantitative/qualitative measures of bone.

Methods: Using a novel, previously validated partial weight-bearing suspension device, mice were subjected to 16% (G/3, i.e.

The role of acidemia in maternal binge alcohol-induced alterations in fetal bone functional properties.

Background: Heavy alcohol consumption during pregnancy negatively impacts the physical growth of the fetus. Although the deleterious effects of alcohol exposure during late gestation on fetal brain development are well documented, little is known about the effect on fetal bone mechanical properties or the underlying mechanisms. The purpose of this study was to investigate the effects of late gestational chronic binge alcohol consumption and alcohol-induced acidemia, a critical regulator of bone health, on functional properties of the fetal skeletal system.

β-1 adrenergic agonist mitigates unloading-induced bone loss by maintaining formation.

Introduction: Recent data indicate a direct relationship between the sympathetic nervous system and bone metabolism. The purpose of this study was to evaluate the effects of a beta-1 adrenergic (Adrb1) agonist, dobutamine (DOB), on disuse-induced changes in bone integrity during 28 d of hindlimb unloading (HU).

Methods: Male Sprague-Dawley rats, age 6 months, were assigned to either a normal cage activity (CC) or HU (n = 24/group).

Discordant recovery of bone mass and mechanical properties during prolonged recovery from disuse.

Profound bone loss at weight bearing sites is a primary effect of long-duration spaceflight. Moreover, a significant increase in estimated fracture risk remains even 1 year after returning to Earth; hence, it is important to define how quickly bone integrity can recover following prolonged disuse. This study characterized the loss and recovery dynamics of bone following a period of rodent hindlimb unloading in three anatomic sites.

Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment.

The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU + ALEN), SRT (HU + SRT), or a combination of ALEN and SRT (HU + SRT/ALEN) for 28 days. HU + SRT and HU + SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000 ms isometric + 1000 ms eccentric).

Simulated resistance training during hindlimb unloading abolishes disuse bone loss and maintains muscle strength.

This study was designed to determine the effectiveness of simulated resistance training (SRT) without weight bearing in attenuating bone and muscle loss during 28 day hindlimb unloading (HU) in mature male rats. An ambulatory control group (CC) and four groups of HU rats were used: HU, HU + anesthesia (ANHU), HU + eccentric muscle contractions (HU + ECC), and HU + isometric and eccentric muscle contractions (HU + ISO/ECC). Animals in the two SRT groups were trained once every other day at 100% daily peak isometric torque (P(0)).

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat.

Osteopenia and an enhanced risk of fracture often accompany type 1 diabetes. However, the association between type 2 diabetes and bone mass has been ambiguous with reports of enhanced, reduced, or similar bone mineral densities (BMDs) when compared with healthy individuals. Recently, studies have also associated type 2 diabetes with increased fracture risk even in the presence of higher BMDs.

Voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice.

The study's objective was to investigate how estrogen deficiency and run training affect the tibial bone-soleus muscle functional relationship in mice. Female mice were assigned into one of two surgical conditions, ovariectomy (OVX) or sham ovariectomy (sham), and one of two activity conditions, voluntary wheel running (Run) or sedentary (Sed). To determine whether differences observed between OVX and sham conditions could be attributed to estradiol (E(2)), additional OVX mice were supplemented with E(2).

Raloxifene enhances material-level mechanical properties of femoral cortical and trabecular bone.

We have previously documented that raloxifene enhances the mechanical properties of dog vertebrae independent of changes in bone mass, suggesting a positive effect of raloxifene on material-level mechanical properties. The goal of this study was to determine the separate effects of raloxifene on the material-level mechanical properties of trabecular and cortical bone from the femur of beagle dogs. Skeletally mature female beagles (n = 12 per group) were treated daily for 1 yr with oral doses of vehicle or raloxifene (0.

Binge alcohol exposure during all three trimesters alters bone strength and growth in fetal sheep.

Women who drink while pregnant are at a high risk of giving birth to children with neurodevelopmental disorders. Heavy consumption of alcohol during pregnancy is also known to be deleterious to fetal bone growth in both humans and laboratory animals. However, nothing is known regarding the effect of maternal moderate and heavy alcohol binging on fetal and maternal bone strength.

Evaluation of displacement of the digital cushion in response to vertical loading in equine forelimbs.

Objective: To evaluate patterns of digital cushion (DC) displacement that occur in response to vertical loading of the distal portion of the forelimb in horses. Sample Population-Forelimbs from 10 horses with normal feet.

Procedure: Patterns of DC displacement induced by in vitro vertical limb loading were determined.

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats.

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats.