Browsing by Subject "bone loss"
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Item A mechanistic examination of the metabolic regulation of insulin resistance, sarcopenia, and osteoporosis(2007-11-14) Edgar Lichar Dillon; Melinda Sheffield-Moore, Ph.D.; Randall J. Urban, M.D.; Kevin R. Short, Ph.D.; Concepcion Diaz-Arrastia, M.D.; Blake B. Rasmussen, Ph.D.Aging is associated with a number of physiological changes, including increased risk of insulin resistance and type 2 diabetes mellitus (T2DM), decreased muscle mass and strength, and decreased bone mass and bone mineral density (BMD). The aim of the studies presented were to investigate 1) the kinetics of glucose-derived breath CO2 between drug naïve impaired glucose tolerant (IGT) and normal glucose tolerant (NGT) individuals following an oral glucose load, 2) the effects of chronic oral supplementation of essential amino acids (EAA) on the acute muscle protein synthetic response to an oral bolus of EAA in older men and women, and 3) the effects of continuous and monthly cycled administration of testosterone on markers of bone metabolism in older men with low normal endogenous testosterone production.\r\nStudy 1) During a 10-h oral glucose tolerance test, blood and breath samples were collected following ingestion of 75 g of glucose isotopically labeled with 150 mg of U-13C6-Glucose. Glucose-derived breath 13CO2 was lower in IGT as compared to NGT from 1 to 3.5 h post-glucose (P≤0.05). Glucose-derived breath CO2 kinetics measured during the immediate post-glucose ingestion period may assist in recognition of undiagnosed IGT in at-risk individuals during the pre-diabetes stage of T2DM.\r\nStudy 2) Older men and women received daily between-meal supplements of either 7.5 g EAA (LO), 15 g EAA (HI), or placebo (PL) for three months. Chronic EAA supplementation increased net phenylalanine uptake in the leg of LO and HI (P<0.05) without altering the magnitude of the acute FSR or total and phosphorylated Akt, mTOR, S6K1 or 4E-BP1 response. The magnitude of the anabolic response to an oral EAA ingestion in healthy older men and women remains intact after 3 months of EAA supplementation.\r\nStudy 3) Older men received continuous weekly testosterone injections for 5 months (TE), monthly cycled testosterone treatment (MO) or weekly placebo (PL). Continuous weekly testosterone administration resulted in decreased serum n-telopeptide (NTX) and serum osteocalcin (OC) in TE. Continuous testosterone treatment results in a decrease in both bone resorption and bone formation in older men.Item Skeletal Response to Simulated Microgravity Exposures and Exercise in the Adult Rat Model(2013-04-29) Shirazi-Fard, YasamanMechanical unloading has deleterious effects on the musculoskeletal system and results in significant reductions in bone density, mass, and strength, which do not fully recover even years after returning to weightbearing. For example, the rate of bone loss in microgravity is 10-fold more rapid than the rate of loss seen in elderly Caucasian females, the population group most predisposed to osteoporosis. This raises concern with individuals who are exposed to multiple bed rest periods or crewmembers who make repeated missions. Exercise offers a way to reduce or reverse these effects. Dual-energy X-ray absorptiometry (DXA) densitometry and bone mineral density (BMD) alone are generally insufficient for capturing the complex changes in bone mass, structure, and integrity and not an accurate predictor of fracture risk. Therefore, it is essential to measure the mechanical properties of bone tissue directly using animal models. The hindlimb unloaded (HU) rat model is a well-established ground-based analog for studying bone response to disuse and effects of spaceflight. The current study is one of the very few that has measured longitudinally densitometric and mechanical properties of bone after repeated simulated microgravity and long-term recovery at multiple anatomic sites in skeletally mature rats. The specific aims were to characterize 1) loss and recovery dynamics of bone following a period of unloading, 2) bone response after a second exposure to 28 days of HU, following an initial 28 days of HU and a recovery period equal to twice the duration of initial exposure, and 3) effects of resistance exercise during recovery period following an initial HU exposure and its effects on a subsequent exposure. In general, our data showed that bone response to unloading and recovery is site-specific. More specifically, we found that: 1) the rat proximal tibia metaphysis modeled the loss and discordant recovery dynamics as seen in the International Space Station (ISS) crewmembers proximal femur better than the rat femoral neck; 2) the initial exposure to HU has minimal effect on the subsequent HU exposure, and detrimental effects of the second HU exposure were milder than the initial due to reduced mechanosensitivity of the bone; 3) exercise significantly enhanced recovery following the initial HU exposure, and losses during the second exposure were not affected by exercise in most cases.Item The Effects of Multiple Unloading Exposures on Bone Properties in the Femur of Adult Male Rats(2012-07-16) Morgan, Derrick ScottNASA goals include long-term International Space Station (ISS) missions and the ambitious objective of eventually sending astronauts to Mars. Unfortunately, exposure to unloading due to microgravity during spaceflight has been shown to cause detrimental health effects on bone. Therefore, NASA is seeking a ground-based animal model to study the long-term effects of unloading on bone in order to better insure the health and mission capability of astronauts. The hindlimb unloaded (HU) rat model was used to study the effects of multiple unloading exposures and aging on bone properties. Six month old, adult, male Sprague-Dawley rats were separated into the following groups: baseline (BL, sacrificed when received at 6 months age), aging cage control (AC, normal weight-bearing cage activity), 1HU7 (unloaded for 1 month starting at 7 months of age and allowed to recover for 3 months), 1HU10 (normal cage activity until 10 months of age, unloaded for 1 month, recovered for 2 months), and 2HU10 (unloaded for 1 month at 7 months of age, allowed to recover for 2 months, unloaded again for 1 month at 10 months of age, followed by 2 months of recovery). Every 28 days a subset of animals (n=15) were euthanized and both femurs were excised. A peripheral quantitative computed tomography (pQCT) scanner was used to collect densitometric and geometric properties at the right and left femoral neck and at the left femoral midshaft. Mechanical testing (axial and lateral compression of the femoral neck and 3pt bending of the midshaft) was performed at each location and strength indices based on pQCT parameters were calculated. Femoral neck properties decreased due to HU but recovered with respect to increase over HU, BL, and AC by the end of the recovery periods. Femoral midshaft properties were relatively unaffected, but did show slight decreases for older animals at month 10, which recovered during the two month recovery period. Femoral neck geometry exhibited increased endocortical resorption and periosteal apposition of the cortical shell which suggests that trabecular bone plays an important role in how the total bone is affected by HU. Densitometric properties were affected less by HU with respect to BL than were mechanical strength values. Results suggest that femoral neck is more affected by unloading than midshaft, particularly for multiple exposures of unloading. Also, aging does not appear to be a critical factor for bone loss due to HU for either femoral neck or midshaft.