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Dietary countermeasures to mitigate detrimental spaceflight-induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single-blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14-day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E and 80 µg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole-body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts.
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Antioxidantes , Densidad Ósea , Humanos , Masculino , Adulto , Antioxidantes/uso terapéutico , Reposo en Cama/efectos adversos , Inclinación de Cabeza , Método Simple Ciego , Suplementos DietéticosRESUMEN
BACKGROUND: Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. OBJECTIVES: We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. METHODS: This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 µg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. RESULTS: The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum ß-C-telopeptide of type I collagen (ß-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest-related changes were observed. CONCLUSIONS: Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.
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Antioxidantes/administración & dosificación , Reposo en Cama , Resorción Ósea , Suplementos Dietéticos , Inclinación de Cabeza , Adulto , Biomarcadores , Remodelación Ósea , Resorción Ósea/prevención & control , Calcio/metabolismo , Colágeno Tipo I , Ácidos Grasos Omega-3/administración & dosificación , Humanos , Masculino , Polifenoles/administración & dosificación , Selenio/administración & dosificación , Método Simple Ciego , Vitamina E/administración & dosificación , Adulto JovenRESUMEN
For the prevention and treatment of bone loss related diseases, focus has been put on naturally derived substances such as polyphenols. Based on human intervention studies, this review gives an overview of the effects of dietary significant polyphenols (flavonoids, hydroxycinnamic acids, and stilbenes) on bone turnover. Literature research was conducted using PubMed database and articles published between 01/01/2008 and 31/12/2018 were included (last entry: 19/02/2019). Randomized controlled trials using oral polyphenol supplementation, either of isolated polyphenols or polyphenols-rich foods with healthy subjects or study populations with bone disorders were enclosed. Twenty articles fulfilled the inclusion criteria and the average study quality (mean Jadad score: 4.5) was above the pre-defined cut-off of 3.0. Evidence from these studies does not allow an explicit conclusion regarding the effects of dietary important polyphenols on bone mineral density and bone turnover markers. Differences in study population, habitual diet, lifestyle factors, applied polyphenols, used doses, and polyphenol bioavailability complicate the comparison of study outcomes.
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Huesos/efectos de los fármacos , Huesos/metabolismo , Polifenoles/farmacología , Suplementos Dietéticos , HumanosRESUMEN
Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.
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Context: The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined. Objective: We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Design and Setting: Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany. Participants and Interventions: Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest. Outcome Measures: Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers. Results: Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations. Conclusions: Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance.
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Tejido Adiposo/metabolismo , Reposo en Cama/efectos adversos , Biomarcadores/metabolismo , Metabolismo Energético/fisiología , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/etiología , Resistencia a la Insulina/fisiología , Adiposidad/fisiología , Adulto , Biomarcadores/sangre , Composición Corporal/fisiología , Estudios Cruzados , Dieta , Diagnóstico Precoz , Intolerancia a la Glucosa/metabolismo , Humanos , Estudios Longitudinales , Masculino , Factores de TiempoRESUMEN
Bed rest (BR) causes bone loss, even in otherwise healthy subjects. Several studies suggest that ambulatory subjects may benefit from high-protein intake to stimulate protein synthesis and to maintain muscle mass. However, increasing protein intake above the recommended daily intake without adequate calcium and potassium intake may increase bone resorption. We hypothesized that a regimen of high-protein intake (HiPROT), applied in an isocaloric manner during BR, with calcium and potassium intake meeting recommended values, would prevent any effect of BR on bone turnover. After a 20-day ambulatory adaptation to a controlled environment, 16 women participated in a 60-day, 6° head-down-tilt (HDT) BR and were assigned randomly to 1 of 2 groups. Control (CON) subjects (n = 8) received 1 g/(kg body mass·day)-1 dietary protein. HiPROT subjects (n = 8) received 1.45 g protein/(kg body mass·day)-1 plus an additional 0.72 g branched-chain amino acids per day during BR. All subjects received an individually tailored diet (before HDTBR: 1888 ± 98 kcal/day; during HDTBR: 1604 ± 125 kcal/day; after HDTBR: 1900 ± 262 kcal/day), with the CON group's diet being higher in fat and carbohydrate intake. High-protein intake exacerbated the BR-induced increase in bone resorption marker C-telopeptide (>30%) (p < 0.001) by the end of BR. Bone formation markers were unaffected by BR and high-protein intake. We conclude that high-protein intake in BR might increase bone loss. Further long-duration studies are mandatory to show how the positive effect of protein on muscle mass can be maintained without the risk of reducing bone mineral density.
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Reposo en Cama , Densidad Ósea/efectos de los fármacos , Resorción Ósea/prevención & control , Proteínas en la Dieta/administración & dosificación , Adulto , Composición Corporal , Dieta , Femenino , Humanos , Simulación del EspacioRESUMEN
The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.
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Reposo en Cama , Densidad Ósea , Proteínas Morfogenéticas Óseas/sangre , Ejercicio Físico , Fémur/metabolismo , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteogénesis , Proteínas Adaptadoras Transductoras de Señales , Adulto , Biomarcadores/sangre , Marcadores Genéticos , Humanos , Masculino , Factores de TiempoRESUMEN
AIM: We hypothesized that 4 days of normal daily activity after 21 days of experimental bed rest (BR) will not reverse BR induced impaired glucose tolerance. DESIGN: Glucose tolerance of seven male, healthy, untrained test subjects (age: 27.6 (3.3) years (mean (SD)); body mass: 78.6 (6.4) kg; height: 1.81 (0.04) m; VO2 max: 39.5 (5.4) ml/kg body mass/min) was studied. They stayed twice in the metabolic ward (crossover design), 21 days in bed and 7 days before and after BR each. Oral glucose tolerance tests were applied before, on day 21 of BR, and 5 and 14 days after BR. RESULTS: On day 21 of BR, AUC(120 min) of glucose concentration was increased by 28.8 (5.2)% and AUC(120 min) of insulin by 35.9 (10.2)% (glucose: P < 0.001; insulin: P = 0.02). Fourteen days after BR, AUC(120 min) of serum insulin concentrations returned to pre-bed-rest concentrations (P = 0.352) and AUC(120 min) of glucose was still higher (P = 0.038). Insulin resistance did not change, but sensitivity index was reduced during BR (P = 0.005). CONCLUSION: Four days of light physical workload does not compensate inactivity induced impaired glucose tolerance. An individually tailored and intensified training regime is mandatory in patients being in bed rest to get back to normal glucose metabolism in a reasonable time frame.
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Reposo en Cama , Intolerancia a la Glucosa/fisiopatología , Adulto , Glucemia/metabolismo , Intolerancia a la Glucosa/sangre , Prueba de Tolerancia a la Glucosa , Humanos , MasculinoRESUMEN
The absence of mechanical loading leads to a prompt increase in bone resorption measured by bone resorption markers. There is high potential that vibration training can positively influence bone metabolism in immobilized subjects, reduce the increase in osteoclastic activity and increase bone formation processes. We investigated whether vibration training at 20 Hz with an amplitude of 2-4 mm influences bone metabolism during immobilization. Eight male subjects (26.4 ± 4.9 years; 78.1 ± 9.5 kg) performed a 14 day bed rest in 6°-head down tilt (HDT). Subjects received vibration training for 2 × 5 min/day or a control intervention without vibration (crossover design). Calcium excretion and bone resorption markers C-telopeptide (CTX) and N-telopeptide (NTX) were analyzed from 24 h urine samples. Bone formation markers, bone alkaline phosphatase (bAP) and procollagen-N propeptide (PINP) were analyzed from fasting blood samples. Our results show an increase in bone resorption very early during HDT bed rest in both interventions (CTX: p < 0.01; NTX: p < 0.001). Vibration training did not have any different effect on bone resorption markers (CTX: p = 0.10; NTX: p = 0.58), bone formation markers (PINP: p = 0.21; bAP: p = 0.12) and calcium excretion (p < 0.64) compared to the control condition. Mere vibration training with 20 Hz for 2 × 5 min/day does not prevent increase in bone resorption as measured with the described methods in our short-term HDT bed rest.
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Reposo en Cama/efectos adversos , Resorción Ósea/metabolismo , Huesos/metabolismo , Calcio/metabolismo , Vibración , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/metabolismo , Calcio/sangre , Calcio/orina , Estudios Cruzados , Humanos , MasculinoRESUMEN
We examined, in immobilization, the effect of a diet high in sodium chloride (NaCl) on bone markers, nitrogen balance, and acid-base status. Eight healthy male test subjects participated in a 14-day head-down-tilt bed rest (HDBR) study. During the bed rest period they received, in a randomized crossover design, a high (7.7 meq Na(+)/kg body wt per day) and a low (0.7 meq Na(+)/kg body wt per day) NaCl diet. As expected, 24-h excretion of urinary calcium was significantly greater in the high-NaCl-intake HDBR phase than in the low-NaCl-intake HDBR phase (P < 0.001). High NaCl intake caused a 43-50% greater excretion of the bone resorption markers COOH- (CTX) and NH(2)- (NTX) terminal telopeptide of type I collagen in HDBR than low NaCl in HDBR (CTX/NTX: P < 0.001). Serum concentrations of the bone formation markers bone-specific alkaline phosphatase (bAP) and NH(2)-terminal propeptide of type I procollagen (PINP) were identical in both NaCl intake phases. High NaCl intake led to a more negative nitrogen balance in HDBR (P < 0.001). Changes were accompanied by increased serum chloride concentration (P = 0.008), reduced blood bicarbonate (P = 0.017), and base excess (P = 0.009) whereas net acid excretion was lower during high than during low NaCl intake in immobilization (P < 0.001). High NaCl intake during immobilization exacerbates disuse-induced bone and muscle loss by causing further protein wasting and an increase in bone resorption. Changes in the acid-base status, mainly caused by disturbances in electrolyte metabolism, seem to determine NaCl-induced degradation processes.
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Resorción Ósea/inducido químicamente , Resorción Ósea/etiología , Huesos/metabolismo , Inclinación de Cabeza/efectos adversos , Inclinación de Cabeza/fisiología , Proteínas/metabolismo , Cloruro de Sodio Dietético/farmacología , Equilibrio Ácido-Base/efectos de los fármacos , Equilibrio Ácido-Base/fisiología , Adulto , Biomarcadores , Análisis de los Gases de la Sangre , Huesos/efectos de los fármacos , Calcio/sangre , Calcio/orina , Dieta , Humanos , Masculino , Nitrógeno/metabolismo , Hormona Paratiroidea/sangre , Sodio/sangre , Sodio/orinaRESUMEN
OBJECTIVE: Immobilization and space flight are causes of disuse osteoporosis. Increasing calcium intake may counteract this disuse-induced bone loss. METHODS: We conducted two bedrest experiments (crossover design: bedrest versus ambulatory control) in a metabolic ward, studying the effect of 1000 mg/d of calcium intake (study A, length of intervention 14 d) compared with that of a high calcium intake of 2000 mg/d (study B, 6 d) on markers of bone turnover. Both studies were randomized, controlled studies with the subjects staying under well-controlled environmental conditions (study A, 9 male subjects, age 23.6+/-3.0 y; study B, 8 male subjects, age 25.5+/-2.9 y). Blood was drawn to analyze serum calcium, parathyroid hormone, procollagen type I C-terminal propeptide, and bone alkaline phosphatase. Urine (24-h) was collected for analysis of calcium, C-terminal telopeptide of collagen type I, and N-terminal telopeptide of collagen type I. RESULTS: In both studies, serum calcium levels remained unchanged. Procollagen type I C-terminal propeptide was lower (P=0.03) in the bedrest phase than in the ambulatory phase in study A and tended to be lower (P=0.08) in bedrest in study B, whereas bone alkaline phosphatase was not affected in either study. Urinary calcium excretion was greater during bedrest than during the ambulatory phase (study A, P=0.005; study B, P=0.002). C-terminal telopeptide of collagen type I excretion was also greater during bedrest in both studies (study A, P<0.001; study B, P<0.001). CONCLUSION: Doubling calcium intake to 2000 mg/d does not prevent increased bone resorption induced by bedrest.
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Reposo en Cama , Remodelación Ósea/efectos de los fármacos , Calcio de la Dieta/administración & dosificación , Adulto , Fosfatasa Alcalina/sangre , Huesos/enzimología , Calcio/sangre , Calcio/orina , Colágeno Tipo I/orina , Estudios Cruzados , Humanos , Masculino , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/orina , Péptidos/orina , Procolágeno/sangre , Procolágeno/orinaRESUMEN
Contrasting data are published on the effects of high salt intake (between 300 and 660 mmol/d) on Na balance and fluid retention. In some studies high levels of NaCl intake (400, 440, 550 and 660 mmol/d) led to positive Na balances without fluid retention. To test the relevance of different baseline NaCl intake levels on changes in metabolic water, Na, K, chloride and acid-base balance, a 28 d clinical trial ('Salty Life 6') was carried out in a metabolic ward. Nine healthy male volunteers (aged 25.7 (SD 3.1) years; body mass (BM) 71.4 (SD 4.0) kg) participated in the present study. Four consecutive levels of NaCl intake: low (6 d, 0.7 mmol NaCl/kg BM per d), average normal (6 d, 2.8 mmol NaCl/kg BM per d), high (10 d, 7.7 mmol NaCl/kg BM per d), and low again (6 d, 0.7 mmol NaCl/kg BM per d) were tested. Urine osmolality, extracellular volume (ECV) and plasma volume (PV), cumulative metabolic Na, K, chloride and fluid balances, mRNA expression of two glycosaminoglycan (GAG) polymerisation genes, capillary blood pH, bicarbonate and base excess were measured. During average normal NaCl intake, 193 (SEM 19) mmol Na were retained and ECV (+2.02 (SEM 0.31) litres; P<0.001) and PV (+0.57 (SEM 0.13) litres; P<0.001) increased. During high NaCl intake, 244 (SEM 77) mmol Na were retained but ECV did not increase (ECV -0.54 (SEM 0.30) litres, P=0.+89; PV +0.27 (SEM 0.25) litres, P=0.283). mRNA expression of GAG polymerisation genes increased with rise in NaCl intake, while pH (P<0.01) and bicarbonate (P<0.001) levels decreased. We conclude that a high NaCl intake may increase GAG synthesis; this might play a role in osmotically inactive Na retention in humans.
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Equilibrio Ácido-Base/efectos de los fármacos , Agua Corporal/metabolismo , Cloruro de Sodio Dietético/administración & dosificación , Equilibrio Ácido-Base/fisiología , Adulto , Electrólitos/metabolismo , Espacio Extracelular/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glicosaminoglicanos/biosíntesis , Humanos , Masculino , Concentración Osmolar , Volumen Plasmático/efectos de los fármacos , ARN Mensajero/genética , Sodio/sangre , Sodio/orina , Cloruro de Sodio Dietético/farmacología , Micción/efectos de los fármacos , Adulto JovenRESUMEN
Previously published data (J Bone Miner Res (2005); 20: 471) did not give evidence that the administration of the nitric oxide precursor L-arginine increases bone formation and decreases bone resorption in postmenopausal women. Data of this trial were reanalysed for putative effects of L-arginine on muscle mass and muscular function. Therefore, 11 females of the former study group (n=15; age 54.5+/-4.1 years; daily oral administration of 18 g L-arginine hydrochloride (equivalent of 14.2 g L-arginine) over 6 months) and 12 females of the control group (n=15; age 55.3+/-4.4 years; daily administration of 18 g dextrose over 6 months) were analysed for biomechanical parameters (MIGF, maximal isometric grip force; PJF, peak jump force; PJP, peak jump power) and for the cross-sectional muscle area (MA) and fat area (FA) at forearm and leg (calf) measured by peripheral quantitative computed tomography. The study was performed in a double-blind design. The assessment of muscular and biomechanical parameters was undertaken before and after 6 months of L-arginine versus placebo administration. L-arginine-supplemented females had a significant increase of PJF/kg in comparison with the control group. PJP/kg, MIGF, MA and FA were not significantly influenced by the administration of L-arginine. In conclusion, the administration of L-arginine increased maximal force in mechanographic analyses and may prevent a decline of muscle force in postmenopausal women.
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Arginina/administración & dosificación , Contracción Isométrica/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Posmenopausia/fisiología , Antropometría , Femenino , Fuerza de la Mano/fisiología , Humanos , Contracción Isométrica/fisiología , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Músculo Esquelético/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Bone loss associated with disuse during bed rest (BR), an analog of space flight, can be attenuated by exercise. In previous studies, the efficacy of either aerobic or resistive exercise countermeasures has been examined separately. We hypothesized that a regimen of combined resistive and aerobic exercise during BR would prevent bone resorption and promote bone formation. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 degrees head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) performed no countermeasure. Exercise subjects (EX, n=8) participated in an exercise program during BR, alternating between supine treadmill exercise within lower body negative pressure (3-4 d wk(-1)) and flywheel resistive exercise (2-3 d wk(-1)). By the last week of BR, excretion of helical peptide (CON, 79%+/-44 increase; EX, 64%+/-50, mean+/-SD) and N-terminal cross-linking telopeptide (CON, 51%+/-34; EX, 43%+/-56), markers of bone resorption, were greater than they were before BR in both groups (P<0.05). However, serum concentrations of the bone formation marker procollagen type I N propeptide were greater in EX than CON throughout and after bed rest (P<0.05), while concentrations of the bone formation marker bone alkaline phosphatase tended to be greater in EX than CON. Dual-energy X-ray absorptiometry results indicated that the exercise treatment significantly (P<0.05) attenuated loss of hip and leg bone mineral density in EX compared to CON. The combination of resistive and aerobic exercise did not prevent bone resorption but did promote bone formation, and helped mitigate the net bone loss associated with simulated microgravity.
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Reposo en Cama/efectos adversos , Resorción Ósea , Ejercicio Físico , Presión Negativa de la Región Corporal Inferior , Medidas contra la Ingravidez , Simulación de Ingravidez , Adulto , Biomarcadores/metabolismo , Densidad Ósea , Dieta , Terapia por Ejercicio , Femenino , HumanosRESUMEN
UNLABELLED: Stepwise increase in NaCl intake in healthy male test subjects led to a low-grade metabolic acidosis. This was most likely the cause for increased bone resorption during high sodium chloride intake, as determined by analyzing bone resorption markers. INTRODUCTION: We examined the effect of increased dietary sodium chloride (NaCl) on bone metabolism and acid-base balance. MATERIALS AND METHODS: Subjects were nine healthy men (mean age, 25.7 +/- 3.1 yr; mean body weight [BW], 71.5 +/- 4.0 kg). During the first period (6 days), subjects received 0.7 mEq NaCl/kg BW per day (phase 1), during the second period (6 days) 2.8 mEq NaCl/kg BW per day (phase 2), during the third period (10 days) 7.7 mEq NaCl/kg BW per day (phase 3), and during the fourth period (6 days) 0.7 mEq NaCl/kg BW per day (phase 4). RESULTS: Twenty-four-hour urinary excretion of calcium and sodium rose significantly with increasing NaCl intake (p < 0.001 for both). Urinary excretion of bone resorption markers C- and N-terminal telopeptide of type I collagen (CTX, NTX) increased from phase 2 to phase 3 (CTX, p = 0.013; NTX, p < 0.001) and decreased from phase 3 to phase 4 (CTX, p < 0.001; NTX, p = 0.002). Bone formation markers N-terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin remained unchanged from low to high NaCl intake. Blood pH levels decreased (p = 0.04) between phases 1 and 3. Blood bicarbonate (HCO(3)(-)) and base excess (BE) decreased from phases 1 to 3 (p < 0.001 for both) and from phases 2-3 (HCO(3)(-), p = 0.003; BE, p = 0.015). Nearly all bone resorption markers and acid-base variables reached their baseline levels in phase 4. CONCLUSIONS: We conclude that low-grade metabolic acidosis may be the cause of NaCl-induced exaggerated bone resorption.
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Acidosis/fisiopatología , Resorción Ósea/inducido químicamente , Cloruro de Sodio/toxicidad , Equilibrio Ácido-Base , Adulto , Resorción Ósea/metabolismo , Calcio/sangre , Humanos , Masculino , Hormona Paratiroidea/sangreRESUMEN
We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6 degrees head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results--pronounced rise of bone resorption markers--that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.
Asunto(s)
Reposo en Cama , Resorción Ósea/patología , Calcio/sangre , Calcio/orina , Inclinación de Cabeza , Osteoclastos/fisiología , Adulto , Biomarcadores de Tumor/orina , Calcio de la Dieta , Colágeno/orina , Colágeno Tipo I , Estudios Cruzados , Dieta , Humanos , Masculino , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Péptidos/orina , Procolágeno/sangre , Factores de Tiempo , Simulación de IngravidezRESUMEN
UNLABELLED: NO is an important regulator of bone turnover. L-Arginine, the natural precursor of NO, can enhance NO production. However, no effect of L-arginine hydrochloride supplementation was found on bone metabolism or on BMD, bone mass, or bone structure of healthy postmenopausal women. INTRODUCTION: Recent studies indicate that NO exerts an anabolic effect on bone cell activity. The NO level of the human body can be elevated by administering pharmacological NO donors. Animal studies and the first human trial showed that NO donor administration had a positive effect on bone formation and a negative effect on bone resorption. L-arginine, the natural precursor of NO, can enhance NO production. This study was conducted to examine the effect of an oral L-arginine supplement on bone metabolism of healthy postmenopausal women. MATERIALS AND METHODS: The participants in this study were 30 healthy, age-matched postmenopausal women, divided into two groups. For 6 months, one group (54.5 +/- 4.1 years; 66.3 +/- 10.5 kg) received a daily oral supplement with 18 g L-arginine hydrochloride (14.8 g free L-arginine). The other 15 volunteers (55.3 +/- 4.4 years; 64.2 +/- 9.1 kg) received 18 g dextrose as a placebo. To verify compliance, 24-h urinary excretion of nitrogen was analyzed for 2 consecutive days at baseline and after 2, 4, and 6 months. At baseline and after 2, 4, and 6 months of supplementation, blood was drawn for analysis of insulin-like growth factor-I (IGF-I) and biomarkers of bone metabolism. At baseline, after 6 months, and after 1 year, pQCT measurements were performed at trabecular and cortical sites of the radius and tibia. The two groups of subjects were compared by repeated measures ANOVA. RESULTS: As expected, in the group with L-arginine hydrochloride supplementation, nitrogen excretion rose, and in the placebo group, it remained constant. Only bone formation marker, procollagen type I propeptides (PICP), increased significantly (p < 0.05) after 6 months of L-arginine supplementation. The results from pQCT showed no significant changes at any site in either group. No significant change in IGF-I concentration, which might have been caused by the L-arginine hydrochloride supplementation, was evident. CONCLUSIONS: We conclude from these results that supplementation with L-arginine hydrochloride is not effective for improving bone mass in humans.
Asunto(s)
Arginina/administración & dosificación , Remodelación Ósea/efectos de los fármacos , Suplementos Dietéticos , Osteoporosis Posmenopáusica/prevención & control , Posmenopausia/efectos de los fármacos , Administración Oral , Anciano , Remodelación Ósea/fisiología , Femenino , Humanos , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Posmenopausia/metabolismoRESUMEN
The aim of the study was to analyze the kinetics of short-term changes in bone turnover. We studied in a randomized crossover design the effects of 6 days of bed rest on eight healthy male subjects (mean body wt: 70.1 +/- 5.7 kg; mean age: 25.5 +/- 2.9 yr). The metabolic ward period was divided into three parts: 4 ambulatory days, 6 days of either bed rest or non-bed rest periods, and 1 recovery day. The diet was identical in both bed rest and non-bed rest phases. Continuous urine collection started on the first day in the metabolic ward to analyze excretion of bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX), creatinine, urea, and 3-methylhistidine. On the second ambulatory day and on the fifth day of bed rest or during the non-bed rest phase, blood was drawn to analyze bone formation markers and amino acid concentrations. Urinary calcium excretion was increased as early as the first day of bed rest (P < 0.01). CTX and NTX excretion stayed unchanged during the first 24 h of bed rest compared with the non-bed rest period. However, already on the second day, both resorption markers had increased significantly. NTX excretion increased by 28.7 +/- 14.0% (P < 0.01), whereas CTX excretion rose by 17.8 +/- 8.3% (P < 0.001). Creatinine, urea, and 3-methylhistidine excretion did not change. We conclude that 24 h of bed rest are sufficient to induce a significant rise in osteoclast activity in healthy subjects.