Natalie Baecker

WISE-2005: Supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity☆

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.

Effects of artificial gravity during bed rest on bone metabolism in humans

We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6 degrees head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 G(z) at the heart, 2.5 G(z) at the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group (P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant (P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest.

Low-Grade Metabolic Acidosis May Be the Cause of Sodium Chloride-Induced Exaggerated Bone Resorption

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.

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

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.

The effect of L-arginine administration on muscle force and power in postmenopausal women.

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.

L-Arginine, the Natural Precursor of NO, Is Not Effective for Preventing Bone Loss in Postmenopausal Women†

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.

Short-term high dietary calcium intake during bedrest has no effect on markers of bone turnover in healthy men.

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.

How fast is recovery of impaired glucose tolerance after 21-day bed rest (NUC study) in healthy adults?

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, AUC120 min of glucose concentration was increased by 28.8 (5.2)% and AUC120 min of insulin by 35.9 (10.2)% (glucose: P < 0.001; insulin: P = 0.02). Fourteen days after BR, AUC120 min of serum insulin concentrations returned to pre-bed-rest concentrations (P = 0.352) and AUC120 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.

Effects of high-protein intake on bone turnover in long-term bed rest in women

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 groups 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.

Interactions between Artificial Gravity, Affected Physiological Systems, and Nutrition

Malnutrition, either by insufficient supply of some nutrients or by overfeeding has a profound effect on the health of an organism. Therefore, optimal nutrition is mandatory on Earth (1 g), in microgravity and also when applying artificial gravity to the human system. Immobilization like in microgravity or bed rest also has a profound effect on different physiological systems, like body fluid regulation, the cardiovascular, the musculoskeletal, the immunological system and others. Up to now there is no countermeasure available which is effective to counteract cardiovascular deconditioning (rf. Chapter 5) together with maintenance of the musculoskeletal system in a rather short period of time. Gravity seems therefore to be one of the main stimuli to keep these systems and application of certain duration of artificial gravity per day by centrifugation has often been proposed as a very potential countermeasure against the weakening of the physiological systems. Up to now, neither optimal intensity nor optimal length of application of artificial gravity has been studied sufficiently to recommend a certain, effective and efficient protocol. However, as shown in chapter 5 on cardiovascular system, in chapter 6 on the neuromuscular system and chapter 7 (bone and connective system) artificial gravity has a very high potential to counteract any degradation caused by immobilization. But, nutrient supply -which ideally should match the actual needs- will interact with these changes and therefore has also to be taken into account. It is well known that astronauts beside the Skylab missions- were and are still not optimally nourished during their stay in space (Bourland et al. 2000;Heer et al. 1995;Heer et al. 2000b;Smith et al. 1997;Smith & Lane 1999;Smith et al. 2001;Smith et al. 2005). It has also been described anecdotally that astronauts have lower appetites. One possible explanation could be altered taste and smell sensations during space flight, although in some early space flights no significant changes were found (Heidelbaugh et al. 1968;Watt et al. 1985). However, data from a recent head-down bed rest study showed significant decrease in smell sensation (Enck et al. unpublished data) suggesting that fluid shifts might have an impact. If this holds true and which has to be validated in further studies, this seems to play an important role for lowered food intake causing insufficient energy intake and subsequently insufficient supply of most of the macro- and micronutrients. Other nutrients are taken in excess, for example sodium. As it is very well known from daily food consumption especially premanufactured food with high salt content seems to be more palatable than that with low salt content. Salt also functions as preservation which is very important taking into account the space food system limitations (i.e., lack of refrigerators and freezers). The preference for food with high salt intake by astronauts might therefore very likely be caused by altered smell and taste sensations in microgravity.