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Ohshima, Hiroshi

Publications and source records attributed to Ohshima, Hiroshi.

Update of the Bisphosphonate ISS Flight Experiment

The bisphosphonate study is an international collaboration between the NASA and JAXA space agencies to investigate the potential value of antiresorptive drugs to mitigate the well-established bone changes associated with long-duration spaceflight. Our hypothesis is that an antiresorptive drug in combination with in-flight exercise will ameliorate bone loss and hypercalcuria during long-duration spaceflight. We have completed data analysis for 7 crewmembers treated with alendronate during flight and 3 of 10 controls without treatment. We previously reported the pre/postflight changes in bone density and the pre versus in-flight changes in various biomarkers in crewmembers taking alendronate during flight. The purpose of this report is to compare these results with the 12- month follow-up data. The table below presents these data as a percentage change from baseline either immediately postflight or in-flight (biochemical markers) with a 1-year follow-up.

LeBlanc, Adrian

Bisphosphonate ISS Flight Experiment

The bisphosphonate study is a collaborative effort between the NASA and JAXA space agencies to investigate the potential for antiresorptive drugs to mitigate bone changes associated with long-duration spaceflight. Elevated bone resorption is a hallmark of human spaceflight and bed rest (common zero-G analog). We tested whether an antiresorptive drug in combination with in-flight exercise would ameliorate bone loss and hypercalcuria during longduration spaceflight. Measurements include DXA, QCT, pQCT, and urine and blood biomarkers. We have completed analysis of 7 crewmembers treated with alendronate during flight and the immediate postflight (R+<2 week) data collection in 5 of 10 controls without treatment. Both groups used the advanced resistive exercise device (ARED) during their missions. We previously reported the pre/postflight results of crew taking alendronate during flight (Osteoporosis Int. 24:2105-2114, 2013). The purpose of this report is to present the 12-month follow-up data in the treated astronauts and to compare these results with preliminary data from untreated crewmembers exercising with ARED (ARED control) or without ARED (Pre-ARED control). Results: the table presents DXA and QCT BMD expressed as percentage change from preflight in the control astronauts (18 Pre-ARED and the current 5 ARED-1-year data not yet available) and the 7 treated subjects. As shown previously the combination of exercise plus antiresorptive is effective in preventing bone loss during flight. Bone measures for treated subjects, 1 year after return from space remain at or near baseline values. Except in one region, the treated group maintained or gained bone 1 year after flight. Biomarker data are not currently available for either control group and therefore not presented. However, data from other studies with or without ARED show elevated bone resorption and urinary Ca excretion while bisphosphonate treated subjects show decreases during flight. Comparing the two control groups suggests significant but incomplete improvement in maintaining BMD using the newer exercise protocols compared to earlier resistive exercise protocols. Quantitative characterization of this improvement requires additional measurements in the ARED control group that we are currently collecting. In conclusion, these results indicate that an antiresorptive may be an effective adjunct to exercise during long-duration spaceflight.

LeBlanc, Adrian

Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there is still high variability in individual response. Three additional crewmembers have been recruited to participate in this experiment, with expected completion in late 2011.

LeBlanc, Adrian

Preliminary Results of Bisphosphonate ISS Flight Experiment

Bone loss has been recognized as a potential problem from the beginning of human spaceflight. With the spaceflight missions lasting 6 months to potentially 3 years or longer this issue has assumed increased significance. Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from the total skeleton and critical sub-regions. The most important losses are from the femoral hip averaging about -1.6%/mo integral to -2.3%/mo trabecular BMD. Importantly these studies have documented the wide range in individual response from -0.5 to -5%/mo in BMD. Given the small size of any expedition crew, the wide range of responses has to be considered in the implementation of any countermeasure. Assuming that it is unlikely that the susceptibility for bone loss in any given crewmember will be known, a suite of bone loss countermeasures will likely be needed to insure protection of all crewmembers. The hypothesis for this experiment is that the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss and strength and will reduce renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the total hip BMD were significantly changed from -1.1 0.5%/mo to 0.04 0.3%/mo (p<0.01); QCT-determined trabecular BMD of the total hip was significantly changed from -2.3 1.0%/mo to -0.3 1.6%/mo (p<0.01). Significance was calculated from a one-tailed t test. While these results are encouraging, the current n (4) is small, and the large SDs indicate that while the means are improved there is still high variability in individual response. Four additional crewmembers have been recruited to participate in this experiment, with expected completion of these flights by late 2011.

LeBlanc, Adrian

Exercise load index and changes in body weight during long-duration confinement in an isolated environment

PURPOSE: The objectives of this project were to investigate exercise load and body weight related to long-duration confinement in a closed environment simulating ISS flight conditions, and to evaluate subjects' motivation to continue the experiment and their adaptation to isolation. METHODS: Four Russian male subjects participated in a 240-d experiment (Group I), and four subjects (three male subjects and one female subject) from Austria, Canada, Japan, and Russia participated in a 110-d experiment (Group II). Exercise load was estimated during confinement using a modified Rating of Perceived Exertion scale. Free reports were used to determine subjects' motivation. Body weight was measured before, during, and after confinement. RESULTS: Group I achieved their lowest exercise loads during their first month of isolation; problems with adaptation to the isolation environment were also reported during this first month. Group II exercise load was significantly lower in the second month due to crewmember problems; loss of motivation could be noted from their free reports. The subject with the lowest exercise load retired from the isolation experiment earlier than scheduled. Exercise load was not correlated with prior exercise habits. Significant differences in body weight was observed between group I and II and between Russian and non-Russian subjects. One subject in Group I experienced a significant increase in his body weight. CONCLUSION: Exercise load may be a good indicator for adaptation problems and motivation changes in closed environments. Immobility, lack of space, and smoking cessation in general did not induce significant body weight changes.

Exercise/physiology

Physiological changes, sleep, and morning mood in an isolated environment

BACKGROUND: Previous isolation studies have shown increased 24-h urine volumes and body weight gains in subjects. This project examined those and other physiological variables in relationship to sleep motor activity, subjective sleep quality, mood, and complaints during confinement. METHODS: Six male and two female subjects lived for 7 d in the National Space Development Agency of Japan's isolation chamber, which simulates the interior of the Japanese Experiment Module. Each 24-h period included 6 h of sleep, 3 meals, and 20 min of exercise. Each morning, subjects completed Sleep Sensation and Complaint Index questionnaires. Catecholamine and creatinine excretion, urine volume, and body weight were measured on the 2 d before and 2 d after confinement, and sleep motor activity was measured during confinement. RESULTS: Confinement produced no significant change in body weight, urine volume, or questionnaire results. In contrast, epinephrine, norepinephrine, and sleep motor activity exhibited significant differences during confinement (p < 0.05). Higher nocturnal norepinephrine excretion correlated with higher sleep motor activity. CONCLUSION: The 24-h epinephrine values were slightly higher than normal throughout the experiment, but lower than for subjects working under time-stress. High sympathetic activity (as indicated by norepinephrine) may have interfered with sleep.

NASA Discipline Space Human Factors