Engineering topics
Kohri, Kenjiro
Publications and source records attributed to Kohri, Kenjiro.
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.
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.
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.
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.