specific high-priority research initiatives that are needed to sharpen and advance the science knowledge necessary for progress in the next decade. (It is important to note that certain topics that have a major impact across multiple physiological systems, such as nutrition, are in most cases not covered in this chapter, but rather in Chapter 7, which focuses on crosscutting issues.) Finally, in examining programmatic activities relevant to this chapter, and as discussed in the committee’s interim report to NASA,1 the AHB Panel was deeply concerned that NASA had severely reduced research initiatives in the life and physical sciences in the latter half of the past decade. In the panel’s view, this action has effectively paralyzed research initiatives previously recommended by National Research Council (NRC) study committees (as reflected by the relative paucity of publications since 2005 in recommended subject areas such as bone) and poses a daunting challenge to future administrations attempting to reverse the neglect and to accomplish the life and physical sciences research initiatives recommended in this report.

RESEARCH ISSUES

Risks for Bone Loss During Long-Duration Space Missions

The skeletal (bone) system provides the solid framework for humans and mammals to oppose gravity, and its fidelity in accomplishing this fundamental process has evolved over millions of years. Given this evolutionary role, it is not surprising that bone loss occurs in astronauts at a rate that is both substantial and progressive with time spent in microgravity.2-5 Accordingly, without appropriate countermeasures, spaceflight of 2 years or longer will present serious risks due to progressive bone fragility. Therefore, there is a need to adopt effective countermeasures that have been appropriately tested in relevant human and animal models. The 1998 NRC report A Strategy for Research in Space Biology and Medicine in the New Century6 recommended several experiments to address the problem of bone loss during spaceflight. At present, several key issues raised in the 1998 NRC report have not been addressed. For instance, the report recommended that genetically altered mice be used in flight experiments to investigate the molecular mechanisms of bone loss, yet these experiments have not been completed. The report also recommended that in-flight animal facilities should house 30 adult rats or mice, but the ISS can currently house only 6 mice (in the Mice Drawer System on the Italian Space Agency investigation). These recommendations should be implemented, and additional steps should be taken to advance research into bone loss in microgravity for the development of effective countermeasures.

Effects of Spaceflight Environment on the Structure and Function of Bone

Bone loss during spaceflight appears to be due primarily to increased resorption in load-bearing regions of the skeleton.7,8,9 There is also some evidence of a decrease in bone formation. The rate of bone loss in microgravity is roughly 10 times greater than the bone mineral density (BMD) loss per month that occurs in postmenopausal women on Earth who are not on estrogen therapy.10-13 Results from Skylab,14 Mir,15,16 the space shuttle,17 and the ISS18,19,20 missions have shown substantial areal and volumetric bone loss in critical regions such as the proximal femur and spine. The most accurate data, derived from quantitative computed tomography, have shown that spinal volumetric BMD was lost at a rate of 0.9 percent per month and total hip volumetric BMD was lost at rate of 1.4 percent per month; there was, however, considerable variability between individuals.21 Changes in bone strength (expressed as percentage loss) were much greater than changes in BMD.22

BMD lost in 6-month missions appears to be mostly reversible by 1,000 days after return to normal gravity (1 g).23,24 However, changes in bone structure are not reversible and seem to mimic changes in the elderly.25 An important question that remains unanswered is whether any loading that is performed by simply living and working in partial gravity—such as the 1/6 g of the Moon or the 1/3 g of Mars—will provide any protection from the bone loss that occurs in microgravity. Expert opinion as presented in a recent symposia is that it will not,26 although data from a partial-gravity mouse model is just becoming available.27

Animal Studies

Rodents have been flown on the Cosmos biosatellite28-33 and on space shuttle missions34-46 to measure bone loss. The most consistent finding was the striking decrease in bone formation with spaceflight, which stopped



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