D
Bone Fracture Risk Associated with Prolonged Exposure to Microgravity

The incorporation of evidenced-based data into risk assessment is necessary to ensure that the Bioastronautics Roadmap (BR) evolves and remains current. Bone loss is a major risk that has been the focus of considerable research and countermeasure development at the National Aeronautics and Space Administration (NASA). However, the lack of evidence-based data for estimating the fracture risk associated with prolonged exposure to microgravity is a deficiency that compromises the assessment of countermeasure effectiveness. This is evident when one attempts to apply existing data to the following BR risk areas: (1) fracture risk assessment during prolonged microgravity exposure combined with a period of reduced-gravity exposure (e.g., during Mars exploration) and (2) fracture risk that is age-related due to early-onset osteoporosis as a consequence of bone loss following microgravity or reduced-gravity exposure.

Evidence-based data relating dual energy X-ray absorptiometry (DXA) bone density measurements to fracture risk do not exist for populations of men or women in the age range 35–50 years. Data do relate bone density measured by DXA to fracture risk, but for older, less physically fit populations. The World Health Organization (WHO) has defined “osteoporosis” as bone mineral density (BMD) greater than −2.5 standard deviations (SD) below age of peak bone density in white women (WHO, 1994). Fracture risk was estimated to increase 2.5-fold for each SD below adult peak bone density. However, data for men and non-white women were not included.

Melton et al. (1998) presented age-adjusted odds ratios for osteoporotic



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A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA’s Bioastronautics Roadmap D Bone Fracture Risk Associated with Prolonged Exposure to Microgravity The incorporation of evidenced-based data into risk assessment is necessary to ensure that the Bioastronautics Roadmap (BR) evolves and remains current. Bone loss is a major risk that has been the focus of considerable research and countermeasure development at the National Aeronautics and Space Administration (NASA). However, the lack of evidence-based data for estimating the fracture risk associated with prolonged exposure to microgravity is a deficiency that compromises the assessment of countermeasure effectiveness. This is evident when one attempts to apply existing data to the following BR risk areas: (1) fracture risk assessment during prolonged microgravity exposure combined with a period of reduced-gravity exposure (e.g., during Mars exploration) and (2) fracture risk that is age-related due to early-onset osteoporosis as a consequence of bone loss following microgravity or reduced-gravity exposure. Evidence-based data relating dual energy X-ray absorptiometry (DXA) bone density measurements to fracture risk do not exist for populations of men or women in the age range 35–50 years. Data do relate bone density measured by DXA to fracture risk, but for older, less physically fit populations. The World Health Organization (WHO) has defined “osteoporosis” as bone mineral density (BMD) greater than −2.5 standard deviations (SD) below age of peak bone density in white women (WHO, 1994). Fracture risk was estimated to increase 2.5-fold for each SD below adult peak bone density. However, data for men and non-white women were not included. Melton et al. (1998) presented age-adjusted odds ratios for osteoporotic

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A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA’s Bioastronautics Roadmap fracture per 1 SD decrease in BMD or in bone mineral apparent density (BMAD), by skeletal site, for individuals in Rochester, Minnesota. Men were 22–90 years of age (n = 348) and women were 21–98 years of age (n = 351). Per 1 SD decrease in BMD at total hip, for 29- to 49-year-old men, odds ratios were 1.38, 1.12, and 1.17 for total hip, femoral neck, and anterior–posterior (AP) spine scans, respectively, and 1.45 for total wrist. For women ages 20–49 years, odds ratios were 2.44, 1.72, and 1.59 for total hip, femoral neck, and AP spine scans, respectively, and 1.56 for total wrist. It is noted that unlike the astronaut crew, the baseline fracture rate was relatively increased in this community-based population. For men, total hip BMD was 1.061–0.140 g/cm2, and for premenopausal women, mean total hip BMD was 0.941–0.124 g/cm2. After adjusting for age, total hip BMD was the best predictor of fracture risk in women. In men, BMD at the wrist was the stronger predictor of fracture risk. This experience should be compared to existing data on baseline BMD and bone loss in the astronaut population. It is widely appreciated that an assessment of fracture risk based solely on DXA BMD measurement is inadequate. Susceptibility to fracture at any level of bone mass is determined by bone density measurement and by the structural integrity of bone, which cannot be measured accurately with existing technology. The application of engineering principles to derive indirect assessments of bone strength—bone section modulus and buckling ratio (Beck et al., 2001; Kaptoge et al., 2003; Melton et al., 2005)—represents an advance in the field. Quantitative computed tomographic (QCT)– derived measurements of bone density and bone geometry in 14 astronauts after four to six months on the International Space Station (ISS) indicated a decline in bone density and parameters of bone strength (i.e., strength index, compressive strength indexes) in proximal hip and vertebral body (Lang et al., 2004). Consistent with earlier DXA studies involving Mir cosmonauts, bone was lost at rates of 0.8–0.9 percent per month at the spine and 1.2–1.5 percent per month at the hip. Although both cortical and trabecular bone declined, the percent loss in trabecular bone was greatest in the hip: proximal femur, 2.2–2.7 percent per month. As noted above, Lang et al. pointed out that the various bone strength indexes have not been validated as predictors of fracture risk and that the number of ISS subjects was small. Although presenting data were derived by a sensitive technique—volumetric QCT—it is likely that more accurate data relating bone loss to strength parameters will be derived in the near future from

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A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA’s Bioastronautics Roadmap methods such as high-resolution anisotopic ultrasound or micromagnetic resonance imaging. Thus, current estimates of fracture risk applied to space flight are inadequate for the following reasons: They are based on DXA data derived from older populations; these data could be applied to the older astronaut population but are not adequate for younger populations. Existing DXA data do not adequately address the problem of site specificity for bone strength, which is significant for estimating flight-related fracture risk. The contribution of prolonged residence in a reduced-gravity environment to either lessening bone loss or promoting bone formation immediately following extended microgravity exposure during transit cannot be assessed at this time. The added impact of a return flight from Mars on site-specific bone loss and fracture risk or the individual ability to regain bone mass at 1 × g (as the astronaut ages) cannot be determined. An evidenced-based assessment of bone loss and fracture risk (BR Risk 1, impaired fracture healing, and BR Risk 2, injury to joints and intervertebral discs) should be made using a multivariate analysis of existing flight-derived data on bone density and individual-specific characteristics that contribute to bone strength. The above risks are important during flight because of slow or poorly healing fractures in a microgravity environment and the need to anticipate these problems for medical care during flight. In addition, these risks are important because of back pain due to changes in intervertebral discs and the possibility of damage even after return from flight. As an example, factors for which evidence-based data can be obtained include the following: Age: susceptibility to fracture increases with increasing age. Prior history of fracture: prior fracture increases risk for future fracture. Family history of multiple fractures. Gender: men may fracture at greater BMD values than women (site specificity has not been determined, and the observation is limited in the numbers surveyed). Initial BMD: fracture rate increases as DXA BMD decreases.

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A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA’s Bioastronautics Roadmap Return to baseline following successive flights as an indication of the resilience of bone-forming systems: failure to regain baseline BMD would presumably increase fracture risk when repeated microgravity exposure is experienced. Nutritional factors during and post-flight: maintenance of bone mass would be altered with prolonged negative intake of mineral and protein dietary components. Impact of exercise activity during and after flight: compliance with exercise and the effectiveness of specific exercise programs during and after flight impact bone mass. Rate and extent of bone loss on prior flights: there are no evidence-based data related to fracture risk for this factor. Alterations in structural and geometric parameters that could have iterative effects on bone strength occurring during successive flights. Duration of microgravity or reduced-gravity exposure: it has been demonstrated that six-month microgravity exposure reduces bone mass in most astronauts; however major fractures have not been reported, nor has the occurrence of stress fractures following return to 1g. Fracture risk assessment during and following extended microgravity exposure requires the utilization of existing astronaut data as well as the expansion of current methods for measuring bone mass and bone strength. The dearth of data related to the microgravity environment encountered during extended-duration space flight suggests a need for increased research to support evidence-based decision making regarding these subjects. REFERENCES Beck TJ, Oreskovic TL, Stone KL, Ruff CB, Ensrud K, Nevitt MC, Genant HK, Cummings SR. 2001. Structural adaptation to changing skeletal load in the progression toward hip fragility: the study of osteoporotic fractures. J. Bone Min. Res. 16(6): 1108–1119. Kaptoge S, Dalzell N, Loveridge N, Beck TJ, Khaw KT, Reeve J. 2003. Effects of gender, anthromorphic variables and aging on the evolution of hip strength in men and women over 65. Bone 32: 561–570. Lang T, LeBlanc A, Evans H, Ying L, Genant H, Yu A. 2004. Cortical and trabecular bone mineral loss from the spine and hip in long-duration space flight. J. Bone Min. Res. 19(6): 1006–1012.

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A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA’s Bioastronautics Roadmap Melton LJ III, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL. 1998. Bone density and fracture risk in men. J. Bone Min. Res. 13(12): 1915–1923. Melton LJ III, Beck TJ, Amin S, Khosla S, Achenbach SJ, Oberg AL, Riggs BL. 2005. Contributions of bone density and structure to fracture risk assessment in men and women. Osteoporos. Int. Feb. 2. Abstract on-line [available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15688123]. Accessed 4/15/05. WHO (World Health Organization). 1994. Assessment of Fracture Risk and Its Application in Screening for Postmenopausal Osteoporosis. Technical Report Series 843. Geneva: World Health Organization.