SOURCE: Adapted from NASA, 2014.
RISK OF BONE FRACTURE DUE TO SPACEFLIGHT-INDUCED CHANGES TO BONE
Bones break when an applied force exceeds bone strength. Thus, a fracture may occur—and frequently does—even in young healthy bones if they are subjected to sufficient force. When bones have been weakened by osteoporosis, the amount of force required to break them becomes significantly lower. The key force parameters relevant to bone fracture include the duration, direction, and onset of the applied force as well as the maximum load of the bone. Major factors influencing bone strength include bone density and architecture. Osteoporosis is commonly encountered and treated in terrestrial medicine, and in that context it is typically associated with hormonal deprivation (i.e., as often appears during menopause or in hypogonadal males), aging, or the administration of glucocorticoids or other medications. There is also a somewhat smaller body of literature and research pertaining to the osteoporosis induced by skeletal unloading, and to its diagnosis and treatment. In space, exposure to microgravity is associated with bone loss due primarily to the decreased formation of new bone and to changes in bone structure that may weaken bones (see the review of the NASA evidence report on osteoporosis that follows).
This report, Risk of Bone Fracture Due to Spaceflight-Induced Changes to Bone, discusses the evidence documenting losses in bone mineral density associated with microgravity (Sibonga et al., 2017a). It discusses mechanisms of fracture (concentrating primarily upon falls), the effect of fractional gravity (such as the moon or Mars) upon the consequences of a fall, and the possible ability of a space suit to alter the fracture risk associated with a fall. It applies a probabilistic risk measure, the “Factor of Risk,” to estimate the likelihood of a fracture.
Two terms that are used in terrestrial medicine that may be conceptually useful in the discussion of this report are fragility fracture and atypical fracture. Fragility fractures may occur when bone weakened by osteoporosis breaks more easily than expected. Atypical fractures are rare, and are associated with the long-term use of antiresorptive agents. These may become relevant if slow recovery from microgravity-induced bone loss requires prolonged therapy. A fragility fracture is judged to have occurred if an impact (such as a fall from a standing height) that would not normally be expected to cause a fracture does result in a fracture. An atypical fracture refers to a certain type of peculiar fracture (such as midshaft femur fractures) that has been reported after prolonged antiresorptive therapy despite recovery of bone mass as assessed by a DXA (dual-energy X-ray absorptiometry) scan. Atypical fractures provide evidence that a DXA measurement of bone density does not adequately address bone architecture and that information on other qualities of bone, such as composition and turnover, is needed to better understand and estimate bone strength and fracture risk. Other modalities, such as quantitative computed tomography (QCT) and magnetic resonance imaging (MRI), provide more information on bone architecture than DXA but are not as easily performed (particularly in flight). Both the development of osteoporosis and its evaluation are intimately linked to fracture risk. Issues regarding osteoporosis and its assessment are discussed in greater detail in the evidence report Risk of Early Onset Osteoporosis Due to Space Flight (Sibonga et al., 2017b) and in the committee’s review of that report later in this document. Atypical fractures, albeit rare, further raise the possibility that excessive reliance on antiresorptive therapy may not result in complete avoidance of fractures despite reassuringly good bone density measurements on DXA.
Does the Evidence Report Provide Sufficient Evidence, as Well as Sufficient Risk Context, That the Risk Is of Concern for Long-Term Space Missions?
Both the risk and the context are delineated. In Part II the evidence report acknowledges the uncertainties surrounding the microgravity-associated loss of bone mineral density (BMD) as measured by a DXA scan and the difficulties associated with that measurement, particularly during a mission (so as to allow the adjustment of countermeasures for an individual astronaut). It then goes on to state, “The risk of fracture during a mission cannot be estimated with any level of certainty until the probabilities of overloading bones during the missions are understood” (Sibonga et al., 2017a, p. 4). Thus, the context for concern is well stated.
The body of evidence in the report relates to observed changes in average bone mineral density (aBMD) using DXA. These changes, which are derived primarily from measurements before and after exposure to microgravity, demonstrate a variable pattern of loss and recovery among astronauts. The limitations of DXA, including the variability among individuals in DXA scores, are discussed in the evidence report on osteoporosis.
Much of the body of the report deals with the Factor of Risk index that assesses the ratio of applied load to the failure load of bone. The index incorporates the direction and magnitude of force into a probabilistic model that is as yet untested beyond low Earth orbit. The committee felt that this continued reliance on the Factor of Risk is a concerning oversimplification. The ratio of imposed load to fracture load misses many important factors. For example, when stating that the risk of fracture in low Earth orbit is negligible, the authors consider both the absence of fracture reports to date and the low loading imposed by a fall in reduced gravity. However, the latter ignores the risk associated with a sudden deceleration of the astronaut and the impact imposed by spacecraft acceleration, either during orbital maneuvers or docking or associated with landing on another surface (for further information see Caldwell et al., 2012). It also fails to consider the possibility of crush (due to inertia), collision, and the other types of injuries (with a fracture component) associated with heavy equipment operation.
A substantial concern about the report is the possibility of falsely assuming, based on the absence of fractures in past human spaceflight, that the risk of fractures in future missions is nil or negligible. In fact, the exposure to bone-breaking loads during falls or collisions is certainly
larger for unbalanced astronauts maneuvering on a planetary surface than for those working in microgravity.
Furthermore, a close examination of the Factor of Risk projections shows a significant chance of, for example, a wrist fracture occurring during a future Mars mission. Such a fracture may be sustained when an individual falls and puts out an arm to break the fall, thus sparing, perhaps, a femoral neck fracture. Fractures thus appear, even with this model, to be sufficiently likely to require effective management (Nelson et al., 2009).
Although there is an emphasis throughout the report on hip (femur) fracture due to falling, a relatively athletic individual may have time to throw out an arm and break the fall, thus, as previously noted, preventing a hip fracture but sustaining a fractured wrist instead (see, for example, Stepaniak et al., 2014). Similarly, there is a risk of rib or other fracture when an astronaut falls against or impacts a protruding object due to his or her own movement or from sudden lateral or vertical acceleration of the spacecraft, including elements of the spacesuit and its equipment.
The future risk of bone fracture will surely rise in the era of extensive human exploration of planets and return to the moon, and, later, in the era of working on other planetary bodies rather than merely visiting them. Adjusting to movement on a planetary body after transit in zero-G will require time and care that may, at least transiently, interfere with balance and thereby increase risk of falls and thus fractures (Chappell et al., 2017). In terrestrial medicine it is recognized that the risk of fractures in elderly patients is significantly higher in those with visual, proprioceptive, and neurovestibular issues. All of these sensory systems may be impaired in astronauts walking and working on a planetary body, under fractional gravity after a prolonged zero-G transit (Bloomberg et al., 2016). One look at an episode of repeated trips and falls during Apollo 17 shows that there is a risk of bone fracture that is incompletely understood (e.g., YouTube, 2007). Walking, running, or darting about in altered gravity is likely to lead to unexpected impacts and consequent bone fracture. The risk of impact (crush injuries) associated with operating machinery and moving large masses is mentioned, but insufficiently addressed.
There are post-flight concerns as well. The evidence report on osteoporosis (Sibonga et al., 2017b) clearly documents the observed changes in bone mineral density associated with exposure to microgravity, and, additionally, provides evidence that the bone density lost may not be regained even after 3 years of follow-up (Amin et al., 2010, 2011). Such
failure to regain lost bone mineral density may lead to an increased risk of fracture as astronauts age.
Does the Evidence Report Provide Evidence That the Named Gaps Are the Most Critical Presented?
The evidence report correctly identifies three critical gaps, to which the committee suggests adding others, below.
Are There Any Additional Gaps or Aspects to Existing Gaps That Are Not Addressed for This Specific Risk?
The committee considered the following additional gaps as significant:
- What is the best measure(s) of bone health for the astronaut population, both pre-flight and in flight?
- Is there a threshold for protection from bone loss as it is unlikely that the risk of bone loss will ever be zero? At what point are the pharmaceutical and/or exercise countermeasures considered adequate to reduce this risk?
- What are the maximum G-forces and force vectors that might precipitate a fracture during launch or landing at any phase of a beyond-Earth-orbit mission?
- What is the risk of fracture during exercise activity, including the ARED (advanced resistive exercise device)?
- What is the appropriate management of fractures that occur during a mission?
- What lessons can be learned from pharmacologic manipulation of bone metabolism to attempt to enhance fracture healing in osteoporotic adults in terrestrial medicine?
- What can be learned from the clinical history of osteoporosis and fractures in the quadriplegic/paraplegic population? Extensive data are available from bed-rest studies in healthy volunteers; however, these data could be supplemented by the clinical models and experience gained in fracture management of other populations with osteoporosis.
- What countermeasures should be investigated for extended-duration missions? Considering the risk as well as the benefit of using extensive resistive exercise as the primary microgravity
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countermeasure, should emphasis also be placed on alternative countermeasures for extended-duration missions?
- How can bone health be monitored during long-duration missions? Is urinary calcium excretion an adequate marker, or do other metrics need to be developed so that countermeasures can be tailored to the needs of each individual astronaut?
- How should countermeasures, including the use of anabolic or antiresorptive pharmaceuticals, be altered if deterioration in bone health measures or fracture occurs during a mission?
- What can be applied from bed-rest studies in humans and tail-suspended studies in rodents? How can these models be used to evaluate pharmacologic interventions?
- Can suit design help ameliorate fractures due to falls or collisions?
- What is the best way to immobilize a fracture so that an astronaut can continue mission-related activities including, if necessary, donning an extravehicular activity (EVA) suit?
Does the Evidence Report Address Relevant Interactions Among Risks?
The report clearly identifies the interaction between the risk of fracture and the risk of premature osteoporosis, which is the subject of a separate report. To the extent that calcium mobilized from the skeleton will be excreted in the urine, the changes that occur in bone are related to the risk of renal stone formation (Sibonga and Pietrzyk, 2017). The report also alludes to task analysis and task design, which were the topics of a separate evidence report (Sandor et al., 2013).
Although radiation both weakens bones that are in the radiation field and can impair healing, the threshold for such clinical impairment (approximately 20 gray [Gy] in clinical medicine) appears unlikely to be achieved during likely mission scenarios (Engleman et al., 2006).
Fracture management during a mission clearly interfaces with the “Medical Care” report (Antonsen et al., 2017). That report accurately identified fractures as a major concern for management during a mission. The lack of information concerning the best ways to manage a fracture during a mission needs to be addressed in greater detail in some part of the evidence reports.
To that goal, the committee recommends that the Fracture Report be expanded to include the risk and the management of fractures with an emphasis on fracture management during space missions. It would then
naturally include more evidence about management of osteoporotic fractures and a discussion about the management of fractures in microgravity (e.g., the possible use of pharmacologic agents or other adjuncts to fracture healing).
What Is the Overall Readability and Quality?
The report is well written, readable, and benefits from the expertise of the authors.
Is the Breadth of the Cited Literature Sufficient?
The evidence report goes into depth on many of the relevant studies, including bed-rest studies, and has an extensive bibliography. In the next update of this evidence report references could be added from the terrestrial experience with the treatment of fractures in osteoporotic individuals (e.g., Molvik and Kahn, 2015; Hegde et al., 2016) or in those with metabolic bone diseases; in particular, the (largely experimental) literature on the use of anabolic agents to facilitate fracture healing (e.g., Aspenberg et al., 2010; Ominsky et al., 2011; Jin et al., 2015), and the assessment and management of fractures in spinal cord injury patients with quadriplegia or paraplegia (de Bruin et al., 2000; Zehnder et al., 2004; Coupaud et al., 2015; Grassner et al., 2017). References to the extensive literature on tail-suspended rodents could also be included.
Is the Expertise of the Authors Sufficient to Fully Cover the Scope of the Given Risk? Is Input from Additional Disciplines Needed?
As noted, the addition of individuals with expertise in orthopedic surgery and endocrinology (specifically bone metabolism and pharmacologic means to enhance healing when fractures occur) would strengthen the disciplinary expertise relevant to this topic.
Has the Evidence Report Addressed Previous Recommendations Made by the IOM in the 2008 Letter Report?
The addition of this and other evidence reports related to bone demineralization reflect the growing recognition that this issue is of significance. Because this risk was not pulled out as a separate chapter in the
