Gap Osteo 2: What is the incidence & prevalence of early onset osteoporosis or fragility fractures due to exposure to spaceflight.
Last Published:  07/30/21 01:05:31 PM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Open
Description

Present State:

Osteoporosis is a medical condition of the skeleton that is characterized by low bone mass and severe structural deterioration which increases the probability of a fragility fracture (i.e., fracture due to minimal or no trauma). The hip and the spine are common skeletal sites for fragility fractures due to age-related declines in bone strength. According to a panel of osteoporosis experts (Bone Summit) and the Institute of Medicine (IOM) review of the Human Research Program (HRP) Evidence Book, there is enough indirect evidence to suggest that long-duration astronauts may develop premature osteoporosis. If conventional methods of risk assessment continue to be used, evidence for increased risk in the astronaut population may not be established because of the current inappropriately applied diagnostic guidelines, limitations of the Dual-energy X-ray absorptiometry (DXA) modality for bone assessments in astronauts, low subject numbers and time constraints (Bone Summit Report; Keyak, Bone, 2009). Even so, it would be prudent to monitor for the incidence of fragility fractures (traumatic fractures of hip or spine) during the lifetime of the astronaut. This epidemiological review (which quantifies a fracture outcome due to osteoporosis) is a conventional approach to confirm that osteoporosis or fragility fractures occur in greater number and/or at a younger age in the astronaut population than would be expected in the non-astronaut, terrestrial population. This epidemiological approach is greatly limited by low numbers of astronauts but it provides an important context for understanding the risk.

 

Interim Metrics (Sequential):

  1. Convene panel of clinical policy makers in osteoporosis for interim reviews of hip Quantitative Computed Tomography (QCT) surveillance data, bone-relevant data from Medical Requirements Integration Documents (MRIDs), and the epidemiological analysis of data from Lifetime Surveillance of Astronaut Health [LSAH] and Biomedical Data and Reduction Analysis [BDRA]. The interim reviews of data (“Bone Summit-like” meeting) will be conducted at intervals of 6 sets pre- post- and R+ 1 year of QCT study data until the end of the ISS platform availability to solicit the opinion of an expert panel (Level IV NASA Level of Evidence) regarding spaceflight as a risk factor for early onset osteoporosis. (75%)
  2. Conduct and provide report annually on epidemiology of premature osteoporosis in long-duration astronauts up to the end of ISS platform availability. (25%)
a.  Calculate odds or hazards ratio from LSAH database 
b.  Monitor risk using modified bone standards in long-duration astronauts (Gap Osteo
c.  Assess incidence of Fragility fractures, noting incidence at ages < 70 (males) or < 55 (females).
d.  Assess prevalence of atypical, low trauma fractures (other than hip, spine or wrist) in LSAH.

Approach:


Low number of subjects is a considerable limitation to generating an index of increased risk (as per non-advocate review (NAR) and Bone Summit panels). Given these constraints, gap closure could be determined by a clinical advisory panel acting as a Data Safety Monitoring Board (DSMB)-like board where the NASA levels of evidence are expert opinion (Level IV) and observational case series studies (Level III). The DSMB-like board shall rule when the incidence of fragility fractures is sufficient to indicate an increased risk for early onset osteoporosis in astronauts. This finding will establish the criticality of risk and the requirement for intervention type and timing (preflight, postflight, long-term health) for clinical practice guidelines. Moreover, the availability of Finite Element (FE)-based standards for hip strength (FE cut-point operating bands) will establish a non-permissible outcome cut-point that will take into account the expected decline in hip due to both aging and spaceflight. Hence, once FE-based standards are in place for selection and flight certification, an observed reduction in odds ratio might be expected. These QCT + FEM data would be collected until the end of the ISS six-month missions (2020) where, upon data review by the DSMB, clinical recommendations for longer-durations missions will be solicited.


Target for Closure
Evidence for increased risk in astronauts using conventional epidemiology (e.g., odds ratio), or evidence-based predictive modeling, compared to non-astronaut population. Ongoing review, reports repeated at yearly intervals, for Research and Clinical Advisory Panel (RCAP) decision regarding the "Level of Evidence" for substantiating risk.
Mappings
Risk Risk of Bone Fracture due to Spaceflight-induced Changes to Bone
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