Initial/Present State:
As reported by Cooper and Melton
(1992), age-related fractures (i.e., fragility fractures due to osteoporosis)
occur in women in their 6th decade of age (50-59) for wrist and
spine and in their 7th decade (60-69) for hip. For men, there are
essentially no osteoporotic fractures of the wrist; fractures of the hip and
spine occur after age 70. After age 50, fractures in women are twice as
prevalent as in men, but the morbidity and mortality associated with fractures
in males is more severe than in women (Myers, Am J Epi 1991, Schurch JBMR 1996,
Forsen Osteoporosis Intl. 1999, Kiebzak Arch Int Med 2002). The goal of
osteoporosis therapy is to diagnose and treat the condition prior to fracture
and the probability of fracture drives the requirement for this intervention.
Younger persons (<50 years) however, are not considered at risk for fracture
(Kanis, Osteoporosis Int, 2001); in the absence of risk factors for, or
evidence of, osteoporotic fractures, a younger person with a T-score of <
-2.5 would not be treated. Likewise, the requirements for countermeasures
(i.e., exercise, dietary, pharmaceutical or combination thereof) to mitigate
premature osteoporosis in astronauts due to spaceflight should depend
upon fracture probability because the currently applied methods for assessing
skeletal integrity (i.e., aBMD T-scores) are not appropriate for the ages of
the active astronauts (only perimenopausal, postmenopausal woman and men >
50 years).
Hence, given the low fracture probability and shorter
mission durations on the International Space Station (ISS), the a panel of
clinical experts convened in 2010 (Orwoll et al, JBMR, 2013) recommended mitigating
bone loss risk factors (e.g., inadequate nutrition, reduced
weight-bearing activity) as the first approach for in-flight bone loss
interventions on the ISS. Pharmaceuticals should be reserved as Plan B or
for longer duration, exploration class missions. However, this “Bone Summit”
Panel also stated that mitigation approaches need to be re-evaluated (type,
method, timing, stringency) for different mission architectures and as
surveillance data accumulate for review. With an expanded dataset from
astronauts, the risk for osteoporosis could be better defined.
Prior to closure of Gap Osteo 1, the Bone Summit clinical
advisory panel had recommended a physiological trigger which could also serve as
an index for countermeasure efficacy. Specifically, effectiveness of a)
in-flight countermeasures would mitigate any decline in hip trabecular BMD; and
b) post-flight countermeasures spaceflight would restore hip trabecular BMD to
its preflight status (within measurement error) by R+2 years. This
physiological trigger was identified because declines in the BMDs of the hip trabecular
bone compartments are aBMD-independent predictors of fracture risk in elderly
males and females (Black et al. JBMR, 2008;Bousson et al, JBMR, 2011); the
failure for BMD to be restored to preflight status is suggestive of
irreversible changes to trabecular bone (Carpenter et al. Acta Astronautica,
2010).
Citations
(partial):
Black DM, Bouxsein ML, Marshall LM, Cummings SR,
Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES; Osteoporotic Fractures in
Men (Mr. OS) Research Group. Proximal
femoral structure and the prediction of hip fracture in men: a large
prospective study using QCT. J Bone Miner Res. 2008;23(8):1326–33.
Bousson
VD, Adams J, Engelke K, Aout M, Cohen-Solal M, Bergot C, Haguenauer D, Goldberg
D, Champion K, Aksouh R, Vicaut E, Laredo JD. In vivo discrimination of hip
fracture with quantitative computed tomography: results from the prospective
European Femur Fracture Study (EFFECT). J Bone Miner Res. 2011;26(4):881-893.
Carpenter
RD, LeBlanc AD, Evans H, Sibonga JD, Lang TF Long-term changes in the density
and structure of the human hip and spine after long-duration spaceflight. Acta
Astronautica. 2010;67:71–81.
Kanis JA, Johnell O, Oden A, Dawson
A, DeLaet C, Jonsson B. Ten year
probabilities of osteoporotic fractures according to BMD and diagnostic
thrseholds. Osteo Intl.
2001;12(12):989-95.
Orwoll ES, Adler RA, Amin S, Binkley
N, Lewiecki EM, Petak SM, Shapses SA, Sinaki M, Watts NB, Sibonga JD. Skeletal health in long-duration astronauts:
nature, assessment, and management recommendation sfron the NASA Bone Summit J
Bone Miner Res. 2013:38(6):1243-55.
Interim Stages/Metrics (Sequential):
- Convene
Research and Clinical Advisory Panel (RCAP) on a triennial basis to
evaluate available surveillance data from Osteo 2, Osteo 3, Osteo 4,
Osteo 5 and Osteo 6 and data acquired
from Hip Quantitative Computed Tomography (QCT) Study (pre-, post-, R+1
year and R +2 years, if required). (80%)
- RCAP
formulates Clinical Practice Guidelines (CPGs) for a recommended
mitigation approach (specifying type and timing of mitigation) for
early onset osteoporosis (fracture during long-term health [LTH]). (15%)
- Submit
recommended CPGs (#2) to Human
Health Countermeasures Element for processing through Transition-to-Operations.
(5%)
Approach:
Access countermeasure evaluations from Nutrition,
Pharmacology and Exercise Disciplines to address (singly or in combination) the
following queries, i.e., does countermeasure protect against bone loss in the
trabecular hip BMD?; does the countermeasure prevent the decline in hip FE bone
strength above the minimum permissible FE bone strength.? Design clinical
validation of best suite of countermeasures in a flight experiment based upon
previous queries.
As an alternative index for countermeasure efficacy, the optimal combination of
countermeasures should be able to mitigate the decline in the hip trabecular
BMD or restore it to preflight status. This site is an independent predictor of
fracture risk in elderly humans; the lack of recovery at this site is
suggestive of irreversible changes. Other conventional QCT hip parameters
are also predictive of hip fracture (although persistent declines were not
detected in astronauts) and may be included in surveillance. This index of
countermeasure efficacy is also generated as per Osteo 3.
No Documentation Available