Last Published:  03/26/21 03:33:57 PM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Open
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):

  1. 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%)
  2. 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%)
  3. Submit recommended CPGs (#2) to Human Health Countermeasures Element for processing through Transition-to-Operations. (5%)

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.

Target for Closure
Identified set of optimal countermeasures, with formulated set of Clinical Practice Guidelines (CPGs), to be implemented (and at which phase, pre-flight, in-flight and postflight) to maintain astronaut bone strength above “red zone” identified in Gap Osteo 1.
Risk Risk of Bone Fracture due to Spaceflight-induced Changes to Bone
You are here! Gap Osteo 7: We need to identify options for mitigating early onset osteoporosis before, during and after spaceflight.

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