NOTE: Extended to 6/30/2016 per P. Baskin/HRP (Ed., 1/5/15)

NOTE: Extended to 12/30/2014, per M. Covington/ JSC HRP (Ed., 7/3/14)

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) screen for optimal bone health in an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards to supplement the existing BMD T-score-based standards:

1) Develop a dataset of FE hip strengths from human subjects, with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at University of Califormia Irvine (Keyak JH, et al. Clin Orthop Relat Res. 2005 Aug;(437):219-28).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include International Space Station (ISS) astronauts.

2) Determine FE strength cutoffs, from Specific Aim 1b, to be used as a decision-tool by Space & Clinical Operations Division for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to the Space Medicine Space & Clinical Operations Division and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

Specific Aims

1) Develop a dataset of FE hip strengths for subjects a) with ages covering the age range of the astronauts, and b) for which fractures outcome data have been collected. Completed. 12/03/13.

2) Review and evaluate dataset by FE Task Group members to suggest method(s) by which FE strength cutoffs from this dataset could be to supplement current areal BMD-based standards for the following:

a) a non-permissible outcome (POL) for hip bone strength after spaceflight to establish level of countermeasure efficacy,

b) an additional metric for screening bone health in applicants to the astronaut corps who fail to meet the bone medical standard of hip T-score>-1.0,

c) a fitness-for-flight standard in astronauts for a second long-duration mission, and

d) an index for assessing an astronaut’s risk for overloading the hip due to certain post-mission physical activities.

3) A manuscript of FE Task Group opinions (#2 above) will be prepared for concurrence by Task Group members and submitted for publication. Hip “Load Capacity” as Cut-points for Astronaut Skeletal Health: Recommendations of the NASA Finite Element (FE) Strength Task Group. Andrew S. Michalski , Shreyasee Amin MD , Angela M. Cheung MD , Dianna D. Cody PhD , Joyce H. Keyak PhD , Thomas F. Lang PhD , Daniel P. Nicolella PhD , Eric S. Orwoll MD , Steven K. Boyd PhD , Jean D. Sibonga PhD. Completed. 9/30/18 and manuscript awaiting approval for submission to npgMicrogravity.

NOTE: Extended to 12/30/2014, per M. Covington/ JSC HRP (Ed., 7/3/14)

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) screen for optimal bone health in an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards to supplement the existing BMD T-score-based standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs, from Specific Aim 1b, to be used as a decision-tool by Space & Clinical Operations Division for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to the Space Medicine Space & Clinical Operations Division and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

1) Develop a dataset of FE hip strengths, of human subjects, that have all been generated by the same FE model; human subjects span ages of the astronauts population and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study provided QCT scans from 408 persons to Dr. Joyce Keyak who generated FE models from QCT data and estimated hip bone strength by FF model analysis that was developed at University of California at Irvine- UCI (Keyak, 2005). The contract with UCI was set up in June 2012 and this work was completed in December 2013.

b. FE data from 1a (above) were combined with FE data generated from other applications of Keyak FEM to QCT scans of cohorts from University of California at San Francisco -UCSF studies, which also included 13 ISS astronauts. The full FE Strength database is expected to be delivered in May 2014 following data cleaning.

2) FE strength cutoffs to be used for decision-making by Space & Clinical Operations Division will be determined, if feasible, by the using conventional biostatistical approaches (receiver operating characteristic [ROC] and Area Under the Curve), in order to determine the following decision points (below, a-d) –

a. Screening an applicant for astronaut candidacy

b. Qualifying an astronaut for a long-duration (LD) mission

c. Qualifying a previously-flown LD astronaut for a second LD mission

d. Understanding a causality for a post-mission fracture or osteoporosis diagnosis.

3) The generated FE strength cutoffs will be presented to FE Task Group II (with inclusion of a physician, FE modeler and cohort biostatisticians from UCSF, Mayo, and JSC) for review and possible refinement. The final FE strength cutoffs will be recommended to Human Health Countermeasures to process through Transition-to-Operations [TTO].

NOTE: End date is 9/30/2014 per PI (Ed., 4/24/14)

NOTE: Gap changes per IRP Rev E (Ed., 1/27/14)

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) qualify an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs from to be used as a decision-tool by Space Medicine for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to Space Medicine and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)

a. The Rochester Bone Health Study will provide QCT scans from 408 persons to Dr. Joyce Keyak who will estimate hip bone strength using her developed FEM at UCI (Keyak, 2005). The contract with UCI was set up in June 2012 and this work is in progress.

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans of cohorts from UCSF studies, which include ISS astronauts. The full FE Strength database is expected to be complete in November 2013.

2) Determine FE strength cutoffs to be used for decision-making by Space Medicine for the following scheduled decision points (below, a-d) – using conventional biostatistical approaches (receiver operating characteristic [ROC] and area under the curve [AUC]) to be performed by NASA/JSC Biostatisticians and working with representatives of Space and Clinical Operations [SD]:

a. Qualifying an applicant for astronaut candidacy

b. Qualifying an astronaut for a long-duration (LD) mission

c. Qualifying a previously-flown LD astronaut for a second LD mission

d. Assuming responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present generated FE strength cutoffs to FE Task Group (with inclusion of cohort biostatisticians from UCSF, Mayo, and JSC) for review and possible modification. Recommend finalized FE strength cutoffs to Human Health Countermeasures to process through Transition-to-Operations [TTO].

Specific Aims

NASA’s Bone medical standards establish the “operating bands for bone health” that: a) qualify an astronaut for long duration spaceflights, b) establish the non-permissible outcome for a spaceflight mission, c) provide a level of efficacy for countermeasures as well as d) qualify an applicant for the astronaut corps. The current Bone medical standards are based upon the diagnostic criteria for a terrestrial population known to be at risk for osteoporosis, i.e., perimenopausal and postmenopausal women and men over the age of 50.

As a follow-up to the Bone Summit RCAP recommendation, the FE Task Group proposes the following Specific Aims to accomplish the task of generating of FE-based medical standards:

1) Develop a dataset of FE hip strengths from human subjects: with ages covering the age range of the astronauts and for which fracture outcome data have been collected.

a. The Rochester Bone Health Study (as authorized by Drs. Sundeep Khosla and Shreyasee Amin) will provide QCT scans from ~408 persons to Dr. Joyce Keyak who will develop FE models and estimate hip bone strength using the FE modeling developed at UCI (Keyak, 2005).

b. FE data from 1a (above) will be combined with FE data generated from other applications of Keyak FEM to QCT scans from additional study cohorts, which include ISS astronauts.

2) Determine FE strength cutoffs from to be used as a decision-tool by Space Medicine for the following scheduled decision points (a-d):

a. to qualify a sub-set of applicants for astronaut candidacy (those who currently are not qualified due to hip T-score between -1 and -1.5) for further medical testing

b. to qualify an astronaut for a long-duration (LD) mission

c. to qualify a veteran LD astronaut for a second LD mission

d. to establish responsibility by occupational space medicine for a post-mission fracture or osteoporosis diagnosis.

3) Present, review, and finalize the generated FE strength cutoffs with FE Task Group (along with the inclusion of cohort biostatisticians) to recommend to Human Health Countermeasures as a deliverable to Space Medicine and Office of Chief Health and Medical Officer.

(Ed. note: revised version, per PI. 8/27/2013)