I. SPECIFIC AIMS:
AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk.
AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.
II. SUMMARY OF WORK RELATED TO AIMS:
A. Overview of Year 2
During this second year of funding, NASA-JSC colleagues have been assembling the bone density datasets for all remaining US crewmembers and consenting the approximate 250 men and women in the US space program, who have had at least one bone density measured. At NASA-JSC, comprehensive risk factors known to be related to bone health are also being assembled and work is ongoing. At Mayo, data analyses for Aim 1 have been initiated with respect to the bone density data available on long-duration crewmembers. Fracture prediction models have also been developed using data on risk factors available in both US long-duration crewmembers and in the Mayo cohort. Initial data cleaning and exploratory work for Aim 2 has begun based on risk factor data available and shared to date, although complete datasets on risk factors (e.g., ,bone turnover markers, lean muscle mass, personal and family history of fractures, medication use, etc) are still being assembled.
B. Progress Related to AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. .
Informed consent has been achieved in all 32 US crewmembers (26 men, 7 women; age range: 37-54 years) who have flown on at least one long-duration space mission (100% participation rate).
To date, we have obtained informed consent on 123 (53%) of the 232 remaining US crewmembers (21/36 women and 102/196 men) who have had at least one bone density measurement available. The consenting process is ongoing. 3 have declined and 3 are lost to follow-up.
Bone density datasets for all long-duration crewmembers have been assembled and cleaned. Bone density datasets for the remaining US crewmembers are still being assembled at NASA-JSC. We anticipate that NASA-JSC colleagues will have consenting status complete and bone density datasets assembled and ready to share with Mayo investigators, for those who have consented, by the end of the second year of funding.
i) Creation of a bone mineral density (BMD) prediction model using the Mayo cohort:
We have created age- and gender-expected prediction models for BMD derived from 348 men (age range at baseline: 22-90 years) and 351 women (range: 21-93 years) representing an age-stratified, random sample of the adult community population (Mayo Rochester Bone Health Study cohort) and who have had longitudinal BMD measurements at identical sites to the US crewmembers. We then applied the created prediction models to the NASA cohort of long-duration US crewmembers.
Based on our models, the BMD at all sites immediately post-flight in US crewmembers were all significantly lower than would be expected. We did observe a unique finding of greater than expected loss of BMD in some upper arm sites which raises the possibility of other risk factors contributing to bone loss during space flight unrelated to mechanical unloading, but is being further explored. There were also observed differences between men and women which warrant further exploration, and that will be addressed in analyses related to Aim 2.
Preliminary work also reveal that following 6-18 months post-flight, BMD at most sites in US long-duration crewmembers is becoming closer to the expected values. However, the hip BMD still is significantly lower than expected at 1 year post-flight.
ii) Creation of a fracture prediction model using the Mayo cohort:
Fracture prediction models were also created using the Mayo Rochester Bone Health Study cohort, separately for men and women who were at least age 35. Fracture predictions for 5 and 10 years following the BMD measurement were estimated for immediate pre-flight, immediate post-flight and ~1 year post-flight BMD. We are currently conducting further analyses towards improvement of these models before final interpretation.
C. Progress Related to AIM 2: To provide a summary of the current evidence available on potential risk factors for bone loss, recovery and fracture following long-duration space exploration.
Data assembly at NASA-JSC on risk factors known to be related to bone loss and fracture risk is ongoing. We will use these data to help better understand the variability in BMD loss and recovery, post-flight. Risk factor data include, but are not limited to, medication use, personal and family history of fractures, bone turnover markers, and surrogates of exercise status in-flight, such as changes in strength measures, VO2 max and lean muscle mass. Data assembly and cleaning is ongoing. Exploratory descriptive analyses are being conducted on data available. Observed differences between men and women in Aim 1 will also be explored further by examining the role of different risk factors on bone loss.