Musculoskeletal changes during long duration spaceflight · 2019. 7. 30. · Jess Snedeker MS PSU 2000 Tom Lang UCSF Jean L. McCrory PhD 1997/Post Doc 1998 Gail Perusek ... 7. Ferguson

Musculoskeletal changes during long duration

spaceflight

Orthopaedics

UW

Peter R. Cavanagh

DISCLOSURES

Peter Cavanagh has received grants from NASA and the National Space Biomedical Research Institute.

He is a member of the Standing Review Board for the Space Shuttle and the International Space Station Program.

©2011 Peter R. Cavanagh

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Locomotion

Featured Science

Brian DavisPhD PSU 1990

Kerim GencMS PSU 2003

MS CWRU 2009PhD CWRU 2011

Andrea HansenPost-doc

UW 2009-11

Rodger KramMS PSU 1986

Exercise equipment Bone Loading Remote Monitoring


Our First Venture into Space Studies

ACSMs Virtual Museum


Hip-Knee Angle-Angle diagrams

STS-7 and STS-8 (1983) Thornton et al. 1997


Outline

MUSCLEAlterations with SpaceflightMechanismsCountermeasures

BONEAlterations with SpaceflightMechanismsCountermeasures

Future of Life Science Research in Space


What is Long-duration?

842

187

438

18141

199

900

0

200

400

600

800

1000

1960 1980 2000 2020 2040

Du

rati

on

in D

ays

YEAR

Mission Durations

Skylab 4ISSExp 1 – Exp 20

ShuttleSTS1 – STS 80

MirMir EO1 – LD2

Mars


Time Accumulated by Repeat Fliers

0

200

400

600

800

1000803 769 747

678 651585 555 553 541 514

6 5 3 2 5 3 4 4 2 4 Number of Flights

Life

tim

e d

ays

in S

pac

e

Peggy Whitson #20 376.7 daysMichael Fincke #26 365.9 days


MUSCLE: Alterations with Spaceflight

•Fitts RH, Trappe SW, Costill DL, Gallagher PM, Creer AC, Colloton PA, Peters JR, Romatowski JG, Bain JL, Riley DA. Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres. J Physiol. 2010 Sep 15;588(Pt 18):3

Fitts RH, Trappe SW, Costill DL, Gallagher PM, Creer AC, Colloton PA, Peters JR, Romatowski JG, Bain JL, Riley DA. Prolonged space flight-induced alterations in the structure and function of human skeletal

muscle fibres. J Physiol. 2010 Sep 15;588(Pt 18):3567-92.

Trappe S, Costill D, Gallagher P, Creer A, Peters JR, Evans H, Riley DA, Fitts RH. Exercise in space: human skeletal muscle after 6 months aboard

the International Space Station. J Appl Physiol. 2009 Apr;106(4):1159-68. Epub 2009 Jan 15. PMID: 19150852

Adams GR, Caiozzo VJ, Baldwin KM. Skeletal muscle unweighting: spaceflight and ground-based models. J Appl Physiol. 2003 Dec;95(6):2185-201. Review. PMID 14600160


MUSCLE : Mechanisms for Alterations

• Fiber Type: Type 1 > loss/conversion

• Fiber Type: Type 2 more preserved

• Change in protein synthesis

• Activation of ubiquitin-dependent proteolyticpathway (Ikemoto et al. 2001)

• Impaired ability to replace or repair degraded contractile proteins (Kortebein et al. 2007).


MUSCLE : Countermeasures

Flywheel

Exercise equipment

ARED

iRED


MUSCLE : Phamacological Countermeasures

Myostatin inhibition

Virginia Ferguson, Rachel Paietta, Louis Stodieck, Andrea M. Hanson, Mary H. Young, Ted Bateman, Michael Lemus,Paul Kostenuik, Eric Jiao,•Xiaolan Zhou, Jin Lin Wang, John Lu, Yanping Song, Keith S. Kwak, Qingsheng Jiao, Robert Rosenfeld, Qing Chen, Thomas Boone, W. Scott Simonet, David L. Lacey, Alfred L. Goldberg and H.Q. Han,Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB Anta

Zhou et al. 2010 Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB Antagonism Leads to Prolonged Survival.

http://www.asbmr.org/http://www.cell.com/issue?pii=S0092-8674(10)X0017-4


BONE and MUSCLE INTERACTION

Ferguson et al. Inhibiting myostatin prevents microgravity-associated bone loss in mice. J Bone Miner Res 24 (Suppl 1).

Warner SE, Sanford DA, Becker BA, Bain SD, Srinivasan S, Gross TS. Botox induced muscle paralysis rapidly degrades bone. Bone. 2006 Feb;38(2):257-64.


Short Arm Centrifuges

NASA/Wyle Centrifuge ESA/QinetiQ Centrifug(ergometers, vibration plates, and “jojo” inertia wheels)

MIT Rotator


Space Cycle

Yang, Caiozzo et al. 2007


Space Cycle with Shark Cage

Simulink Model


Without appropriate countermeasures, spaceflight of 2 years or longer will present serious risks due to progressive bone fragility

Recapturing SpaceThe National Academies 2011


BONE : 3 Studies - Methodology

(LeBlanc et al. 2000) (Lang et al. 2004)Rambaut and Johnston (1979)

Single Photon Absorptiometry Dual Photon Absorptiometry Quantitative Computed Tomography


BONE: BMD changes in Skylab 4

Single Photon Absorptiometry

% B

MD

Lo

ss p

er M

on

th

Rambaut and Johnston (1979)


BONE: BMD changes in Mir flights

LeBlanc et al. 1996 Dual Photon Absorptiometry (DXA)

% B

MD

Lo

ss p

er M

on

th


BONE: BMD changes in ISS Missions

Lang et al. 2004

-3

-2.5

-2

-1.5

-1

-0.5

0

Fem

ora

l Nec

k C

ort

ical

Fem

ora

l Nec

k Tr

abe

cula

r

Tro

chan

ter

Co

rtic

al

Tro

chan

ter

Trab

ecu

lar

Spin

e Tr

abe

cula

r

Spin

e p

ost

erio

r

% B

MD

Lo

ss p

er M

on

th

Quantitative Computed Tomography


BONE: Changes in Strength

Keyak et al. 2004 FEM and Quantitative Computed Tomography

Strength in stance loading decreased at mean rates of 2.6% (0.6% to 5.0%) per month

Strength in fall loading decreased at 2.0% (0.6% to 3.9%) per month

Stance strength decrease ~ 2x BMD decrease


BONE: Summary

Post MenopausalWoman on earth

Male Astronauton Space Station

-0.15% -0.8% -1.4%

BMD/Month


BONE : No Progress in a Decade

-1.2%

per mo

-1.4%

per mo

n=18 Lang et al. 2004n=16 LeBlanc et al. 1996

Post menopausal

women

0.15% per mo

Mir ISS


BONE : Recovery after Spaceflight

Mir: 28 male, 1 femaleISS: 15 male, 2 female

Sibonga et al. 2007


BONE : 50% Recovery Time

0

100

200

300

DA

YS


BONE: Structural Change at 1 Year

Lang et al. 2006

D

Bending strength proportional to moment of inertia: Iyy = p(D4 – d4)/64

+15%

d -50%

Iyy unchanged

• Bone mass > 8.1% (from -11%)• vBMD in femoral neck >0.9% • Bone volume >7.2%

Similar to age-related changes observed by Riggs et al. 2004


Bone: Mechanisms


Bone Remodeling

Courtesy of MSD


32Smith et al. (1998)

Bone: Re-analysis of Skylab Samples

Marker of resorption


33

Bone: Rodents mechanisms may differ

Wronski and Morey 1983

An inhibition of periosteal bone formation occurred during spaceflight in the tibial and humeral diaphyses (of rats).


BONE: The Mechanostat: Frost 1987

Strain-based model

100-300ms 1500-3000ms

Bone Loss

Bone Gain

LOADING REPETITIONS


BONE: Loading

Houston

8.5 Hrs

ISS

9.6 Hrs


BONE : Exercise CountermeasuresPeak loading during cycling, walking and running

0g

1g

CyclingWalking

Running

0.0

0.5

1.0

1.5

2.0

2.5

Peak F

orc

e (

Bo

dy W

eig

ht)

Peak loads during running in Zero g were approximately 60% of 1g values


Countermeasures: External Loading


http://www.nasa.gov/audience/foreducators/teachingfromspace/dayinthelife/exercise-adil-index.html

"Each Station crew member is scheduledfor an hour of cardio and an hour of resistive exercise each day while we are on orbit"

Countermeasures: Duration of Loading


135-150 min. of “scheduled” exercise time

Short Term Plan: STP

Countermeasures: Duration of Loading


Load Monitoring: Exercise Duration


Activity Monitoring: Actual Loading Duration


Activity Monitoring: Actual Loading Duration

Assigned Exercise Time = 146.8 ± 6.28 minTotal Loaded Time = 43.11 ± 15.0 minMean Exercise Efficiency = 29.4%


Exercise Countermeasures: The Bolus Assumption

ISS

Earth

1BW

1BW


Accumulating Daily Load

Exercise CMIVAEVA

Required Dose of Loading (Daily Loading Stimulus DLS) for Optimal Bone Health


BONE : The use of osteoprotective drugsBisphosphonates

• LeBlanc et al. 2002 Bedrest. Alendronate attenuated bone loss in 8 male subjects during 17 weeks of horizontal bedrest.

• LeBlanc et al. ISS on-orbit experiment in progress

• Risk of Bisphosphonates in young individuals


BONE : The use of osteoprotective drugsNew Drugs

Denosumab FDA approved June 2010, under the trade name Prolia. Human monoclonal antibody inhibits RANK-L

Sclerostin gene deletion increased bone formation and bone strength in mice and prevented loss during tail suspension. Li et al 2008, Lin et al. 2009


The Future

Decadal Survey http://www.nap.edu/catalog/13048.html

April 2011


Key Recommendations

For the past decade, the emphasis of biological research has been on human countermeasures.

The panel is unanimous in its recommendation that an animal habitat should be incorporated as soon as possible into the ISS

CHANGE OF FOCUS


Key Recommendations

Implementation of decadal research objectivities will have sufficient governmental priority between 2010-2020 to supersede existing NASA operational plans.

USE OF THE NATIONAL LABORATORY


Key Recommendations

• Implement the Safe Passage report recommendations

• Much remains to be done in regard to providing more widespread access to data on astronaut health

BETTER ACCESS TO ASTRONAUT HEALTH DATA


Acknowledgements

COLLEAGUES COLLABORATORS

Jess Snedeker MS PSU 2000 Tom Lang UCSF

Jean L. McCrory PhD 1997/Post Doc 1998 Gail Perusek NASA GRC

Ruth Ochia PhD Post Doc 2000 Kelly Gilkey NASA GRC

Andrea Rice Cleveland Clinic 2003-date Marsha Nall NASA GRC

Sara Novotny Cleveland Clinic 2005-date Stuart Lee NASA JSC

Raghavan Gopalakrishnan CCF 2005-2008 Tim Streeper UCSF

Ricky Englehaupt Cleveland Clinic 2005-2008 Christian Maender NASA JSC

Matthew Kuklis Cleveland Clinic 2005-2008 Brad Humphreys NASA GRC

Angelo Licata Cleveland Clinic 2005-2008 Vince Caiozzo UCI

Hakan Ilaslan Cleveland Clinic 2005-2008

Kerim Genc PSU CCF UW 2001-2011 FINANCIAL SUPPORT

Brian Davis PSU CCF 1988-2008

Andrea Hanson CCF 2009-2001

Thank You

Orthopaedics

UW

[email protected]

http://bit.ly/ksbQl

Download presentation from:

References for Cavanagh ACSM Lecture 2011

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3. Adams, G.R., Haddad, F., and Baldwin, K.M. 2003. Gravity plays an important role in muscle development and the differentiation of contractile protein phenotype. Pp. 111-122 in The Neurolab Mission: Neuroscience Research in Space (J.C. Buckley and J.L. Homack, eds.). NASA SP 2003-535

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7. Ferguson V, Paietta R, Stodieck L, Hanson AM, Mary H. Young MH, Bateman T, Lemus M, Kostenuik P, Jiao E,Zhou X, Lu J, Simonet W, Lacey D, Han HQ. 2009 Inhibiting myostatin prevents microgravity-associated bone loss in mice. J Bone Miner Res 24 (Suppl 1). Available at http://www.asbmr.org . Accessed 06/02/2011.

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Musculoskeletal changes during long duration spaceflight · 2019. 7. 30. · Jess Snedeker MS PSU 2000 Tom Lang UCSF Jean L. McCrory PhD 1997/Post Doc 1998 Gail Perusek ... 7. Ferguson