Skeletal Consequences of Spaceflight Thanks to Dr. Grant Schaffner Prof. Dava Newman Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 2 Bone - Summary Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 3 Skeletal Consequences of Spaceflight Background ò Early flights: very little idea of physiological changes to expect big concerns: respiration, cardiovascular bone probably wasn t a serious consideration ò What has been learned in the pa st 37 years of human spaceflight ? Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 4 Spaceflight Bone Loss in Humans F l i ght / S t ud y Fi n d i n g R ef er en ces G e m i ni 4 , 5 , a nd 7 4- 14 da y s ; C al c a neus and m et ac ar pal bone dens i t y l os s es o f 2- 4% f or 5 as t r on aut s , a nd 9% f or s i x t h V os e , 1 974 So y u z 9 18 day s ; 8- 1 0% dec r eas e i n c al c a neus d ens i t y f or bot h c os m ona ut s B i r y k ov and K r as ny k h , 1970 Ap o l l o 1 7 12. 6 day s ; m ean C a l o s s of 0 . 2% of t ot al body and m ean P hos phor us l os s of 0. 7% of t ot a l b ody t hr ou gh i nc r eas e d ur i n ar y and f ec al ex c r et i on R a m ba ut , et al . , 19 75 S ky l ab 2 M i ssi o n N o s i gni f i c ant bo ne m i ner a l c ont ent c h anges i n ar m ; c al c a neus l os s r e t ur ned t o nor m a l b y 87t h day pos t f l . V oge l & W hi t t l e, 1976 Long Te r m F ol l ow - U p of S k y l a b B one D e m i n. S t a t i s t i ca ll y s i g n if ic a n t lo s s o f o s ca lc i s m i n e r a l in ni n e S k y l ab c r ew m em ber s , 5 y ear s af t er f l i ght T i l t on, et al . , 1980 C o m b in e d U.S . / U.S . S . R . S t udy of Long Te r m Fl i g h t QC T o f s p i n e ; U p t o 8 m o n t h s ; N o l o s s i n v e r te b r a l bodi es , but 8% l os s i n pos t er i or el em ent s ( 4% l os s i n v ol um e of at t ac hed m us c l es ) ; ex er c i s e c ount er m eas ur es onl y par t i al l y s u c c e s s f ul O g anov , et al . , 1990 M i r 366- D ay M i ssi o n O ne c os m onaut a v er aged 10% l os s of t r abec u l ar bone f r om L1 , L2, L3; m eas ur ed by Q C T G r i gor i ev , et al . , 1991 M i r 4 . 5 - 6 M ont h F l i ght s Q D R as s es s m ent of B M D ; t ot al body m i ner al l os s e s av er aged 0. 4% ; m os t m ar k e d l oc al l os s w as i n f e m o r a l n e c k a n d gr e a t e r t r oc ha nt e r - - up t o 1 4 % O g anov , et al . , 1992 M i r 1 a nd 6 M ont h F l i ght s pQ C T ; not i c eabl e l os s of t r abec u l ar an d c or t i c al bone i n t i bi a af t er 6 m ont hs C o l l et , et al . , 199 7 NAS DA S t u d y o f 2 NA S A A s t r ona ut s 42 y . o. f e m al e and 32 y . o. m al e; s hor t f l i gh t ; negat i v e c al c i um bal anc e; 3. 0% l os s of B M D i n L2 - 4 M i y a m o to , e t a l ., 1 9 9 8 Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 5 Spaceflight Bone Loss in Animals F l i ght / S t ud y Fi n d i n g R ef er en ces C o sm o s 605 R at s ; B on e f or m at i on r educ ed i n m e t aphy s es of l ong bones Y ago dov s k y , e t a l . , 1976 C o sm o s 782 R at s ; 40% r educ t i o n i n l engt h of pr i m ar y s p ongi os a due t o r e duc ed f or m a t i on an d i nc r ea s ed r es or pt i on A s l i ng, 1 978 C o sm o s 782? R at s ; O s t eobl as t di f f er e nt i at i on i n non- w ei g ht - b ear i n g si t e s uppr es s ed dur i ng w ei ght l es s ne s s R o ber t s , 1981 C o sm o s 936 R at s ; 30% d ec r ea s e i n f em or al br ea k i ng s t r engt h o f f em or a w i t h r ec ov er y of no r m al pr oper t i es af t er 25d S pe c t or , et al . , 1983 C o sm o s 782 & 9 36 R at s ; A r r e s t l i ne s e par a t i n g bon e f or m ed dur i ng and pos t - s p ac ef l i ght ; def ec t i v e and hy pom i ne r al i z ed bone T ur ner , et al . , 1985 R at T ai l S u sp en si o n , 1984 U p t o 15 day s ; C al c i um c ont e nt : t i bi a = 86. 2 + / - 2. 5 % , v er t ebr a = 75. 5 + / - 3. 5% of c ont r o l G l obus , e t a l . , 1984 C o sm o s 1514 P r i m at es ; 5 d ay s ; r es o r pt i on i nc r eas ed du r i ng f l i ght C a nn, et al . , 1986 C o sm o s 1667, 188 7, 2044 P r i m at es ; 13 day s ; l ow er m i ner al i z at i on r a t e and l es s bone m i ner al i z ed; l ongi t udi nal gr ow t h s l ow ed C a nn, et al . , 1990 C o sm o s 1667 R at s ; 7d s pac ef l i ght v s 7d t a i l - s us pens i o n; l os s of t r abec ul ar bon e i n pr ox t i bi al m et a ph m or e ex t ens i v e in f l ig h t r a t s V i c o, et al . , 1991 C o sm o s 2044 R at s ; F r ac t ur e r ep ai r pr oc es s i m pai r ed du r i ng f l i ght K ap l ans k y , et al . , 199 1 C o sm o s 2229 P r i m at es ; 11. 5 day s ; t endenc y t ow ar d dec r eas ed B M C dur i ng f l i ght ; onl y par t i al r ec o v ey 1 m ont h a f t e r Z er at h, et al . , 1996 R at T ai l S u sp en si o n , 1998 U nl oaded bones di s pl a y r e duc ed os t eob l as t nu m be r , gr ow t h, and m i ner al i z at i on r at e i n t r a bec ul a r bone M o r ey - H ol t on and G l obus , 1 998 Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 6 Bedrest / Hypokinesia Studies Models for Weightlessness of Spaceflight S t udy F i nding Re f e r e n c e s 5- 36 W eek s B ed r est 90 healt h y y oung m en ; 5% los s of c a lc aneal m i ner la eac h m o nt h; m ec han ic al and bioc hem i c al c ount er m eas ur es no t s uc c es s f ul S c hneider and M c Donald, 198 4 120- d ay B e d r est M i ner aliz at ion r a t e s l o wed; c o nt r a dic t or y r e s u lt s dem ons t r at e dif f ic ult i es of bedr es t as s pac e a nalog V i c o, et al. , 198 7 17- w eek B e d r est 6 healt hy y oung m ale s ; 6 m ont hs of r eam bula t ion; B M D % c h an g e ( p < . 05) : f emo ra l n eck ( F N) - 3. 6, tr o c h a n t e r (T ) -4 . 6 ; % / w e e k (p < . 0 5 ): F N -. 2 1 +/ - . 0 5 , T - . 27 + / - . 05; Reamb u l at i o n % re co very: F N 0 . 00 + / - . 0 6 , T 0 . 0 5 +/ - . 0 5 (p r o x . fe m u r d i d n o t r e c o v e r w e l l ) Le B l anc , et al. , 1990 3 7 0 -d a y A n ti o r th o s ta ti c Hyp o k i n e s i a T e s t Highes t los s es in f oo t bones ; r em edial m eas u r es delay os t e opor os is b u t do not c o m p let e ly ex c l u d e it ; r es u lt s o bt ained by d i f f er ent m et h ods of t en c on f lic t ing Z a ic hic k and M o r u k o v , 19 98 Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 7 Summary of Findings ò Significant bone loss in weightlessness ò Calcium excretion increases negative balance ò Bone mineral density decreases weight bearing areas: 1-2% per month ò Osteoblast (builders) proliferation and activity reduced, while osteoclasts (consumers) appear to be unaffected ò Fracture repair may be impaired ò Bone strength is reduced Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 8 Research Questions ò What is the rate of bone loss in critical areas? ò How does this affect bon e strength? ò What is the risk of fracture? duration of spaceflight activity, gravity level bone habitus : body weight, etc. ò What countermeasures are possible and how effective are they? Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 9 Current Research Justification ò Focus on critical weight bearing areas and regions of rapid bone loss (related du e to remodeling) lumbar spine proximal femur (hip) ò Presently, bone strength estimated from DXA BMD (or BMC) correlation with failure load Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 10 Current Research 6000 5000 Failure Load (N) 4000 3000 2000 r 2 = .71 y = 4,524x + 470 p < .001 1000 0 0 0.2 0.4 0.6 0.8 1 Neck BMD (gm/cm 2 ) ò Neglects: specific loading condition, body habitus , bone geometry, 3-D density distribution (DXA is 2-D) ò Does not exploit engineering theory Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 11 Other Research Efforts Curved Beam Model from DXA (Beck & Ruff, 1996) ò Use algorithm to get section properties (A, I) from DXA scan ò Develop curved beam model with stress concentration due to curvature ò Apply loads and assess stress on medial and lateral edges to determine failure load ò Limitations: 2-D, beam theo r y Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 12 Finite Element Analysis Approach Collaboration with Orthopaedic Biomechanics Lab (Oden & Selvitell i ) QCT scans and Stack NIH Image Extract contours contours to define geometry 3-D Finite Element Model Extract density distribution (trabecular area) Define elemen t material prope rties Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 13 QCT Slice Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 14 Skeletal Representations Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 15 Meshing ò Cut selected contours into subsect ions to guide meshing so that warped elements are avoided and mesh pattern aligns with density distribution ò Quadrilateral elements with 27 nodes per e lement Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 16 Assign Element Material Properties ò Use empirical modulus relationships to assign values based on density ò Human trabecular and cortical bone assumed to be transversely isotropic assign elastic constants for each elem ent: E, E , ν , ν , G, G . Poisson s ratio assumed constant ( ν = ν = 0.3). Source: Selvi tell i , 1997 Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 17 Apply Boundary Conditions ò Loads joint contact muscle forces? ò Constraints Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 18 Convergence Study 231 Elem . 1,344 Elem . 4,960 Elem . 2,625 Elem . Convergence Study - Average Displacement 0.134 0.1336 Displacement (mm) 0.1332 0.1328 0.1324 0.132 0 1000 2000 3000 4000 5000 Number of Elements Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 19 Failure Analysis Algorithm No Yes Update e, s FE Model Increment Displ acement Calcul ate Strains and Reacti o n Forces Calcul ate e ma x (prin ) Reduce Modul us End Element Fail ure? Model Fail ure? Yes No ABAQUS User Subroutine Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 20 Preliminary Results Astronaut Skeletal Modeling I Dynamic Model of Fall on Hip II Structural Analysis of Femur