Space Biomedical Engineering Life Support Space Biomedical Engineering Life Support Skeletal Consequences of spaceflight Thanks to dr grant schaffner Prof dava newman
Skeletal Consequences of Spaceflight Thanks to Dr. Grant Schaffner Prof. Dava Newman
Prof Dava Newman 16. 423J/HST5 15J Space Biomedical Engineering and Life Support Bone -Summary RaulFs NHANE S loading Absent eomEr STH stres stren ulfilas Spa ce exercise loAds ocal bU mod&lin remodeling decreased load
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 Early flights: very little idea of physiological changes to expect -big concerns: respiration, cardiovascular -bone probably wasn't a serious consideration What has been learned in the past 37 years of human spaceflight?
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 œ big concerns: respiration, cardiovascular œ bone probably wasn‘t a serious consideration ò What has been learned in the past 37 years of human spaceflight?
Prof dava newman 16.423J/HST515J Space Biomedical Engineering and Life Support Spaceflight Bone Loss in Humans Flight /Study Finding References Gemini 4. 5 and 7 4-14 days; Calcaneus and metacarpal bone density Vose, 1974 losses of 2-4% for 5 astronauts and 9% for sixth Soyuz 9 18 days; 8-10% decrease in calcaneus density for Birykov and Krasnykh both cosmonauts 1970 Apollo 17 12.6 days; mean Ca loss of 0. 2% of total body and Rambaut,et al, 1975 mean Phos phorus loss of 0.7% of total body through increased urinary and fecal excretion Skylab 2 Mission No significant bone mineral content changes in arm; Vogel& Whittle, 1976 calcaneus loss returned to normal by 87 th day postil Long Term Follow-Up of Statistically significant loss of os calcis mineral in Tilton, et al., 1980 Skylab Bone Demin nine Skylab crewmembers, 5 years after flight Combined U.S. /U.S.S.R. QCT of spine; Up to 8 months; No loss in vertebral Oganov, et al., 1990 Study of Long Term bodies, but 8% loss in posterior elements(4% loss in Flight volume of attached muscles ) exerci countermeasures only partially successful Mir 366-Day Mission One cosmonaut averaged 10% loss of trabecular Grigoriev, et al, 1991 from L1, L2, L3; measured by QCT ir 4.56 Month Flights QDR assessment of BMD; total body mineral losses Oganov, et al., 1992 averaged 0. 4%; most marked local loss was in femoral neck and greater trochanter-up to 14% Mir 1 and 6 Month Flights pQCT; noticeable loss of trabecular and cortical bone Collet, et al, 1997 tibia after 6 month NASDA Study of 2 NASA 42 y.o. female and 32 y o. male; short flight negative Miyamoto,et al.,1998 Astronauts calcium balance: 3.0% loss of bmd in L2-4
Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 4 Spaceflight Bone Loss in Humans Flight / Study Fi n ding References Ge mini 4, 5, and 7 4-14 da ys ; Cal c aneus and metacarpal bone density los ses of 2-4% for 5 astronaut s, and 9% for sixth Vos e, 1974 So y u z 9 18 days; 8-10% decrease in cal c aneus density for both cos monauts Birykov and Krasnyk h, 1970 Ap ollo 17 12.6 days; mean Ca lo s s of 0.2% of total body and mean Phosphorus los s of 0.7% of tot al body through increas ed urinary and fecal excretion R a mbaut, et al., 1975 Skylab 2 Missi on No significant bone miner al content c hanges in ar m; cal c aneus los s r eturned to nor m al b y 87th day postfl. Vogel & Whittle, 1976 Long Term Follow-Up of S k ylab Bone D e min. Statistically sig nific a nt lo ss of os calcis min eral in ni ne S k ylab crew member s, 5 year s after flight Tilton, et al., 1980 C o m bin e d U.S. / U.S.S.R. Study of Long Term Flig ht QC T of s pin e; U p t o 8 m o nth s; No los s i n verte bral bodies, but 8% loss in posterior element s (4% los s in volume of attached mus cles); exer cise counter measures onl y partially s u c c e s sful O ganov, et al., 1990 Mir 366- Day Missi on One cos monaut a veraged 10% loss of trabec ular bone from L1, L2, L3; measured by Q CT Grigoriev, et al., 1991 Mir 4.5-6 Month Flights Q D R as ses s ment of B M D; total body mineral los s es averaged 0.4%; most mar k ed local los s was in fe m o ral n e c k a nd gr e ate r trochant er -- up to 1 4% O ganov, et al., 1992 Mir 1 and 6 Month Flights pQ C T; noticeable los s of trabec ular and cortical bone in tibia after 6 months C ollet, et al., 1997 NASDA Stu d y of 2 NASA Astronauts 42 y.o. fe male and 32 y.o. male; short flight; negative cal cium balance; 3.0% loss of B M D in L2-4 Miya m oto, et al., 1 9 98
Prof Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support Spaceflight bone loss in animals Flight /Study Finding References Cosmos 605 Rats; Bone formation reduced in metaphyses of long Yagodovsky, et al.,1976 bones Cosmos 782 Rats; 40% reduction in length of primary spongia As ling 1978 due to reduced formation and increased resorption Cosmos 782? Rats; Osteoblast differentiation in non-weight-bearing Roberts, 1981 site suppressed during weightlessness Cosmos 936 Rats; 30%decrease in femoral breaking strength of Spector, et al., 1983 femora with recovery of normal properties after 25d Cosmos 782&936 Rats; Arrest line separating bone formed during and Turner, et al., 1985 post-spaceflight; defective and hypomineralized bone Rat Tail Suspension, Up to 15 days; Calcium content: tibia =86.2 +1-2.5%, Globus, et al., 1984 1984 vertebra= 75.5 +/-3.5% of control Cosmos 1514 Primates; 5 days: resorption increased during flight Cosmos 1667, 1887, Primates; 13 days; lower mineralization rate and less am t eta,1986 et al. 1990 2044 bone mineralized; longitudinal growth slowed Cosmos 1667 Rats; 7d spaceflight vs 7d tail-sus pension; loss ofVico, et al., 1991 trabecular bone in prox tibial metaph more extensive in flight rats Cosmos 22 Rats; Fracture repair process impaired during flight Kaplansky, 991 osmos Primates; 11.5 days; tendency toward decreased Zerah, et al BMC during fight; only partial recovey 1 month after Rat Tail Suspension, Unloaded bones display reduced osteoblastnumber, Morey-Holton and 1998 growth, and mineralization rate in trabecular bone Globus. 1998
Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 5 Spaceflight Bone Loss in Animals Flight / Study Fi n ding References C osm os 605 Rat s; Bone for mation reduced in m etaphyses of long bones Yagodovs k y, et al., 1976 C osm os 782 Rat s; 40% reduction in length of primar y s pongios a due to reduced for m ation and increa sed resorption Asling, 1978 C osm os 782? Rat s; Os teoblast differ entiation in nonweight-bearin g site s uppres sed during weightles sne ss R oberts, 1981 C osm os 936 Rat s; 30% decrea se in femoral brea king strength of femora with recover y of normal properties after 25d Spe ctor, et al., 1983 C osm os 782 & 936 Rat s; Arre st line s epar ating bone for med during and post-s paceflight; defective and hypomineralized bone Turner, et al., 1985 Rat Tail S uspensi o n, 1984 Up to 15 days; Cal cium cont ent: tibia = 86.2 +/- 2. 5 %, vertebra = 75.5 +/- 3.5% of control Globus, et al., 1984 C osm os 1514 Primates; 5 days; res orption increas ed during flight C ann, et al., 1986 C osm os 1667, 1887, 2044 Primates; 13 days; lower mineralization r ate and less bone mineralized; longitudinal growth slowed C ann, et al., 1990 C osm os 1667 Rat s; 7d spaceflight vs 7d t ail-sus pension; loss of trabecular bone in prox tibial met aph more extensive in flig ht r ats Vico, et al., 1991 C osm os 2044 Rat s; Fracture repair proces s impaired during flight Kaplans k y, et al., 1991 C osm os 2229 Primates; 11.5 days; tendenc y toward decreased B M C during flight; onl y partial rec o vey 1 month after Zerath, et al., 1996 Rat Tail S uspensi o n, 1998 Unloaded bones di spl ay reduced osteoblast nu mber, growth, and mineralization rate in trabecul ar bone M orey-Holton and Globus, 1998
Prof Dava Newman 16.423.J/HST515J Space Biomedical Engineering and Life Support 6 Bedrest/Hypokinesia Studies Models for Weightlessness of spaceflight Study Finding References 5-36 Weeks Bedrest 90 healthy young men; 5% loss of calcaneal minera Schneider and each month mechanical and biochemical McDonald. 1984 countermeasures not success ful 120-day Bedrest Mineralization rate slowed; contradictory results Ⅵco,etal.1987 demonstrate difficulties of bedrest as space analog 17-week bedrest 6 healthy young males: 6 months of reambulation; LeBlanc, et al., 1990 BMD change(p <.05 femoral neck(N)-36 trochanter(1-4.6;%/week(p <.05: FN- 21 +/.05 T-, 27+/- 05; Reambulation %recovery: FN 0.00+/- 06, T0.05 +/-05(prox femur did not recover well 370-day Antiorthostatic Highest losses in foot bones remedial measures Zaichick and Morukov, Hypokinesia Test delay osteoporosis but do not completely exclude it; 1998 results obtained by different methods often conflicting
Prof. Dava Newman 16.423J/HST515J Space Biomedical Engineering and Life Support 6 Bedrest / Hypokinesia Studies Models for Weightlessness of Spaceflight Study Finding Refere n c es 5-36 Weeks Bedrest 90 healt h y young men; 5% los s of c alcaneal minerla each m onth; mechanical and biochemical counterm easures not suc ces sful S chneider and M cDonald, 1984 120- day B e drest Mineralization r ate slowed; c ontradictor y r e s ults demonstrate difficulties of bedres t as space analog Vico, et al., 1987 17- week B e drest 6 healthy young male s; 6 months of reambulation; BMD % c han ge (p < .05): femoral neck (FN) -3.6, tr o c h a nte r (T) -4.6; % / w e e k (p < . 0 5): FN -. 2 1 +/- . 0 5, T -.27 +/- .05; Reamb ulatio n % recovery: FN 0.00 +/- .0 6, T 0.0 5 +/- . 0 5 (p r ox. fe m ur did n ot re c o v e r w ell) Le Blanc, et al., 1990 3 7 0-d a y A nti orth o static Hyp o kin e sia T e st Highest los ses in foot bones; remedial meas ures delay os teoporosis b ut do not c o m plet ely exclu de it; res ult s obtained by different met hods often conflicting Z aichic k and M oru k o v, 1998
Prof Dava Newman 16.423.J/HST515J Space Biomedical Engineering and Life Support Summary of Findings Significant bone loss in weightlessness Calcium excretion increases- negative balance Bone mineral density decreases weight bearing areas: 1-2% per month Osteoblast(builders) proliferation and activity reduced, while osteoclasts(consumers)appear to be unaffected Fracture repair may be impaired Bone strength is reduced
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 increasesœ negative balance ò Bone mineral density decreases œ 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 Research Questions What is the rate of bone loss in critical areas? How does this affect bone strength? What is the risk of fracture? duration of spaceflight activity, gravity level bone habitus: body weight, etc What countermeasures are possible and how effective are they?
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 bone strength? ò What is the risk of fracture? œ duration of spaceflight œ activity, gravity level œ bone habitus: body weight, etc. ò What countermeasures are possible and how effective are they?
Prof dava Newman 16. 423.J/HST515J Space Biomedical Engineering and Life Support Current research Justification Focus on critical weight bearing areas and regions of rapid bone loss(related due to remodeling) lumbar spine proximal femur(hip) 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 9 Current Research Justification ò Focus on critical weight bearing areas and regions of rapid bone loss (related due to remodeling) œ lumbar spine œ 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 Current research 5000 4000 3000 2000 y=4524X+470 1000 r2=71p<.001 04 6 0.8 Neck BMD(gm/cm) Neglects: specific loading condition, body habitus, bone geometry, 3-d density distribution(DXA IS 2-D) Does not exploit engineering theory
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/cm2) ò Neglects: specific loading condition, body habitus, bone geometry, 3-D density distribution (DXA is 2-D) ò Does not exploit engineering theory