Appendix B

Additional, more detailed, information of literature on bone in relation to spaceflight experiments as refered to in Chapter 1.

Table C-a: Overview of studies on bone and spaceflight.

#

Name:

Flight:

Species:

Number of samples:

Groups / Remarks:

Bone Site / Cells:

1

Mack et al.,

1967

Gemini

IV, V, VII

human

Each flight: 2

See Vose 1974.

Os calcis, talus, phalanges (hand), carpals.

2

Vose et al.,

1974

Gemini

IV, V

human

Gemini IV and V: 2

Both commander-pilot and pilot of each flight.

Os calcis.

3

Lutwak et al.,

1969

Gemini-VII

human

Flight: 2

Samples at 10 days pre-flight, in flight and 4 days post-flight.

(Endocrinolic: urine, feces and sweat.)

4

Mack et al.,

1971

BIOSAT.

III

sub-human primate (Macaca Nemestrina).

Flight: 1

Control: 1

Control in identical satellite on Earth.

17 different anatomical sites.

5

Rambaut et al.,

1975

Apollo

17

human

Flight: 3

Flight, preflight and post flight values.

(Endocrinolic; urine and feces.)

6

Whedon et al.,

1975

SkyLab-II

human

Flight: 3

 

(Endocrinolic; urine and feces.)

7

Vogel et al.,

1976

SkyLab-II

SkyLab-III

SkyLab-IV

human

N = 3 for each flight.

 

Os Calcis (left), right radius, right ulna.

8

Tilton et al.,

1980

SkyLab

II, III, IV

human

Flight: 9

1st Control: 5

2nd Control: 3

 

Os Calcis.

9

Yagodovsky et al.,

1976

Cosmos

605

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

22 days

Also a group at R + 27 days.

Right femur, tibia and humerus.

10

Organov et al.,

1991

SALJUT-7

orbital station

human

 

 

human

Flight: total 7

 

 

Hypokinesia: total 9

Flight: 150-237 days.

5 hypokinesia (head down tilt):

a) 120 days no exercise

+ 250 + exercise

b) total 270 days + exercise.

Lumbar vertebral spongy, anterior and posterior side.

11

Morey et al.,

1978

Cosmos

782

Wistar

rat

Flight: 6

Synchronous: 6

Vivarium: 6

Post Flight: 6

Synchronous.: started 5 days after flight.

Also a 26 days post flight group was included.

Tibia.

12

Turner et al.,

1985

Cosmos

782

936

Wistar

rat

Flight: ?

Synchronous: ?

Vivarium: ?

Post-Flight: ?

Half of the flight group killed at R + 25 days.

Tibia.

13

Spengler et al.,

1983

Cosmos

936

Wistar

rat

Basal: 6

Flight: 5

Flight 1xg:5

Synchronous: 5

Vivarium: 10

Synchronous started 4 days later than flight.

Also group at R + 25 days.

Femur, left tibiae.

14

Spector et al.,

1983

Cosmos

782

936

rat

 

See refs for details:

Morey; Science 1978, 1138-41 / Turner; Physiologist 1979, 22, 573-574

Tibia.

15

Wronski et al.,

1983

Cosmos

1129

Wistar

rat

n=11

(some groups

n=5) !?

Synchronous: started 5 days after flight.

Also a flight group with + 29 days post-flight recovery period; post flight all housed in vivarium.

Left tibia, humerus, rib cage (only just after flight).

16

Stupakov et al.,

1989

Cosmos

1129,

bed-rest

Wistar rat,

human (bed rest)

Bed-rest: 9

Rat; Cosmos.

Human; bed-rest study.

Rat: femoral head.

Human: iliac crest biopsy.

17

Simmons et al.,

1983

Cosmos

1129

rat

Flight: 5-7

Synchronous started 5 days after flight.

Alveolar bone, ribs, incisors, dentine.

Post flight: R + 7-11 hrs.

18

Pitts et al.,

1983

Cosmos

1129

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

Flight animals killed 36 hours after reentry.(R+36 hrs.)

Synchronous: R + 4 days

Skinned, eviscerated carcasses (mainly bone + muscle).

19

Cann et al.,

1983

Cosmos

1129

Wistar

rat

Flight: 5

Synchronous: 5

 

Rib cage, feces.

20

Wronski et al.,

1983

Cosmos

782, 936, 1129

rat

 

 

Tibial diaphysis.

21

Eurell et al.,

1983

Cosmos

1129

Wistar

rat

Flight: 5-7

Synchronous: 5-7

Vivarium: 5-7

(the n pertains to the number of vertebral bodies)

1. "direct"

2. R+6 days

3. R+29 days

4th and 5th Lumbar vertebrae (L4 and L5) (cortical + trabecular bone)

22

Jee et al.,

1983

Cosmos

1129

Wistar

rat

Flight: R+0: 7

Synchronous: R+0: 7

Vivarium R+0: 7

All: R+6 days: 6

All: R+29 days: 5

direct

R+6 days

R+29 days

Left tibia, humeri.

23

France et al.,

1982

Cosmos

1129

Wistar

rat

Flight: ?

Flight + 0, 6 and 29 days post flight: ?

Synchronous: ?

direct

R+6 days

R+29 days

Vertebral centrum.

24

Vico et al.,

1987

Cosmos

1514

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

Loaded: tibia-femur.

Unloaded: thoracic + lumbar vertebrae.

During flight the rats are from 13 to 18 days pregnant.

Left femur, left tibia, 3rd thoracic (T3) vertebrae, 3rd lumbar (L3) vertebrae.

25

Pospisilova et al.,

1987

Cosmos

1514

Wistar

rat

Flight: 5

Synchronous: ?

Vivarium: ?

Out of 5 flight rats, 4 gave birth to 12 young rats. Under g during 13th - 18th day pregnancy, rat gave birth at 23rd day.

Samples for neonatal rats at: R+2-3 hrs, and R+15, 30, 100 days old.

Femur and skin from flight offspring rats.

26

Bakulin et al.,

1985

Cosmos

1514

rat

Flight: 5

Synchronous: 5

Vivarium: 5

Flight: 5 pregnant rats (18d pregnant at R, 13 days at launch).

Humerus; proximal and epiphysis.

27

Pospisilova et al.,

1986

Cosmos

1514

Wistar

rat

Flight: 4

Synchronous: 7

Pregnant 13th - 17th day during flight.

Femur.

28

Patterson-Buckendahl et al.

1987

SL-3

rat

Preflight: 6

Flight: 6

Simulation: 6

Preflight: killed at launch.

Flight: R+12.

Flight Controls: 48 hrs. after flight.

3rd Lumbar vertebrae (L3) ® n=6

right humeri ® n=6.

29

 

Wronski et al.,

1987

SL-3

Sprangue Dawley

rat

Flight1: 5

Flight2: 6

Flight Control 1: 5

Flight Control 2: 6

Flight: R+11-17 hrs.

Flight Control: F + 48.

Right tibia shaft, right proximal. humerus and 4th lumbar vertebrae (L4).

30

Simmons et al.,

1986

SL-3

Sprangue-Dawley

rat

Flight: 6

Fl. Control: 6

Flight: R + 12 hrs.

Flight Control: R + 2 days.

Femur and vertebra.

31

Shaw et al.,

1988

SL-3

Sprangue Dawley

rat

PreFlight: 6

Flight: 6

Flight Control: 6

Flight: R+11 hrs.

Flight control: F+48 hrs.

Humerus and tibia.

32

Doty et al.,

1985

SL-3

rat

Flight: ?

Ground: ?

 

Tibiae.

33

Duke et al., 1985

SL-3

rat

Flight: 6

Flight Control: 6

 

Proximal tibia, growth plate.

34

Vico et al.,

1988

Cosmos

1667

Wistar

rat

Flight: 7

Synchronous: 7

Local control: 10

Including 10 French control rats (= local control)

Tibia + femur proximal metaphysis,

8th thoracic vertebrae (T8), 1st lumbar vertebrae (L1).

35

Vico et al.,

1991

Cosmos

1667

Wistar

rat

Flight:7

Synchronous: 7

Suspension: 17

Cosmos and tail Suspension

Right tibia.

36

Pospisilov et al.,

1988

Cosmos

1667

Wistar

rat

Flight: ?

Synchronous: ?

Vivarium: ?

 

Femur, skin.

37

Weingart et al.,

1988

Cosmos

1514

Cosmos

1667

Wistar

rat

Flight: 10

Synchronous: 10

Flight: 10

Synchronous: 10

Cosmos 1514: rat 15 days pregnant at launch

Jaw, molars, incisors, in bone cement, dentine.

38

Morey et al.,

1988

SL-2

human

Flight: 4

Samples: L-24, -18, -3, in-flight, R+0, +30, +10 days.

(Endocrinolic; blood plasma.)

39

Zernicke et al.

1990

Cosmos

1887

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Vivarium (same cages as flight).

6th Lumbar vertebrae (L6).

40

Kaplansky et al., 1990

Cosmos

1887

Wistar

rat

Flight: ?

Synchronous: ?

Vivarium: ?

 

Tibia and 4th-6th lumbar vertebrae (L4-L6).

41

Simmons et al.,

1990

Cosmos

1887

Wistar

rat

Basal: 6

Flight: 6

Synchronous: 6

Vivarium: 6

Basal: L-5 days.

Flight: R+2,4 days.

Synchronous: R+5 days.

Vivarium: R+3-4 days.

Calvaria, mandibles, incisor, dentine and vertebrae.

42

Földers et al.,

1990

Cosmos

1887

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

Immobilization: ?

Also immobilized (8 weeks) rats used.

Post-flight: R+ 4-8 hrs.

Femur-tibia knee joint. (Distal part of femur and proximal part and diaphysis of tibia).

43

Doty et al.,

1990

Cosmos

1887

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Flight: R+2 days .

Tibia (proximal + some diaphysis and shaft). Tibio-fibrular junction (TFJ).

44

Duke et al.,

1990

Cosmos

1887

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Post-flight: R+53.5 hrs.

Right tibia heads and growth plates.

45

Garetto et al.,

1990

Cosmos

1887

Wistar

rat

Basal: 4

Flight: 4

Synchronous: 4

Vivarium: 4

Post-flight: R+55 hrs.

Fibroblast like osteoblast precursors in PDL of maxilla first molar.

46

Mechanic et al.,

1990

Cosmos

1887

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Post-flight: R+2 days.

Right femur.

47

Zerath et al.,

1990

Cosmos

1887

rat

monkey

Flight: n=5

Flight:n=2

Synchronous controls for the monkeys were the same individuals, and was performed only 43 days after the actual flight.

Iliac crest biopsies (monkey).

Left humerus (rat).

9th Thoracic vertebrae (T9).

48

Doty et al.

1992

Cosmos

2044

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

 

Tibia (tendon of mid-metatarsal area).

49

Zerath et al.

1991

Cosmos

2044

 

Cosmos

2044

rhesus

monkey

 

Wistar

rat

Flight: ?

Synchronous: ?

Vivarium: ?

Flight: 5

Synchronous: 5

vivarium: 5

Rat samples: R+11days R+34 days

 

 

R + 6-10 hrs.

Iliac crest (monkey).

 

 

Left humeri

9th Thoracic vertebrae (T9).

50

Garetto et al.,

1992

Cosmos

2044

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 4

Post-flight: R+8.5-11 hrs.

Fibroblast like osteoblast precursors in PDL of maxilla first molar.

51

Kaplanski et al.,

1991

Cosmos

2044

Wistar

rat

Flight: 5

Synchronous: 5

Vivarium: 5

Suspension: 5

Also tail suspended rats.

Post-flight: R+4-7 hrs.

Fractured fibula and intact tibia.

52

Pedrinimille et al.,

1992

Cosmos

2044

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Suspension: 5

 

Invertebrial disks, L3-4 to L6-S1.

53

Vailas et al.,

1992

Cosmos

2044

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Post-flight: R+3 - 11 hrs.

Humerus, femur

(cortical bone).

54

Vico et al.,

1993

Cosmos

2044

Wistar

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5

Total number of rats per group 10:

5 used in this study, 5 used for bone repair studies by Kaplansky (Kaplansky et al., 1991).

Post flight: R+6-10 hrs.

Left proximal tibia + femur, 5th dorsal vertebral body (D5), 2nd lumbar vertebral (L2) body and the femoral fossa trochanteri.

55

Arnaud et al., 1992

Cosmos 2044

rat

Basal: 5

Flight: 5

Synchronous: 5

Vivarium: 5 Suspension: 5

 

(Blood plasma.)

56

Schneider et al.,

1992

Mir

human

 

Only flight subjects. In space during 131-312 days.

Pelvis, femoral neck, trochanter.

57

Backup et al.,

1994

STS-41

STS-52

Sprangue-Dawley

rat

4 day mission:

Flight: 8

Ground: 12

10 day mission:

Flight: 6

Ground: 6

Post flight: R+4-6 hrs.

SPE-1: STS-41.

SPE-2: STS-52.

Calvaria, left femur, humeri, radii and ulnae periostea.

 

Table C-b: Overview of studies on bone and spaceflight.

#

Name:

Flight:

Technique:

Results / Discussion:

1

Mack et al.,

1967

Gemini

IV, V, VII

Gemini 4: photos at: L-9 en L-3 days en L-0; R+0; R+16 and R+50 days

Gemini 5: L-10, -4, -2 and - 0 days; R+ 0, 1, 10, 58 days. Gemini 7: L-10, -3, -0 days; R+0, 1, 11, 57 days. 125I source, monoenergetic photons.

In this very extensive study all bone sites lost bone, especially in the appendicular skeleton.

Some calibration mistakes were made see: "Vose, 1974"

2

Vose et al.,

1974

Gemini

IV, V

Automatic scanning of röngenograms.

Correction on Macks paper on bone density (Mack, 1967).

Gemini 4: 2,9 and 3,8% loss } experiment errors is

Gemini 5: 9,2 and 2,5% loss } 2.5%.

3

Lutwak et al.,

1969

Gemini-VII

Ca2+, PO43-.

Great interindividual variability. Calcium balance less positive in both astronauts. In one subject significant increase in urinary Ca excretion. Both subjects show increased dermal Ca2+ and PO42- loss. Also changes in other ions (S2-, Na+, K+, Mg2+and Cl-).

4

Mack et al.,

1971

BIOSAT.

III

X-ray, bone density by radiography.

Average loss in flight animals of 4,5%. Major losses in patella, distal end of the ulna, the wrist (= capitate) and the hand phalange 4/2. Also losses in control animal probably due to immobilization.

5

Rambaut et al.,

1975

Apollo

17

Atomic absorption spectrometry for calcium. Auto analyzer techniques for phosphorus.

Increase in urinary and fecal P excretion during flight. Increase in fecal calcium excretion during flight.

0.2% total body calcium loss, 0.7% total body phosphorus loss. Reported changes could also, besides hypogravity unloading, be the result of disturbances due to gastrointestinal absorption.

6

Whedon et al.,

1975

SkyLab-II

Food intake registration, urinary and fecal calcium and phosphorus excretion. Ca, P, N, K, Na, and Mg balance studies.

Urinary Ca increased gradually during flight. Fecal Ca excretion did not change. Calcium balance became negative or less positive compared to preflight values. Increased excretion and negative balance of P and N.

Significant loss of K, Na and Mg in flight.

7

Vogel et al.,

1976

SkyLab-II

SkyLab-III

SkyLab-IV

Photon absorptiometry: 125I source, monoenergetic photons. Samples at: L-30, -15, -5 days; R+0, 1 en 7 days and thereafter.

Data is quite variable. Some measurements also displays an increase in BMD.

Lowest decrease was 7.9%, greatest increase 3.1%. Overall there was a negative trend, especially in the os calcis and right radius, there was however, a slight increase in BMD in the ulna.

8

Tilton et al.,

1980

SkyLab

II, III, IV

Photon absorptiometry.

Flight crew significant of average bone loss compared to same control group as original, but after 5 years exercise and diet both directly effecting bone varied ad lib over these 5 years.

9

Yagodovsky et al.,

1976

Cosmos

605

Histology, LM, EM, morphometry.

Half of the flight samples showed osteoporosis of the metaphysis, usually combined with a decrease of the mass of the primary spongiosa near the epiphyseal cartilaginous plate. It suggests that growth could have been inhibited during flight.

LM and EM of flight bones showed the presence of wide osteocyte lacunae with could have been produced by perilacunar osteolysis. Some of the phenomena were also seen in synchronous samples but not as pronounced as in flight.

A 27 day post flight period at 1xg was not enough to return to control values.

10

Organov et al.,

1991

SALJUT-7

orbital station

Quantitative computer tomography, mineral density and DPA (dual photon absoptiometry).

Hypokinesia: 50 head down tilt.

Changes in mineral density of lumbar vertebrae in cosmonauts are multidirectional, their magnitudes do not show any correlation with flight duration. Similar changes are seen in hypokinesia study (370 days) and are not related to bed-rest time either. Hypermineralization of specific vertebral segment is more often related to inadequate or lacking countermeasures. There is a decrease in mineral density in the proximal femur epiphysis. This is more constant in direction (decrease) and regular. The authors state that the results of bone mineral density measurements with non-invasive methods (CT, DPA) are not directly related to the mechanical bone strength: other methods should be used in parallel.

11

Morey et al.,

1978

Cosmos

782

Tetracycline injection at L-3 (flight), L-8 (synchronous), R+3 and R+26. Morphometry. Arrest lines.

Periosteal bone formation rat decreased significant by 47%. Arrest lines: suggest a complete cessation of bone growth during flight. Defects were corrected in a 26 day post-flight period. No change in bone resorption.

12

Turner et al.,

1985

Cosmos

782

936

Micrographs, UV-LM, SEM, TEM.

All rats (both flights) labeled with tetracycline at L-1 and at R+3 days (Cosmos782) and R+4 days (Cosmos 963).

Defect at periosteal surface of tibia; an arrest line. In arrest line: abnormal collagen orientation; hypomineralization.

"Arrest lines are located at interface of bone formed in space and that from post-flight".

13

Spengler et al.,

1983

Cosmos

936

Femur: mechanical test and geometry.

Tibia: morphology on thin sections.

In the femur significant torque, stiffness, energy in g group compared to in-flight 1xg.

In femur as well as tibia no significant difference in geometry between g, 1xg flight and synchronous.

In flight 1xg substantially enhanced bone strength, possibly by promoting more normal tissue maturation.

14

Spector et al.,

1983

10

Cosmos

782

936

Tetracycline, arrest-lines, SEM, TEM.

Cessation of periosteal bone formation does not occur on places where intrinsic muscle forces continue to act on the tibia.

Percentage change in bone formation rate on various sides ranging from -16 to -49% for flight compared to controls.

Arrest lines mineralization defect, related to abnormal organic matrix.

15

Wronski et al.

1983

Cosmos

1129

Tetracycline labeling at launch -3d en recovery +5D. UV histology, MERZ grid analysis, Arrest lines.

Significant less periosteal bone formation in the humeral and tibial diaphysis (44%). No change in periosteal bone formation in the rib. In periosteal bone formation in tibia during post flight period: significant. No change in periosteal bone formation in humerus during post flight period. No differences in medullary area in all groups ® no gross change in endosteal resorption activity. Relation in weight bearing on bone site: tibia > humerus > rib (also lower formation rate plays a part).

16

Stupakov et al.,

1989

Cosmos

1129,

bed-rest

Biomechanical analysis, acoustic emission.

Significant decrease in stress absorbance capacity of flight samples at 6 and 29 days post flight, no difference directly after flight. Also decrease in bone mechanical parameters of bed-rest study (370d en 120d). Training partially counter-acted the decrease.

17

Simmons et al.,

1983

Cosmos

1129

At L-3d tetracycline injection: again after 5 or 27d.

Post-flight; density gradient fractionation; Ca, P, Hy-Pro; sulfur, Histomorphometry.

Differences in response of jaws and ribs probably related to size of their respective osteoprogenitor pool. There was an overall decrease in turnover rates without creating a negative balance:. Microgravity did not disrupt the normal coupling of bone formation and bone resorption. g did not alter periosteal bone formation rate in ribs and regions of mandibles. In g ,bone formation-calcification rates were impaired at sites in jaw of non-continuous muscle. Under g indications of a delay of maturation of bone mineral and matrix. At 29 days post-flight: all values had returned to normal. It is concluded that also most of non-weight bones are at risk to g.

18

Pitts et al.,

1983

Cosmos

1129

Whole body composition of all kinds of parameters (fat, water, etc.). Mainly bone + muscle = musculoskeletal system (+ other parts).

Reduced fraction of total body water, shift from skin to viscera. Marked (significant) reduction in the fraction of bone minerals. A relative net increase in total muscle mass. Many of the differences could also be due to age difference between the groups.

19

Cann et al.,

1983

Cosmos

1129

Calcium isotope tracer techniques. Ca, Mg, K, Zn, Na content. Ash weight.

No differences in fecal excretion mass. No significant changes in bone resorption or bone formation.

A significant increase in Na, K and Zn excretion.

20

Wronski et al.,

1983

Cosmos

782,936, 1129

Tetracycline, histomorphometry.

Decreased periosteal bone formation in all flight tibiae: 44-37% decrease.

21

Eurell et al.,

1983

Cosmos

1129

Ca, collagen, keratosulphate, chondroitin sulfate, (histochemistry).

Decreased Ca content in flight (significant), only at R+6 days returned to normal at R+29d. (no change at day R+0).

Significant higher keratosulphate in flight+0 and flight+6 days compared to all other groups. No significant changes in chondroitin sulfate and collagen content. It is argued that all these changes are indicative for an increased aging process.

22

Jee et al.,

1983

Cosmos

1129

Histomorphometry, declomicine (= tetracycline).

Twenty nine days post-flight: in tibia flight significant in trabecular bone volume compared to synchronous. 0 days post-flight: flight sign in trabecular bone volume compared to synchronous in humerus. Significant more fat (in marrow) in flight compared to synchronous just after recovery: returned to normal at 29 days post flight. Reduced number of osteoblasts at 0,3 mm from the cartilage metaphyseal junction (significant). No changes in osteoclast numbers. Hypothesized that the effects of spaceflight are not due to osteoblasts or osteoclasts but are due to incomplete/retarded growth of the calcified cartilage of the growth plate => less mineralized trabeculae ® less bone. This would also reflects the retarded growth in length.

23

France et al.,

1982

Cosmos

1129

Atomic absorption spectrophotometry, specific ion electrodes, Vit-C, colorimetric analysis. Na+, K+, Ba2+, Ca2+, Mg2+, Sr2+, Y2+, Pl2+, Mn2+, F-, Cl-, PO43- content.

Only significant change in calcium content: lower in flight compared to synchronous. Due to unchanged PO43- and a decrease in Ca content => indication for incomplete osteoid mineralization.

24

Vico et al.,

1987

Cosmos

1514

Bone histomorphometry, TRAcP.

The only flight data with pregnant rats and bone. Bone mass was not changed. Mean thickness of osteoid seams and endosteal resorption thickness in long bones was unaffected. Osteoclast number: in thoracic (sign), and in lumbar (NS). This could also be due to hormonal changes due to a combined pregnancy and g effect. No changes in osteoblast parameters in all bone sites.

25

Pospisilova et al.,

1987

Cosmos

1514

Pepsin digestion; collagen Type I, II, III, effects both in bone and skin (hormonal influence ?).

More neonatals of g group died (19%) compared to synchronous (2.5%), vivarium (0%).

In the bones of the flight rats offspring there was an increased collagen solubility, a fall in the ratio Hy-Pro -glycoproteins, a slowly increase in Type I collagen and persistent higher values of Type II and III collagens. As is seen by relatively more Type III collagen => matrix is less mature. Concluded a retarded maturation of protein components, this is persisting until maturity.

26

Bakulin et al.,

1985

Cosmos

1514

Volume-weight, ash weight, Mg, Ca, Zn, P, K, Na, silicon content, mechanical strength (stress-strain, Youngs modulus).

A significant in organic + mineral (Ca) content } decreased Ca/P ratio, mainly due to

A significant in P content } P content

A significant in mechanical properties; ultimate strength and relative strain.

27

Pospisilova et al.,

1986

Cosmos

1514

Collagens Type I, II, III.

Significant reduction in collagen Type I in flight, and significant higher overall amount of peptides in flight samples.

28

Patterson -

Buckendahl et al.

1987

SL-3

Three point bending: Ca, Pi, Osteocalcin, Mg, collagen, Hy-Pro.

In vertebrae: Total bone mass, Ca, Pi, Mg, osteocalcin: all significant in flight compared to flight simulation. Hy-Pro slightly increased in flight. Increased could be due to a: a stimulation of synthesis or b: a reduced degradation. In humeri: mass, mineral, osteocalcin; significant in flight, total Hy-Pro unchanged. All results in a mineralization deficit. Bone strength data suggest a change in bone quality related to the mineralization of bone matrix.

29

Wronski et al.,

1987

SL-3

Calceine label: large rats at L-9 and L-2 days.

Histomorphometry: using labels for large rats and non-labeled for small rats.

Large flight rats: - tibial diaphysis: significant in periosteal bone formation rate compared to controls, proximal humerus and lumbar vertebrae: Long bone growth: (NS), no change in trabecular bone volume, proximal humeral metaphysis: osteoclast surface and number: (NS), lumbar vertebrae: unchanged osteoclast surface en number.

Small flight rats: vertebrae: trabecular. bone vol. 25% : (NS), primary spongiosa of proximal tibial metaphysis: osteoblast parameter: (NS). In general only trends are found. The number of samples was to small to detect significant differences.

30

Simmons et al.,

1986

SL-3

Gradient density fractionation, X-ray diffraction. Ca, Hy-Pro and P, Mg content. Ca/P ratio and ash weight.

Flight femoral diaphysis contained more Pi then the flight control. In the thoracic vertebrae the flight samples have a lower ash weight. In general there was a shift of matrix profiles and mineral moieties towards both higher (femurs, vertebrae) and lower (vertebrae) portions. All indicates a decrease in bone growth/ turnover in flight samples and a relative increase in skeletal maturation. X-ray diffraction of the vertebrae indicate that spaceflight is associated with a decrease in apatite crystal size / perfection. This in turn could be causing reduced mechanical strength.

31

Shaw et al.,

1988

SL-3

Mechanical testing (3-point bending tests), bone morphometry (gross), bone density.

Total length of tibia and humerus of g significant compared to flight control: with age correction only humeri remained significant. No significant change in diaphyseal cross-sectional morphologies of tibia nor humeri. Tibia diaphyseal cross-sectional densities (sign) in flight: NS in humeri. g impeded the mechanical maturation (strength, stiffness) of bone: more pronounced in tibia than in humerus.

32

Doty et al.,

1985

SL-3

AlP, AcP, dipeptidyl peptidase-II, LM, EM and histomorphometry.

No changes in AlP, AcP, Dipeptidyl peptidase-II. Tendency to reduced cytoplasmic area => less osteoblastic activity ® less matrix synthesis.

33

Duke et al.,

1985

SL-3

LM, zone heights morphometry. Freeze substitution for microanalysis.

Although there were some technical problems, flight animals revealed a low Ca, P, K and Na content, while Mg was not affected. The S levels were much less in flight compared to ground. All the zones within these long bones, resting -, proliferating -, and hypertrophic/calcification zone were reduced in length. It was concluded that even short spaceflight can alter bone mineralization.

34

Vico et al.,

1988

Cosmos

1667

Local control rats: injected with tetracycline. Bone histomorphometry, TRAP.

Tibia: trabecular bone volume , trabeculae were decreased in number and thickness. Formation activity at trabecular and endosteal levels . Resorption activity unchanged. Femur: trabecular bone volume: (NS). Osteoclastic and osteoid parameters unchanged. No changes in bone mass and bone resorption in thoracic and lumbar vertebrae.

35

Vico et al.,

1991

Cosmos

1667

Bone histomorphometry, TRAP, tetracycline (only suspended rats).

In both unloading experiments (space flight as well as tail suspension) a clear and significant decrease in bone formation parameters. Difference in osteoclastic activity: no change under g while a significant increase osteoclastic parameters with tail suspension. Under microgravity a sign . in tibial metaphysis trabecular and endosteal bone formation.

36

Pospisilov et al.,

1988

Cosmos

1667

Collagen Type I and III: pepsin digestion (soluble/insoluble), chromatography.

Total amount of collagen (Type I+III) (sign) by 35% in g (in femurs). No change in total collagen in skin. Pepsin-soluble collagen (Type I+III) (sign) in g in femurs; in skin (sign). Type III pepsin soluble insoluble (sign) in g femurs: in skin. => all indicates: high turn-over; active remodeling, bone and skin: => systemic factors.

37

Weingart et al.,

1988

Cosmos

1514, 1667

Carbonatapatite concentration by infra-red spectroscopy.

Significant in carbonatapatite only in male rats dentine, cement and bone, no changes in female rats. This could be a result of a combination of a short flight and different hormone levels compared to males rats.

38

Morey et al.,

1988

SL-2

Bone related hormones (1,25)-, (25)-, (24-25)- Vit D, PTH and total Ca, P and albumin.

Significant of early in-flight 1,25vitD levels ® returned to normal later in flight: could be due to reduced food intake and could transiently have activated bone remodeling. No changes in PTH levels. Calcium, P, albumin, 24(OH)D and 24, 25(OH)2D levels , all normal.

39

Zernicke et al.

1990

Cosmos

1887

Mechanical testing: compression Hy-Pro, Ca, P, hydroxypyridinoline, collagen cross-links.

Re-entry forces and transport not mimicked for synchronous rats. Flight: body weight sign compared to synchronous and vivarium. Weight L6: NS in flight compared to synchronous, vivarium en basal. A 47% decrease in compression stiffness in flight: (NS) compared to synchronous and vivarium. Initial maximal load in flight samples was -18% compared to synchronous (NS). Average linear load in flight: (NS) synchronous and vivarium. No change in Ca, P en Hy-Pro concentrations among all groups. Cross-links: Flight sign compared to vivarium: NS compared to synchronous and basal. "Combined biomechanical and matrix biochemistry results suggest that the effects found were material as well as structural in nature". Slowed maturation of trabecular bone in vertebral bodies of rapidly growing rats.

40

Kaplansky et al.,

1990

Cosmos

1887

Bone histomorphometry, TRAcP.

Reduction of bone in primary and secondary spongiosa shown as a decreased number and thickness of trabeculae in the flight tibia. Thickness and length of the epiphyseal growth plate was diminished in flight samples. Decrease in number and activity of osteoblasts in tibial metaphysis, while number of osteoclasts increased in primary spongiosa of flight bones. Nearly identical patterns were seen in the vertebrae. No significant changes on compact bone.

41

Simmons et al.,

1990

Cosmos

1887

Bone density fractionation, X-ray diffraction, Ca, P and Mg content. Ash weight.

In calvaria: mineralization profiles to lower weights => indicates impaired mineralization. Space flight did not much alter the composition of dentine. In g calvaria: overall mineral composition not changed. In g L5 vertebra: overall mineral composition not changed. In g mandible: overall mineral composition not changed. In g: hydroxyapatite crystals in mandibles significant smaller, in calvarae lower Ca/P and Ca/Mg ratios tendencies => indicative for immature bone. "g not adversely effects the maturation of newly formed bone only in weight bearing bones, such effects occur throughout the skeleton".

42

Földes et al.,

1990

Cosmos

1887

Histology, histomorphology.

Density and volume of spongious trabecular of metaphysis (sign). Density in diaphysis and the density of trabeculae (sign). Reduction of bone formation parameters. Increase in osteoclastic index, osteoclast activity, Howships lacunae osteolysis. No significant changes of flight and immobilization, except for osteoid volume: in immobilization.

Some synchronous parameters more closely related to flight in stead of vivarium => indication for stress/ immobilization.

43

Doty et al., 1990

Cosmos

1887

EM, AlP, NADPase lipid staining, LM and hisomorphometry. (NADPase is involved in collagen synthesis and secretion, localized in Golgi.)

AlP in endothelial and perivascular cells at the LM level was decreased in flight samples of diaphyseal bone compared to control. Significant more blood vessel profiles in flight bones compared to synchronous controls (could also be due to re-entry hypergravity and impact). No differences in bone, bone marrow area or periosteal perimeter.

44

Duke et al.,

1990

Cosmos

1887

EM, LM, histomorphometry, HE, Tol. Blue, collagen orientation, collagen fibrils.

Significant lager proliferation zone in flight. Reduced reserve and hypertrophic/calcification zone in flight. Significant more cells in flight proliferation zone per column. Total number of cells significant in flight samples. Collagen fibrils were wider in flight compared to synchronous. All results possible partly an effect of g and recovery at 1xg. In general, decreased length of the tibia and an impaired mineralization.

45

Garetto et al.,

1990

Cosmos

1887

Nuclear morphometry / volume analysis.

Flight: significant shift of A-A (osteoblast progenitors), cells, -40%, towards C-D (pre-osteoblasts) cells, +42%. There was also in increase in fibroblast like cells near the bone surface. This is probably due to 55 hours recovery time. This would mean a strong recovery of osteoblast precursors cells. Very significant increase in adrenal weight of flight animals. This could be a systematic response due to fluid shift or hormonal environment. Also note age difference of rats.

46

Mechanic et al.,

1990

Cosmos

1887

SEM image analysis, element analysis, biochemistry (powdered bones (SPEX)), collagen content, cross-linkage, osteocalcin (OC), Ca, P content.

Significant of mineral and osteocalcin in distal half of femur diaphysis. Reduced collagen content and evidence of increased synthesis in proximal half of femur diaphysis. Longitudinal gradient of decreasing mineralization towards distal diaphysis (with X-ray microtomography).

47

Zerath et al.,

1990

Cosmos

1887

Calcium label, histomorphometry, osteoblast apposition rate, osteoclasts, calcification rate, trabecular bone volume.

Monkey: significant in calcification rate in flight compared to synchronous. Rat: bone mass in humeral metaphysis and vertebral area. No changes in other parameters investigated.

48

Doty et al.

1992

Cosmos

2044

LM/EM, AcP, AlP, TEM, silver stain for collagen.

Non significant reduction of osteoblast activity/differentiation in flight compared to synchronous. No confirmation of results of Cosmos 1887 in the vascular system ® recovery period ? Randomly organized collagen fibrils in flight tendons compared to synchronous. Collagen fibrils: no change in periodicity in flight compared to synchronous samples.


49

Zerath et al.

1991

Cosmos

2044

 

 

Cosmos

2044

Calceine label injected (a) 1d before launch, (b) at re-entry, (c) before ground sim, (d) at the end of the simulation (day 34), trichrome staining: histomorphometry.

See the above + osteoclast indexes.

(Humerus is weight bearing in the rat while thoracic vertebra is not.)

All results from cancellous bone tissue! Flight: sign mineral apposition rate. Flight: sign mineralizing surface.

Diminished iliac crest bone mineralization activity.

 

 

Proximal humeral metaphysis + 9th vertebral body:

humerus : bone volume, osteoblast surface (all sign) , eroded surface (sign)

vertebrae: bone volume (NS), osteoblast surface (NS), eroded surface (NS)

general : mineralization activity, bone mass: a bone cell activity dissociation.

50

Garetto et al.,

1992

Cosmos

2044

Nuclear volume analysis and widths of PDL.

No changes in osteoblast histogenesis data. Suggest that recovery time is important factor in these responses.

51

Kaplanski et al.,

1991

Cosmos

2044

Bilateral fracture of fibula in diaphyseal central portion combined with histomorphometry.

Size of fibula calluses and strength of consolidated bone fragments were lower in flight compared to synchronous; callus in flight was smaller than in synchronous. In flight callus more fibrous compared to synchronous. ® significant more cartilaginous. Number of osteoclasts in flight per surface unit of spongy bone of the callus significant compared to synchronous. In tibia: osteoporosis in trabecular bone of proximal metaphysis; reduction of bone in primary and secondary spongiosa. Decrease of epiphyseal cartilage growth plate and primary spongiosa zone in flight compared to synchronous: also number of osteoclast in flight compared to synchronous. In general there was an inhibition of fracture healing in flight. Inhibition in flight of growth. Disorder in mineralization (= osteoid, + number of osteoblasts). in flight of osteoclasts. Osteoporosis in flight. Suspension model => good model for g => same effects as seen in flight.

52

Pedrinimille et al.,

1992

Cosmos

2044

LM, EM, biochemistry, proteoglycans (PGs), collagen, cross-linking.

No significant difference in body weight between flight, synchronous and tail suspension of the rats. No significant changes between flight and synchronous in collagen content, PG content, LM, EM, hexuronate content, or release, cross-linking of collagen. Significant difference only in annuli weight: flight < synchronous, and significant larger collagen to PG ratio in flight compared to synchronous. (For statistical evaluations, most data compares flight with all three other control groups combined .)

53

Vailas et al.,

1992

Cosmos

2044

Length, thickness, density, 3-point bending, morphometry, ultrasonic testing, collagen cross-links, Ca, Hydroxyproline content.

No sign differences between flight and synchronous in any parameter. It is argues that this was due to the relatively old age of the rats resulting in a more "quiescent" cortical bone.

54

Vico et al.,

1993

Cosmos

2044

Bone histomorphometry, enzyme histochemistry (TRAcP).

Various differences between flight+synchronous versus vivarium, probably due to physiological stress. In the flight samples there was a significant decrease in width of primary sprongiosa of proximal tibia versus synchronous. Significant increase in number of osteoclasts per mm and percentile active resorption surface in femoral fossa trochantiri (flight versus synchronous). Significant increase in trabecular separation in lumbar vertebral body in flight compared to synchronous.

55

Arnaud et al., 1992

Cosmos 2044

Plasma parathyroid hormone (PTH), calcitonin, Ca, Mg, PO4 ,total protein, creatinine.

There were increased levels of phosphate, creatinine and total protein in flight animals (significant). PTH levels were slightly elevated in flight animals (significant). Flight animals also the lowest calcitonin levels, but these were only statistically different from the vivarium group.

56

Schneider et al.,

1992

Mir

Whole body BMD, DEXA + exercise of cosmonauts.

After flight: increase of BMD in head (significant) 4,21.2%, loss in pelvis 7.42.1% (significant) ® 5,02,2% femoral neck, 9,12,8% trochanter. Also in flight lean body mass => fat muscle mass (significant). Concluded that exercise of cosmonauts minimized muscle atrophy without inhibiting the loss of bone.

57

Backup et al.,

1994

STS-41

STS-52

Tetracycline and calceine labeling. Bone histomorphometry, total cellular RNA, Northern blot analysis of osteocalcin and collagen Type I.

Radial bone growth was unchanged in humeri during the 4 day flight, but significant decreased during the 10 day flight group. Osteocalcin (4 and 10 day flight) and precollagen Type-I (10 day flight) mRNA levels were significant decreased in long bones and calvariae periosteal cells after spaceflight.


With minor changes published in: Jack J.W.A. van Loon, J. Paul Veldhuijzen, Elizabeth H. Burger. Bone and space flight: an overview. in Biological and Medical Research in Space, Edt. D. Moore, P. Bie and H. Oser. Springer-Verlag Berlin Heidelberg, Chapter 5, 259-299, 1996.

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