Comprehensive Physiology Wiley Online Library

The Skeleton and its Adaptation to Gravity

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Evolution and Bone
2 Skeletal Physiology
2.1 Bone Cells
2.2 Skeletal Tissue
3 Musculoskeletal Mechanics
3.1 Gravity and Static Equilibrium
3.2 Activity and Dynamic Equilibrium
3.3 External Loading History
3.4 Muscle and Bone Forces
3.5 Bone Mechanical Properties
3.6 Biological Scaling
3.7 Mathematical Models of Adaptation
3.8 Functional Adaptation to Altered Loading
4 Calcium Metabolism
4.1 Total Body Calcium
4.2 Calcium Kinetics
4.3 Calcium Balance
4.4 Distribution of Mineral in the Skeleton
4.5 Calcium Homeostasis and the Calcium Endocrine System
5 Bone Cellular and Tissue Adaptation
5.1 In Vivo Bone Tissue
5.2 Organ Culture
5.3 Bone Cell Cultures
6 Biomineralization
7 Summary
Figure 1. Figure 1.

Artist's concept of a typical long bone. The sagittal or longitudinal section through the entire bone is depicted in the figure at the left. The three major parts of the bone, the epiphysis, metaphysis, and diaphysis, are bracketed to show the extent of each region. The periosteum is the outer surface of the bone while the endosteum is the inner surface of the bone. Bone marrow is found in the marrow cavity or medullary canal. The enlargement in the upper right is a longitudinal section of cancellous bone from the epiphyseal–metaphyseal region containing three trabeculae. Cancellous bone is composed of multiple trabeculae. During growth, calcified cartilage is usually converted to bone as the trabeculae elongate; bone is layed down on the surface of cartilage in the primary spongiosa while almost complete replacement of cartilage occurs in the secondary spongiosa. The enlargement in the middle of the figure is a cross section of cortical bone with Haversian systems where internal remodeling occurs. The enlargement at the lower right shows the different bone cells beginning with inactive lining cells, active osteoblasts (bone‐forming cells), osteocytes (osteoblasts trapped in mineralized matrix) that form an extensive canalicular system throughout the bone, and an active osteoclast (bone‐resorbing cell) forming a Howship's lacuna on the bone surface.

Figure 2. Figure 2.

Digitized fluorescent image of a cross section of bone from the tibia just proximal to the tibiofibular junction. The bone was labeled by injecting fluorescent bone markers at the same concentration (15 mg/kg) at different times during the experiment. The distance between the labeled rings shows the amount of bone growth between injections. The bone section is from a ground control rat for the 9 day Spacelab Life Sciences 1 experiment. Label 1 is a calcein dye injected 12 days before launch, which was about 1 mo before the animal was euthanized. Label 2 is a tetracycline derivative (demeclocycline) given 7 days after the first label to bracket preflight bone formation. Label 3 was injected 4 days after the second label (1.5 days before launch) due to a launch delay. Label 4 (calcein) was given shortly after the shuttle returned from its 9 day mission. The distance from label 4 to the bone surface represents the 9 day period of postrecovery growth. The most rapid growth occurs on the outer surface where muscle is attached.

Figure 3. Figure 3.

The influence of gravity and activity “intensity” on the external forces imposed on the body. On Earth and Mars during quiet standing the gravitational force is supported by body weight, but body weight on Mars is only about 40% of Earth body weight. Inertial forces during running on either Earth or Mars increase peak support force levels to 2–3 times body weight 94. Even so, external and internal musculoskeletal forces generated during running on Mars are only on the same order of magnitude as walking on Earth. Floating in space exerts no external forces on the body.

Figure 4. Figure 4.

The percent change in body constitutents of young rats from 1G values to 0G (Cosmos 1129) or 2G (centrifuge). Data for 0G are from Pitts et al. 196.

Redrawn from Pace et al. 186
Figure 5. Figure 5.

A diagrammatic illustration of the way in which the intestine, kidney, and bone adjust the distribution of calcium to meet the functional demands of reduced, normal, and increased gravitational loads on the skeleton. Reading from the top down and assuming a fixed amount of dietary calcium for all three situations, intestinal absorption is reduced, normal, and enhanced. The increased fecal excretion during immobilization, a model for reduced gravity, is due not only to a decrease in intestinal calcium absorption but also to increased endogenous fecal calcium, the term used for calcium secreted into the lumen of the intestine then lost in epithelial cells and in bile 96. Normal extracellular fluid (ECF) is considered to be quite stable, averaging 2 mg/kg. We are unaware of any data on ECF during exposure to high gravitational loads or exercise. In acute disuse osteoporosis, renal calcium excretion is augmented, a phenomenon referred to as resorptive hypercalciuria, to indicate its association with increased bone resorption and suppression of the parathyroid/1,25‐dihydroxyvitamin D‐axis 233. During exposure to high gravitational loads, renal conservation of calcium through reduced urinary excretion, compared to normal, is not observed. At the whole body level, bone turnover increases with mobilization of mineral from resorption exceeding formation which tends to be depressed only in the unloaded bones. Bone formation is increased in the weight‐bearing regions of the skeleton. The low, normal and increased shading represents the amounts of whole body bone mineral that are the result of these adaptive changes. The sources for the quantitative aspects of adaptation are from the observations in human adults by Heaney 95, Neer et al. 176, LeBlanc and Schneider 134, LeBlanc et al. 135, Silverberg 223, Ragan and Briscoe 201, and in rats by Yeh and Aloia 282,284.

Figure 6. Figure 6.

Sequence of events in the calcium endocrine system that reduces or provides available mineral from intestinal absorption following exposure to low or high gravitational loads on the skeleton. Bone tissue responds to a decrease in gravitational load by the release of calcium ions into the circulation. The increase in serum calcium depresses circulating concentrations of parathyroid hormone which in turn reduces the formation of 1,25‐dihydroxyvitamin D and the intestinal absorption of calcium. Negative calcium balance is augmented by increases in urinary calcium, and in some situations, increases in endogenous fecal calcium (not shown). The response to an increased gravitational load is deposition of calcium in bone that is followed by a change in serum calcium that depends on adequacy of hydration, change in blood pH, and/or level of dietary calcium. Parathyroid hormone and 1,25‐dihydroxyvitamin D may or may not increase, depending on the adequacy of dietary mineral. Intestinal calcium absorption is increased and calcium balances become more positive.

Figure 7. Figure 7.

Hypothetical scheme that shows parallel responses of the calcium endocrine system and the skeleton to spaceflight. Cellular sites of interaction are not detailed. See SUMMARY for further discussion.



Figure 1.

Artist's concept of a typical long bone. The sagittal or longitudinal section through the entire bone is depicted in the figure at the left. The three major parts of the bone, the epiphysis, metaphysis, and diaphysis, are bracketed to show the extent of each region. The periosteum is the outer surface of the bone while the endosteum is the inner surface of the bone. Bone marrow is found in the marrow cavity or medullary canal. The enlargement in the upper right is a longitudinal section of cancellous bone from the epiphyseal–metaphyseal region containing three trabeculae. Cancellous bone is composed of multiple trabeculae. During growth, calcified cartilage is usually converted to bone as the trabeculae elongate; bone is layed down on the surface of cartilage in the primary spongiosa while almost complete replacement of cartilage occurs in the secondary spongiosa. The enlargement in the middle of the figure is a cross section of cortical bone with Haversian systems where internal remodeling occurs. The enlargement at the lower right shows the different bone cells beginning with inactive lining cells, active osteoblasts (bone‐forming cells), osteocytes (osteoblasts trapped in mineralized matrix) that form an extensive canalicular system throughout the bone, and an active osteoclast (bone‐resorbing cell) forming a Howship's lacuna on the bone surface.



Figure 2.

Digitized fluorescent image of a cross section of bone from the tibia just proximal to the tibiofibular junction. The bone was labeled by injecting fluorescent bone markers at the same concentration (15 mg/kg) at different times during the experiment. The distance between the labeled rings shows the amount of bone growth between injections. The bone section is from a ground control rat for the 9 day Spacelab Life Sciences 1 experiment. Label 1 is a calcein dye injected 12 days before launch, which was about 1 mo before the animal was euthanized. Label 2 is a tetracycline derivative (demeclocycline) given 7 days after the first label to bracket preflight bone formation. Label 3 was injected 4 days after the second label (1.5 days before launch) due to a launch delay. Label 4 (calcein) was given shortly after the shuttle returned from its 9 day mission. The distance from label 4 to the bone surface represents the 9 day period of postrecovery growth. The most rapid growth occurs on the outer surface where muscle is attached.



Figure 3.

The influence of gravity and activity “intensity” on the external forces imposed on the body. On Earth and Mars during quiet standing the gravitational force is supported by body weight, but body weight on Mars is only about 40% of Earth body weight. Inertial forces during running on either Earth or Mars increase peak support force levels to 2–3 times body weight 94. Even so, external and internal musculoskeletal forces generated during running on Mars are only on the same order of magnitude as walking on Earth. Floating in space exerts no external forces on the body.



Figure 4.

The percent change in body constitutents of young rats from 1G values to 0G (Cosmos 1129) or 2G (centrifuge). Data for 0G are from Pitts et al. 196.

Redrawn from Pace et al. 186


Figure 5.

A diagrammatic illustration of the way in which the intestine, kidney, and bone adjust the distribution of calcium to meet the functional demands of reduced, normal, and increased gravitational loads on the skeleton. Reading from the top down and assuming a fixed amount of dietary calcium for all three situations, intestinal absorption is reduced, normal, and enhanced. The increased fecal excretion during immobilization, a model for reduced gravity, is due not only to a decrease in intestinal calcium absorption but also to increased endogenous fecal calcium, the term used for calcium secreted into the lumen of the intestine then lost in epithelial cells and in bile 96. Normal extracellular fluid (ECF) is considered to be quite stable, averaging 2 mg/kg. We are unaware of any data on ECF during exposure to high gravitational loads or exercise. In acute disuse osteoporosis, renal calcium excretion is augmented, a phenomenon referred to as resorptive hypercalciuria, to indicate its association with increased bone resorption and suppression of the parathyroid/1,25‐dihydroxyvitamin D‐axis 233. During exposure to high gravitational loads, renal conservation of calcium through reduced urinary excretion, compared to normal, is not observed. At the whole body level, bone turnover increases with mobilization of mineral from resorption exceeding formation which tends to be depressed only in the unloaded bones. Bone formation is increased in the weight‐bearing regions of the skeleton. The low, normal and increased shading represents the amounts of whole body bone mineral that are the result of these adaptive changes. The sources for the quantitative aspects of adaptation are from the observations in human adults by Heaney 95, Neer et al. 176, LeBlanc and Schneider 134, LeBlanc et al. 135, Silverberg 223, Ragan and Briscoe 201, and in rats by Yeh and Aloia 282,284.



Figure 6.

Sequence of events in the calcium endocrine system that reduces or provides available mineral from intestinal absorption following exposure to low or high gravitational loads on the skeleton. Bone tissue responds to a decrease in gravitational load by the release of calcium ions into the circulation. The increase in serum calcium depresses circulating concentrations of parathyroid hormone which in turn reduces the formation of 1,25‐dihydroxyvitamin D and the intestinal absorption of calcium. Negative calcium balance is augmented by increases in urinary calcium, and in some situations, increases in endogenous fecal calcium (not shown). The response to an increased gravitational load is deposition of calcium in bone that is followed by a change in serum calcium that depends on adequacy of hydration, change in blood pH, and/or level of dietary calcium. Parathyroid hormone and 1,25‐dihydroxyvitamin D may or may not increase, depending on the adequacy of dietary mineral. Intestinal calcium absorption is increased and calcium balances become more positive.



Figure 7.

Hypothetical scheme that shows parallel responses of the calcium endocrine system and the skeleton to spaceflight. Cellular sites of interaction are not detailed. See SUMMARY for further discussion.

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Emily R. Morey‐Holton, Robert T. Whalen, Sara B. Arnaud, Marjolein C. van der Meulen. The Skeleton and its Adaptation to Gravity. Compr Physiol 2011, Supplement 14: Handbook of Physiology, Environmental Physiology: 691-719. First published in print 1996. doi: 10.1002/cphy.cp040131