During the past two years, orthopaedic researchers have had a unique opportunity to study the impact of microgravity, such as that experienced during spaceflight, on musculoskeletal tissues. Over the course of three space shuttle missions, a NASA mouse-tissue Biospecimen Sharing Program looked at the effects of spaceflight not only on bone and muscle but also on cartilage and tendon.

Three investigators involved in the program—Stavros Thomopoulos, PhD, of Washington University in St. Louis; Jeffrey C. Lotz, PhD, of the University of California, San Francisco; and Eduardo Almeida, PhD, of the National Aeronautics and Space Administration (NASA)—presented “New Insights into the Effects of Spaceflight in Musculoskeletal Tissues” during the 2012 annual meeting of the Orthopaedic Research Society (ORS).

“This is the dream of every animal studies committee,” noted Dr. Thomopoulos, whose studies focused on the rotator cuff. “It was probably the best utilization of animals that I’ve ever seen. The animals were dissected and every tissue was passed on to a different researcher for a specific study.”

Tendon diameters decrease
“Unlike the joints in the hip, the shoulder is inherently unstable,” explained Dr. Thomopoulos, “because you have a relatively large ball that fits into a much smaller socket. To prevent frequent dislocations, dynamic forces are needed to hold the humeral head up against the glenoid. The stability and motion of the joint depends on the rotator cuff muscles and a firm attachment through the tendon onto the bone of the humeral head.”

Rotator cuff degeneration is a major clinical issue, affecting a large percentage of the population and frequently leading to significant pain and loss of function. In addition, if the rotator cuff tears, the healing potential and functional outcomes—even after surgery—can be poor in many cases. All of these tissues are sensitive to their loading environment, and long-duration spaceflight, he pointed out, with significant periods of unloading, could lead to deterioration of the tissues, potential degradation, loss of function, and tears that would require surgical intervention.

Dr. Thomopoulos looked at atrophy of the infraspinatus and supraspinatus muscles; fibrosis, which would lead to decreased capacity of the muscle; and the accumulation of fatty tissue, which is a hallmark of rotator cuff disease. His research also focused on the mechanics, matrix degradation, and matrix synthesis in the supraspinatus and infraspinatus tendons, as well as the degree of bone formation and resorption, as measured by genetic markers.

“We hypothesized that in these mice, under microgravity conditions, the rotator cuff would degenerate, with decreases in muscle mass, increases in adipogenesis or the development of fatty tissue, and increases in fibrosis. For the tendon and its insertion into bone, we expected an increase in degradation of matrix and a decrease in matrix synthesis. For the bone, we expected increased bone resorption and decreased bone formation.”

Some of the results were surprising. For example, muscle and bone mass did decrease, but although the tendons shrank in diameter, their structural properties did not change. This meant that tendon material properties actually increased under microgravity.

“The data are still preliminary,” he concluded, “but we are continuing to explore the pathways that result in these changes. Hopefully, we will have an opportunity to do a longer joint mission with Russia.”

Astronauts with aching backs
“Back pain is of real significance to NASA for a very practical reason,” said Dr. Lotz. “The incidence of back pain in space is significant; more than half of all astronauts report back pain during spaceflight and more than a quarter say it is ‘moderate to severe.’” In addition, once they return to earth, astronauts have an increased risk of incurring a disk herniation. His research focused on altered biomechanics of the spine, in particularly on the intervertebral disks.

Disk function—both in gravity and microgravity—has several aspects. The center of the disk is an osmotic pump, attracting and emitting fluids. Fluids from blood vessels and bone inflates the disk, creating tension, and giving the spine its mechanical stability. Additionally, because the disk itself has no blood vessels, it must get its nutrition from the surrounding bone.

This permeability between the disk nucleus and the adjacent bone is important for transport, but it can also allow fluids to leave the disk. The result is a dynamic relationship among load, hydration, and disk height. The impact of microgravity on this exchange might be one reason that astronauts experience back pain.

On earth, loads placed on the spine during the day force fluids out. At night, the fluid is replenished, stiffening the spine and increasing disk height. In space, with less loading, less fluid is forced out and the spines of astronauts change both their height and shape, becoming longer and straighter. This loss of lordosis, if it results in exceeding normal range of motion, could damage tissue and alter the behavior of cells.

“In addition to this, an active stiffness from tissues and muscles is at work that helps keep us upright,” explained Dr. Lotz. “Our trunk mass wants to tip us one way, and then passive tissues, ligaments, tendons, and muscles, tend to keep us up. This dynamic balance is critical in the lower lumbar spine.”

Researchers hypothesized that both biologic and biomechanical homeostases have evolved in gravity conditions and are disturbed during space flight. Surrogate experiments on earth have supported this theory. Photos of Russian astronauts who have spent nearly 4 months in space show how the spine lengthens and straightens, losing both kyphosis and lordosis as a result of the combination of loss of muscle tone and increasing pressure in the disk.

“If the interplay of passive and active tissues around the spine is disturbed,” noted Dr. Lotz, “tissues become damaged, basically by exceeding the range of motion of passive tissues because the active tissues aren’t participating.”

The geometry of bone
According to Dr. Almeida, microgravity changes both the volume and thickness of bone. Working with the pelvic bones of mice, he focused on the impact of microgravity on the cellular pathways involved in bone loss.

“We think that the mechanical stimulus of gravity is important to keep tissue regeneration at a normal rate; in microgravity, tissue regenerative deficits may be one explanation for the long-term loss of loss of bone, muscle, and other tissues,” he said. “Microgravity may be inhibiting the process by which a variety of stem cells go on to regenerate tissues.” His research looked at bone and bone marrow, analyzing both cellular and gene expression components to see whether this hypothesis worked.

The volume of bone in the pelvic bones of mice that spent 2 weeks in space decreased by 6 percent; the bone thickness decreased by 12 percent and the ischium itself changed shape, straightening from a 159-degree angle to a 166-degree angle. The marrow cavity became enlarged, consistent with the loss of trabecular bridges between the two sides of bone.

“Recently, more importance has been given to the role of osteocytes in bone degradation,” said Dr. Almeida. “All it takes is a small degradation of the surface of lacunae for a lot of calcium to be released; we wanted to know whether spaceflight induced osteocytic osteolysis. We think that in space, we have both the conventional degradation of bone by osteoclasts and this process of osteocytic osteolysis.”

If this is true, long-term spaceflight could result in considerable tissue breakdown, because cells may be regenerated at a slower pace than they degenerate. Cell growth continues, but may not be adequate to replace the lost cells. “Long-term biological experiments in microgravity on the International Space Station are needed to resolve these questions,” he concluded.

Drs. Thomopoulos and Almeida report no conflicts. Dr. Lotz reports ties to ISTO Technologies; Nocimed; Spinal Motion; Simperica; Spinal Restoration; Relievant; DePuy, A Johnson & Johnson Company; Orthofix, Inc.; Spine; The Spine Journal. Research funding was provided by NASA.

Mary Ann Porucznik is managing editor of AAOS Now. She can be reached at porucznik@aaos.org