Bone Lost in Space

Sunday, June 26, 2016

NASA study could aid osteoporosis treatments on Earth

July 18, 2016

The skeleton you have today is not the same skeleton you had 10 years ago. “Bone is a tissue that is constantly remodeling,” explains D. Rick Sumner, PhD, chairperson of Rush’s Department of Anatomy and Cell Biology. “You essentially get a new skeleton every six to 10 years.”

The thought of bone as a living, continually changing tissue may seem counterintuitive, given that the skeleton is so hard and strong, Sumner acknowledges. From an engineering perspective, though, the skeleton’s ability to repair itself is vital.

“Bone is a load-bearing structure, and any load-bearing structure is going to accumulate damage over time,” Sumner says. “If enough damage accumulates and it doesn’t get repaired, the structure will break.” 

‘Use it or lose it’

Sumner and other researchers have learned a great deal in recent decades about how bone remodels and repairs itself. This type of basic science research has the potential to revolutionize the treatment of osteoporosis, a disease that weakens bones.

Scientists have already identified one bone protein, called sclerostin, which suppresses bone formation, leading in turn to the development of antibodies that block sclerostin and a drug using those antibodies to reduce spine fracture risk. Sumner is involved in a new study funded by NASA that may help identify additional molecular targets for osteoporosis drugs, while furthering knowledge of sclerostin.

Astronauts in space face similar bone loss as people with osteoporosis — but at an accelerated rate. The bones of astronauts weaken when they spend time in space due to the “use it or lose it” phenomenon, Sumner says.

Bones renew when stressed by the challenge of bearing a person’s weight. When there’s no gravity, as in space, the skeleton is no longer bearing weight, and bone stops replenishing. As NASA gears up for an eventual Mars mission, the agency is looking for groundbreaking ways to counteract bone loss during the lengthy commute.

The boss of bone metabolism

The NASA study is focusing on a specific type of bone cell called osteocytes, which operate somewhat like supervisors at a construction site — as if a construction crew were rebuilding a skeleton.

On the construction team are two other bone cells: osteoclasts and osteoblasts. Osteoclasts excavate and resorb bone, while osteoblasts fill in the resulting holes with new tissue. Sumner compares it to the upkeep that goes on in a parking garage. “A jackhammer is used to take out some of the cement, and then more cement is put back in,” he says.  “The amazing thing about the skeleton is that this remodeling occurs constantly, without any interruption of function, unlike the parking garage, where whole sections have to be roped off.”

Like a supervisor, osteocyte cells direct and manage the construction work by exchanging key information with the worker cells. Scientists have had trouble studying osteocytes because they are encased  in small interconnected caves buried in the bone matrix. However, with modern-day technology and methods, researchers now understand how important the osteocytes are to bone remodeling and to the cellular communication that occurs inside and outside bone tissue.   

Osteocytes secrete molecular signals, such as the protein sclerostin, that tell other cells to start or stop a particular activity such as forming bone matrix. These boss cells ensure the right counterbalance between too much and too little bone being produced.

Hope for osteoporosis — and space travelers

The NASA study intends to identify changes that occur in the activity of osteocyte cells during space flights. It will try to determine which genes inside osteocytes get turned on or off when there’s no gravity, thus secreting more or less of a protein. It also will explore how  these molecular changes are  linked to decreases in bone density and strength.

Scientists will study mice after they spend months on the International Space Station to see if their osteocyte cells are producing more or less of the genetic instructions, called RNA, that direct cells to create certain proteins, as compared to mice that spend the same amount of time on Earth. Identifying the molecular basis of bone loss in space is the first step in identifying potential treatments for both astronauts and people with earth-bound osteoporosis. 

The NASA bone study, which is still in the planning stages, is led by Indiana University’s Alexander Robling, PhD, associate professor of anatomy and cell biology. In addition to enlisting Sumner and other Rush researchers, the study involves scientists from Baylor College of Medicine, Baylor College of Dentistry, and the National Center of Biotechnology in Spain. 

Sumner’s lab — which is equipped with advanced imaging capabilities that allow for studying bone matrix composition — will be in charge of taking measurements of the bone matrix and detailing the chemical composition and distribution of mineral in the bones of the mice subjects. Sumner and Ryan Ross, PhD, assistant professor in anatomy and cell biology at Rush, will use two advanced techniques — backscatter scanning electron microscopy and Fourier transform infrared spectroscopy — to create a detailed map of the bone and uncover specific chemical changes.

“We’ll be able to look in the immediate vicinity of the little holes where the osteocytes live,” Sumner says. “We can also see if they are altering their surrounding neighborhoods.”   

In addition to participating in this NASA study, Sumner is involved in NASA’s Human Research Program, serving as an expert member of the Bone and Muscle Risk Standing Review Panel. In this role, Sumner reviews current research on the effects of space travel on bone and muscle and helps NASA identify knowledge gaps that remain. 

As a child of the Space Age, Sumner is thrilled to be involved with NASA. “I can remember in 1969, when they landed on the moon,” he says. “We watched it on TV. I was 15 years old. The world was captivated. 

“A great outcome from our study would be the identification of novel ways to help astronauts avoid bone loss that will also be beneficial for the rest of us earthlings.”

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