Fact sheet number: FS-2001-11-193-MSFC
Osteoporosis is a debilitating disease that can lead to bone fractures and result in reduced quality of life for the elderly population it generally afflicts. With 80 percent of the incidence of osteoporosis in females, more than 30 million women in America are at risk of developing osteoporosis and subsequently have an increased risk of serious bone fractures.
Half the women in America over 50 may eventually suffer fractures stemming from this bone loss. As a consequence of complications from the severe fractures, 25,000 Americans die from this disease each year.
A potential treatment for this brittle bone condition is being tested on NASA's Space Shuttle by Amgen Inc., a large biotechnology firm in Thousand Oaks, Calif. This treatment is the protein osteoprotegerin (OPG), a potent regulator of bone metabolism. The experiment is made possible by Amgen's work with one of NASA's 17 Commercial Space Centers: BioServe Space Technologies at the University of Colorado, Boulder, and Kansas State University, Manhattan.
Scientists are using weightlessness -- the microgravity environment created by the Shuttle orbiting Earth -- to simulate accelerated bone loss. One of the physiological changes experienced by astronauts during space flight is loss of bone mass, similar to osteoporosis experienced by millions of elderly women here on Earth. The removal of gravitational loading on the skeleton in space is generally responsible for this accelerated bone loss in astronauts. Human life sciences experiments on the International Space Station are studying this bone loss and evaluating possible treatments (countermeasures) for reducing bone loss during space flight.
The Commercial Biomedical Testing Module experiment will be conducted over 11 days on the Space Shuttle Endeavour, STS-108 mission, set for launch in late November. The Shuttle will be docked with the International Space Station during this mission.
In the mid 1990s, Amgen scientists discovered OPG as part of the company's genomic drug discovery program and characterized its role as a key protein in bone cell communications. These bone cells regulate the two most fundamental aspects of bone health: the removal of old, damaged bone (osteoclasts) and the formation of new, strong bone (osteoblasts). One mechanism that contributes to osteoporosis here on Earth and the bone loss experienced by astronauts is that the osteoclasts can remove too much (often healthy) bone.
Amgen discovered that OPG binds with another protein, OPG-ligand (also known as OPGL and RANKL), and by doing so, prevents osteoclasts from removing too much bone. Amgen is developing a form of OPG to treat diseases associated with bone loss.
This commercial space experiment augments Amgen's prior ground-based pre-clinical research with BioServe, which examined the efficacy of OPG using ground-based disuse (unloading) models for osteoporosis. These studies demonstrated the potential of OPG to mitigate the bone loss associated with the removal of gravitational loading, leading to this space flight experiment, in which a more complete, systematic unloading is expected.
Results of Amgen's research in this area have been published in many journals, including Nature, Endocrinology, Bone, the Journal of Bone and Mineral Research, the Journal of Orthopedic Research, and Genes and Development, and have been featured in Science News.
Amgen has completed Food and Drug Administration (FDA) Phase 1 clinical trials on OPG in humans, with the next step being FDA Phase 2 human clinical trials. Through these trials, Amgen is evaluating the safety and effectiveness of using OPG to treat osteoporosis and bone loss associated with metastatic bone cancer. This space experiment provides another preclinical model for determining the effectiveness of OPG to treat bone loss.
In the environment of space where there are limited weight-bearing experiences, the messages received by the osteoblasts and osteoclasts are altered. Specifically, without the stresses and strains caused by gravitational loading, osteoclasts remove more bone and osteoblasts deposit less new bone. To examine in more detail how these signals change and how OPG mitigates these changes, Amgen is using laboratory mice as test subjects.
Just before launch, Amgen scientists will treat 12 laboratory mice, bred specifically for laboratory research, with OPG; 12 similar laboratory mice will receive a placebo. During the flight, the rodents will reside in an Animal Enclosure Module - an animal habitat that has been used on numerous missions and was designed especially for space flight by NASA's Ames Research Center in Moffett Field, Calif. Similarly treated mice will remain on Earth to control for the effects of gravity. The habitat automatically provides food and water for the mice. Periodically, crew members will monitor the status of the mice and their habitat.
Immediately after the Shuttle lands, the mice will be returned to Amgen and BioServe scientists, who will examine the effects of space flight and the ability of OPG to mitigate the effects of space flight on osteoclast/osteoblast signaling via cellular histology, X-ray and computed tomography (CT) imaging and changes in gene expression and other analysis methods.
This is the first time OPG will be studied in space and is Amgen's first space experiment. Since discovering OPG's role in osteoporosis in the mid 1990s, Amgen has done extensive ground-based, preclinical research with this protein.
The habitat, designed by NASA's Ames Research Center, has provided a safe environment for flying laboratory animals on several Shuttle missions.
The Commercial Biomedical Testing Module experiment is a commercial payload sponsored by NASA's Space Product Development Program at the Marshall Space Flight Center in Huntsville, Ala. Through 17 NASA Commercial Space Centers - specializing in everything from combustion to agriculture to biotechnology -- this program assists companies developing microgravity-related experiments and helps them explore how space research can contribute to the growth of their businesses.
Industry funds the research, pays for a portion of launch costs, and brings resulting products or services to market. Because a company pays for the research, it has the opportunity to commercialize products that may be developed as a result of the research.
BioServe Space Technologies is a NASA Commercial Space Center jointly located with the Aerospace Engineering Sciences Department at the University of Colorado in Boulder and the Division of Biology at Kansas State University in Manhattan. Since 1991, BioServe has flown a variety of payloads in space on 19 missions - 16 Shuttle flights, twice onboard the Russian space station Mir and once on the International Space Station - for a cumulative total of 510 days in orbit. A summary of BioServe's flight history can be viewed at:
This space experiment will contribute to Amgen's ground-based studies of OPG. Since space flight induces a complete, more systematic, accelerated bone loss, it is expected to provide a good model for osteoporosis and potential treatments. Potentially, it could provide scientists with further insight into the relationship between skeletal loss from microgravity and the role of OPG and OPGL in the determination of bone composition, morphology and mechanical properties. This data may assist Amgen in its development of OPG as a treatment for osteoporosis.
NASA also is interested in treatments that prevent bone loss in astronauts. Microgravity-induced bone loss is a significant barrier for long-term human space flight. For various reasons, current medications for osteoporosis are not appropriate or ideal countermeasures for most astronauts. In addition to this study, NASA is studying bone loss in Space Station crew members.
Additional information about Expedition Four and this experiment can be found at: