Space-Age Solution: Preventing Astronaut Bone Loss With Innovative Compound

New Research showcased the efficacy of an engineered compound in preventing bone loss in space-traveling mice. This breakthrough may offer solutions for astronauts and osteoporosis patients on Earth.

A new study published today (September 18) in a Nature Partner Journal, npj Microgravity, finds an engineered compound given to mice aboard the International Space StationThe International Space Station (ISS) is a large spacecraft in orbit around the Earth that serves as a research laboratory and spaceport for international collaboration in space exploration. It was launched in 1998 and has been continuously occupied by rotating crews of astronauts and cosmonauts from around the world since 2000. The ISS is a joint project of five space agencies: NASA (USA), Roscosmos (Russia), JAXA (Japan), ESA (Europe), and CSA (Canada). It orbits the Earth at an altitude of approximately 400 kilometers (250 miles), and provides a unique platform for scientific research, technological development, and human space exploration.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>International Space Station (ISS) largely prevented the bone loss associated with time spent in space. The study, led by a transdisciplinary team of professors at the University of California at Los Angeles (UCLA) and the Forsyth Institute in Cambridge, Massachusetts, highlights a promising therapy to mitigate extreme bone loss from long-duration space travel as well as musculoskeletal degeneration on Earth.

Microgravity’s Impact on Bones

Microgravity-induced bone loss has long been a crucial concern for long-term space missions. Decreased mechanical loading due to microgravity induces bone loss at a rate 12-times greater than on Earth. Astronauts in low Earth orbit may experience bone loss up to 1% per month, endangering astronaut skeletal health and increasing the risk of fractures during long-duration spaceflight and later in life.

Current Solutions and Their Limitations

Currently, the mitigation strategy for bone loss relies on exercise-induced mechanical loading to promote bone formation but is far from perfect for crewmembers spending up to six months in microgravity. Exercise does not always prevent bone loss, takes up valuable crew time, and may be contraindicated for certain types of injuries.

The new study investigated whether systemic delivery of NELL-like molecule-1 (NELL-1) can reduce microgravity-induced bone loss. It was led by Chia Soo, MD, vice chair for research in the Division of Plastic and Reconstructive Surgery, professor in Departments of Surgery and Orthopaedic Surgery at UCLAThe University of California, Los Angeles (UCLA) is a public land-grant research university in Los Angeles, California. It is organized into the College of Letters and Science and 12 professional schools. It is considered one of the country's Public Ivies, and is frequently ranked among the best universities in the world by major college and university rankings.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>UCLA David Geffen School of Medicine. NELL-1, which was discovered by Kang Ting, DMD, DMSc at the Forsyth Institute, is crucial for bone development and bone density maintenance. Professor Ting also led numerous studies to show that local delivery of NELL-1 can regenerate musculoskeletal tissues such as bone and cartilage.

Advanced Delivery Techniques

Systemic delivery of NELL-1 aboard the ISS requires the team to minimize the number of injections. Ben Wu, DDS, PhD and Yulong Zhang, PhD at the Forsyth Institute enhanced NELL-1’s therapeutic potential by extending the molecule’s half-life from 5.5 hours to 15.5 hours without losing bioactivity, and bioconjugated an inert bisphosphonate (BP) to create a “smart” BP-NELL-PEG molecule that more specifically targets bone tissues without the common deleterious effects of BP.

The modified molecule was then extensively assessed by the Soo and Ting teams to determine the efficacy and safety of BP-NELL-PEG on earth. They found that BP-NELL-PEG displayed superior specificity for bone tissue without causing observable adverse effects.

Results and Practical Applications

To ascertain the practical applicability of BP-NELL-PEG in real space conditions, the researchers worked with Center for the Advancement of Science in Space (CASIS) and National Aeronautics and Space Administration (NASAEstablished in 1958, the National Aeronautics and Space Administration (NASA) is an independent agency of the United States Federal Government that succeeded the National Advisory Committee for Aeronautics (NACA). It is responsible for the civilian space program, as well as aeronautics and aerospace research. Its vision is "To discover and expand knowledge for the benefit of humanity." Its core values are "safety, integrity, teamwork, excellence, and inclusion." NASA conducts research, develops technology and launches missions to explore and study Earth, the solar system, and the universe beyond. It also works to advance the state of knowledge in a wide range of scientific fields, including Earth and space science, planetary science, astrophysics, and heliophysics, and it collaborates with private companies and international partners to achieve its goals.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>NASA) Ames to prepare extensively for the SpaceXCommonly known as SpaceX, Space Exploration Technologies Corp. is a private American aerospace manufacturer and space transport services company that was founded by Elon Musk in 2002. Headquartered in Hawthorne, California, the company designs, manufactures, and launches advanced rockets and spacecraft. SpaceX's ultimate goal is to reduce space transportation costs and enable the colonization of Mars.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>SpaceX CRS-11 mission to the ISS, where astronauts Peggy Whitson, PhD and Jack D. Fisher, MS carried out the studies.   Half of the ISS mice were exposed to microgravity (“TERM Flight”) for a lengthy 9-week period to simulate the challenges of long-duration space travel, while the remaining mice were flown back to Earth at 4.5 weeks post-launch, for the first ever live animal return (“LAR Flight”) of mice in US history. Both TERM and LAR Flight groups were treated with either BP-NELL-PEG or phosphate buffered saline (PBS) control. An equivalent cohort of mice remained at the Kennedy Space Center and were treated similarly with BP-NELL-PEG or PBS to serve as normal Earth gravity (“Ground”) controls.

Both Flight and Ground mice treated with BP-NELL-PEG exhibited a significant increase in bone formation. The treated mice in space and on Earth displayed no apparent adverse health effects.

Conclusions and Future Directions

“Our findings hold tremendous promise for the future of space exploration, particularly for missions involving extended stays in microgravity,” said lead corresponding author Chia Soo. “If human studies bear this out, BP-NELL-PEG could be a promising tool to combat bone loss and musculoskeletal deterioration, especially when conventional resistance training is not feasible due to injuries or other incapacitating factors,” said co-co-principal investigator, Kang Ting.

“This bioengineering strategy can also have important benefits on Earth, offering a potential therapy for patients suffering from extreme osteoporosis and other bone-related conditions,” said co-co-principal investigator, Ben Wu.

“As the next step, UCLA project scientist, Pin Ha, MD, DDS, MS, is overseeing analysis of the live animal return data. We hope this will provide some insight on how to help future astronauts recover from longer-duration space missions,” said Chia Soo.

Reference: “Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice” 18 September 2023, npj Microgravity.
DOI: 10.1038/s41526-023-00319-7

The research is supported by grants from CASIS and National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>National Institutes of Health. Additional funding and support are provided by UCLA Division of Plastic and Reconstructive surgery, UCLA Department of Surgery, UCLA Department of Orthopaedic Surgery and the UCLA Orthopaedic Hospital Research Center, the American Association of Orthodontists Foundation, and the International Orthodontics Foundation. Pin Ha and Yulong Zhang, and associate professor Jin Hee Kwak, DDS, are co-first authors and contributed equally to this project.