Innovative Compound Offers Solution for Mitigating Astronaut Bone Degradation

A recently published study indicates that a specially formulated compound administered to mice on the International Space Station (ISS) effectively counteracted bone loss typically incurred during space travel. This groundbreaking discovery not only has implications for astronauts subjected to extended periods of microgravity but also offers therapeutic possibilities for osteoporosis patients on Earth.

The study, which was released today (September 18) in the Nature Partner Journal, npj Microgravity, demonstrates that a bioengineered compound given to mice in space significantly curtailed the bone loss generally associated with prolonged periods in a microgravity environment. The research was spearheaded by a multidisciplinary group of experts from the University of California at Los Angeles (UCLA) and the Forsyth Institute in Cambridge, Massachusetts. The findings illuminate a viable treatment option for extreme bone loss resulting from extended space missions, as well as for degenerative musculoskeletal conditions on Earth.

The Ramifications of Microgravity on Skeletal Health

The issue of bone loss due to microgravity has been a longstanding concern for extended space missions. In the absence of gravitational force, bone loss occurs at a rate 12 times faster than on Earth. Astronauts in low Earth orbit can suffer up to 1% bone loss per month, compromising their skeletal health and elevating the risk of fractures during long-term space travel and later in life.

Existing Remedies and Their Shortcomings

Current approaches to mitigating bone loss focus on mechanical loading through exercise to stimulate bone growth. However, this is far from ideal for crew members who spend up to six months in space. Exercise is not always effective in preventing bone loss, consumes substantial time, and may be unsuitable for particular injuries.

The study examined whether the systemic introduction of NELL-like molecule-1 (NELL-1) could ameliorate bone loss induced by microgravity. Chia Soo, MD, who serves as the vice chair for research in the Division of Plastic and Reconstructive Surgery and professor in the Departments of Surgery and Orthopaedic Surgery at UCLA’s David Geffen School of Medicine, led the study. NELL-1, discovered by Kang Ting, DMD, DMSc at the Forsyth Institute, is essential for bone formation and maintenance of bone density. Professor Ting has also conducted multiple studies demonstrating that localized administration of NELL-1 can regenerate musculoskeletal tissues such as bone and cartilage.

Sophisticated Drug Delivery Methods

For the systemic introduction of NELL-1 in space, the research team needed to minimize the frequency of injections. Researchers Ben Wu, DDS, PhD, and Yulong Zhang, PhD at the Forsyth Institute extended the half-life of NELL-1 from 5.5 hours to 15.5 hours without compromising its bioactivity. They also bioconjugated an inert bisphosphonate to create a specialized BP-NELL-PEG molecule that more specifically targets bone tissues, devoid of the harmful effects usually associated with bisphosphonates.

The altered molecule underwent thorough assessment by the teams of Soo and Ting to ascertain its efficacy and safety on Earth. They concluded that BP-NELL-PEG showed elevated specificity for bone tissue without triggering discernible adverse effects.

Findings and Practical Implications

In collaboration with the Center for the Advancement of Science in Space (CASIS) and NASA Ames, the research team prepared rigorously for the SpaceX CRS-11 mission to the ISS. Both the mice on the ISS and those that remained at the Kennedy Space Center as Earth gravity controls exhibited a substantial increase in bone formation when treated with BP-NELL-PEG, with no observable adverse health effects.

Final Observations and Prospective Developments

Lead corresponding author Chia Soo stated, “Our results offer significant promise for extended space missions involving prolonged exposure to microgravity.” Co-principal investigator Kang Ting added that if validated by human trials, BP-NELL-PEG could serve as an effective treatment for bone loss and musculoskeletal degeneration where conventional resistance training is impractical due to injury or other limiting factors. Ben Wu, another co-principal investigator, noted that this bioengineering strategy could also offer vital benefits for treating extreme osteoporosis and related conditions on Earth.

The study is supported by grants from CASIS and the National Institutes of Health. Additional financial backing and support come from various departments at UCLA, the American Association of Orthodontists Foundation, and the International Orthodontics Foundation. Pin Ha, MD, DDS, MS, who is overseeing the analysis of the live animal return data, expressed hope that the findings would offer valuable insights for helping astronauts recover from longer space missions.

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

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More about Innovative Compound for Astronaut Bone Loss

• npj Microgravity Journal
• University of California at Los Angeles (UCLA) Research
• Forsyth Institute Research
• Center for the Advancement of Science in Space (CASIS)
• National Institutes of Health (NIH) Grants
• SpaceX CRS-11 Mission Details
• NASA’s Research on Microgravity and Bone Loss
• Osteoporosis: An Overview
• DOI Link to the Study
• American Association of Orthodontists Foundation
• International Orthodontics Foundation