Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice
Open accessAbstract
Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF). 64-day-old female C57BL/6J mice (n=12/group) were injected subcutaneously with OPG-Fc (20mg/kg) or an inert vehicle (VEH), 24h prior to launch. Ground control (GC) mice (VEH or OPG-Fc) were maintained under environmental conditions that mimicked those in the space shuttle middeck. Age-matched baseline (BL) controls were sacrificed at launch. GC/VEH, but not SF/VEH mice, gained tibia BMD and trabecular volume fraction (BV/TV) during the mission (P<0.05 vs. BL). SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had greater BV/TV than SF/VEH or GC/VEH. SF reduced femur elastic and maximum strength in VEH mice, with OPG-Fc increasing elastic strength in SF mice. Serum TRAP5b was elevated in SF/VEH mice vs. GC/VEH mice. Conversely, SF/OPG-Fc mice had lower TRAP5b levels, suggesting that OPG-Fc preserved bone during spaceflight via inhibition of osteoclast-mediated bone resorption. Decreased bone formation also contributed to the observed osteopenia, based on the reduced femur periosteal bone formation rate and serum osteocalcin level. Overall, these observations suggest that the beneficial effects of OPG-Fc during SF are primarily due to dramatic and sustained suppression of bone resorption. In growing mice, this effect appears to compensate for the SF-related inhibition of bone formation, while preventing any SF-related increase in bone resorption. We have demonstrated that the young mouse is an appropriate new model for SF-induced osteopenia, and that a single pre-flight treatment with OPG-Fc can effectively prevent the deleterious effects of SF on mouse bone.
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Osteoprotegerin-Fc given subcutaneously to mice flown for 12 days in space produced a sustained suppression of bone resorption.
“Osteoprotegerin-Fc given subcutaneously to mice flown for 12 days in space produced a sustained suppression of bone resorption”
From Osteoclasts and Microgravity (2020) · cites this paper as [77]
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- Authors
- Lloyd, S. A., Morony, S. E., Ferguson, V. L., Simske, S. J., Stodieck, L. S., Warmington, K. S., Livingston, E. W., Lacey, D. L., Kostenuik, P. J., & Bateman, T. A.
- Affiliations
- Pennsylvania State University (US)
- Amgen (United States) (US)
- University of Colorado Boulder (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Bateman, Ted A.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 81
- Pages
- 562-572
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- PMC
- PMC7937349
- OpenAlex
- W2145689197
- Cited by
- 68
- References
- 44
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 13 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Space Biomedical Research Institute (BL01302)
- NIH (5 R01 AR059221-02)
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteoprotegerin, RANKL inhibitor, microgravity, osteopenia, bone resorption, osteoclasts, bone formation, trabecular bone volume, bone strength, TRACP-5b, osteocalcin
- MeSH terms
- Alkaline Phosphatase, Animals, Biomechanical Phenomena, Bone Resorption, Disease Models, Animal, Female, Immunoglobulin Fc Fragments, Mice, Inbred C57BL, Recombinant Fusion Proteins, Space Flight, Weightlessness, Biomarkers, Bone Density, Osteocalcin, Bone Density Conservation Agents, Mice, Osteoprotegerin, RANK Ligand
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