The temporal response of bone to unloading.
Open accessAbstract
A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with 45Ca and [3H]proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more 45Ca and [3H]proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading. We believe that this cycle of inhibition and resumption of bone formation has profound implications for understanding bone dynamics during space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.
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Skeletal unloading suppresses bone formation and increases osteocyte apoptosis.
“Skeletal unloading also suppresses bone formation (277, 278) and increases osteocyte apoptosis (121).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [278]
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- Authors
- GLOBUS, R. K., BIKLE, D. D., & MOREY-HOLTON, E.
- Affiliations
- Ames Research Center (US)
- ORCID
- BIKLE, DANIEL D.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1986-02
- Volume
- 118
- Issue
- 2
- Pages
- 733-742
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2091643005
- Cited by
- 219
- References
- 19
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 1 · 2013: 3 · 2012: 7
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- NASA STI Repository (National Aeronautics and Space Administration) (submittedVersion)
- Funders
- National Aeronautics and Space Administration
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- skeletal unloading, hindlimb unloading, simulated microgravity, bone formation, bone resorption, bone growth, bone remodeling, lumbar vertebrae, trabecular bone, cortical bone, spaceflight, immobilization, tetracycline labeling, histomorphometry, calcium incorporation, proline incorporation, growing rats
- MeSH terms
- Animals, Bone and Bones, Bone Development, Bone Matrix, Calcium, Calcium Radioisotopes, Hindlimb, Kinetics, Lumbar Vertebrae, Male, Organ Size, Proline, Rats, Inbred Strains, Space Flight, Tetracycline, Tibia, Weightlessness, Rats
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