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Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats.
Open accessAbstract
To clarify how the changes in bone formation and resorption affect bone volume and strength after mechanical unloading, the effect of inhibition of bone resorption by a potent bisphosphonate, pamidronate, on bone mineral density (BMD), histology, and strength of hind limb bones was examined using tail-suspended growing rats. Tail suspension for 14 days reduced the gain in the BMD of the femur at both the metaphysis rich in trabecular bone and the diaphysis rich in cortical bone. Treatment with pamidronate increased the total BMD as well as that of the metaphysis of the femur but had almost no effect on the BMD of the diaphysis in both control and tail-suspended rats. Histological examinations revealed that 14-day tail suspension caused a loss of secondary cancellous bone with a reduction in the trabecular number and thickness in comparison with control rats. In the femoral diaphysis, the diameter and cortical bone thickness increased to a lesser degree in tail-suspended rats when compared with rats without tail suspension, and a marked reduction in bone formation and the layers of alkaline phosphatase–positive cells was observed at the periosteal side. Pamidronate treatment increased secondary cancellous bone but could not restore normal growth-induced periosteal bone apposition and bone strength. Because the material strength of the femoral diaphysis at the tissue level was not affected by pamidronate treatment, the inability of pamidronate to prevent the reduction in physical strength of the femoral diaphysis does not appear to be due to a change in the quality of newly formed bone. These results demonstrate that tail suspension reduces the growth-induced periosteal modelling drift and that the antiresorptive agent pamidronate is unable to restore normal periosteal bone apposition.
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Bisphosphonates are frequently ineffective at improving cortical bone strength in rat unloading models, even when cancellous bone strength is significantly improved.
“bisphosphonates are frequently ineffective at improving cortical bone strength in rat unloading models (284 -286), even when cancellous bone strength was significantly improved (286).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [284]
OPG significantly increased density and strength of cortical bone in a rat unloading model nearly identical to one where bisphosphonate had no such effects.
“OPG significantly increased the density and strength of cortical bone (298) in a rat unloading model that was nearly identical in design to one where bisphosphonate treatment had no such effects (284).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [284]
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Metadata
- Authors
- Kodama, Y., Nakayama, K., Fuse, H., Fukumoto, S., Kawahara, H., Takahashi, H., Kurokawa, T., Sekiguchi, C., Nakamura, T., & Matsumoto, T.
- Affiliations
- The University of Tokyo (JP)
- Teikoku Hormone Manufacturing Co., Kawasaki, Kanagawa, Japan
- National Space Development Agency of Japan, Tsukuba, Ibaraki, Japan
- Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
- Tokushima University (JP)
- Corresponding author
- Matsumoto, Toshio
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-07-01
- Volume
- 12
- Issue
- 7
- Pages
- 1058-1067
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W1983023085
- Cited by
- 76
- References
- 28
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › 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
- pamidronate, bisphosphonates, bone resorption inhibition, tail suspension test, mechanical unloading, cortical bone mass, bone strength, bone mineral density, trabecular bone, bone formation, femoral diaphysis, femoral metaphysis, growing rats
- MeSH terms
- Pamidronate, Amino Acids, Animals, Biomechanical Phenomena, Bone Resorption, Diphosphonates, Femur, Male, Stress, Mechanical, Tibia, Bone Density, Rats, Sprague-Dawley, Weightlessness Simulation, Rats
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