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Cited by 56Bone health and osteoporosis researchBone Metabolism and DiseasesBone health and treatments

High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse.

Yang Li, Chao, Majeska, Robert J., Laudier, Damien M., Mann, Richard, Schaffler, Mitchell B.·2005·Bone
DOI 10.1016/j.bone.2005.04.041
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Abstract

Disuse induces rapid and severe bone loss in larger mammals as a result of greatly elevated osteoclastic resorption. In this study, we tested whether risedronate (RIS), a potent inhibitor of osteoclastic activity, would effectively prevent cancellous bone loss in female beagles (5-7 years old, N = 28) subjected to single forelimb immobilization (IM) for 12 months. Age-matched, non-IM dogs served as controls (Con). Half the animals from each group received RIS 1 mg/kg p.o. daily (Con + RIS, IM + RIS). Remaining dogs received sterile water (Con, IM). Histomorphometry showed that IM caused a dramatic reduction in cancellous bone mass (-71%) of distal 2nd metacarpals, characterized by marked decreases in trabecular width (-51%) and number (-41%), and 4-fold increases in the indices of bone resorption (eroded surface, osteoclast number, and surface). Bone formation indices (calcein-labeled surface, osteoid surface, and bone formation rate) were also significantly higher in IM than in controls. Activation frequency in IM increased about 4-fold beyond control level. RIS treatment reduced, but did not abolish cancellous bone loss due to immobilization. IM animals treated with RIS lost nearly 50% of cancellous bone mass, while trabecular width and number were reduced by 31% and 25%, respectively. In both RIS-treated control and IM animals, overall bone formation parameters (mineralized bone surface fraction and bone formation rate) remained roughly at intact control levels; however, mineral apposition rate relative to intact control was reduced 40% in RIS-treated control and 86% in RIS-treated IM animals. These results indicate that high-dose RIS treatment might suppress osteoblastic function, especially under long-term disuse. Interestingly, bone resorption parameters in RIS-treated IM animals reached levels even higher than in vehicle-treated IM animals; values for eroded surface, osteoclast number, and surface were 84%, 53%, and 83% above vehicle-treated IM values, respectively. Our data indicate that risedronate treatment is partially effective in preventing cancellous bone loss during long-term disuse. Moreover, our results suggest that bisphosphonates can impair the ability of mature osteoclasts to resorb bone, but cannot overcome the strong stimulus for osteoclast recruitment caused by long-term disuse.

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Authors
Yang Li, C., Majeska, R. J., Laudier, D. M., Mann, R., & Schaffler, M. B.
Affiliations
  • Mount Sinai Hospital (US)
  • James J. Peters VA Medical Center (US)
Corresponding author
Schaffler, Mitchell B.
ORCID
Venue
Bone
Publisher
Elsevier BV
Published
2005-09
Volume
37
Issue
3
Pages
287-295
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2005.04.041
OpenAlex
W2058201651
Cited by
56
References
52
Citations by year
2021: 2 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 6 · 2012: 2
FWCI
4.18
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Bone (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Aeronautics and Space Administration
  • National Space Biomedical Research Institute
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41210, R01AR041210)
Topics
  • 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
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
risedronate, bisphosphonates, disuse bone loss, immobilization, trabecular bone, trabecular bone microarchitecture, osteoclast resorption, osteoblast activity, bone formation, mineral apposition rate, osteoclast recruitment, beagle dogs, metacarpal bones, osteoporosis prevention, histomorphometry, calcein
MeSH terms
Risedronic Acid, Animals, Bone and Bones, Dogs, Female, Immobilization, Etidronic Acid, Bone Density

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