Cited by 355Bone health and osteoporosis researchBone Metabolism and DiseasesEstrogen and related hormone effects

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Glucocorticoid-Treated Mice Have Localized Changes in Trabecular Bone Material Properties and Osteocyte Lacunar Size That Are Not Observed in Placebo-Treated or Estrogen-Deficient Mice

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Lane, Nancy E, Yao, Wei, Balooch, Mehdi, Nalla, Ravi K, Balooch, Guive, Habelitz, Stefan, Kinney, John H, Bonewald, Lynda F·2006·Journal of Bone and Mineral Research

DOI 10.1359/jbmr.051103PMC PMC1797152

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Abstract

UNLABELLED: This study compares changes in bone microstructure in 6-month-old male GC-treated and female ovariectomized mice to their respective controls. In addition to a reduction in trabecular bone volume, GC treatment reduced bone mineral and elastic modulus of bone adjacent to osteocytes that was not observed in control mice nor estrogen-deficient mice. These microstructural changes in combination with the macrostructural changes could amplify the bone fragility in this metabolic bone disease. INTRODUCTION: Patients with glucocorticoid (GC)-induced secondary osteoporosis tend to fracture at higher bone mineral densities than patients with postmenopausal osteoporosis. This suggests that GCs may alter bone material properties in addition to BMD and bone macrostructure. MATERIALS AND METHODS: Changes in trabecular bone structure, elastic modulus, and mineral to matrix ratio of the fifth lumbar vertebrae was assessed in prednisolone-treated mice and placebo-treated controls for comparison with estrogen-deficient mice and sham-operated controls. Compression testing of the third lumbar vertebrae was performed to assess whole bone strength. RESULTS: Significant reductions in trabecular bone volume and whole bone strength occurred in both prednisolone-treated and estrogen-deficient mice compared with controls after 21 days (p < 0.05). The average elastic modulus over the entire surface of each trabecula was similar in all the experimental groups. However, localized changes within the trabeculae in areas surrounding the osteocyte lacunae were observed only in the prednisolone-treated mice. The size of the osteocyte lacunae was increased, reduced elastic modulus around the lacunae was observed, and a "halo" of hypomineralized bone surrounding the lacunae was observed. This was associated with reduced (nearly 40%) mineral to matrix ratio determined by Raman microspectroscopy. These localized changes in elastic modulus and bone mineral to matrix ratio were not observed in the other three experimental groups. CONCLUSIONS: Based on these results, it seems that GCs may have direct effects on osteocytes, resulting in a modification of their microenvironment. These changes, including an enlargement of their lacunar space and the generation of a surrounding sphere of hypomineralized bone, seem to produce highly localized changes in bone material properties that may influence fracture risk.

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Authors: Lane, N. E., Yao, W., Balooch, M., Nalla, R. K., Balooch, G., Habelitz, S., Kinney, J. H., & Bonewald, L. F.
Affiliations: University of California, Davis (US)
Lawrence Berkeley National Laboratory (US)
University of California, San Francisco (US)
University of Missouri–Kansas City (US)
Corresponding author: Lane, Nancy E
ORCID: Lane, Nancy E
Yao, Wei
Balooch, Mehdi
Habelitz, Stefan
Kinney, John H
Bonewald, Lynda F
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 2006-03-01
Volume: 21
Issue: 3
Pages: 466-476
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1359/jbmr.051103
PMC: PMC1797152
OpenAlex: W2074016952
Cited by: 355
References: 47
Citations by year: 2026: 5 · 2025: 11 · 2024: 11 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 16 · 2016: 15 · 2015: 26 · 2014: 13 · 2013: 17 · 2012: 21
FWCI: 23.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
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)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5r01dk046661-05)
University of California, San Francisco
National Cancer Institute (P50CA095817)
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK46661-10)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043052, K24AR048841, 1-K24-AR-48841-02, P01AR046798, P01AR46798)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046661)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: glucocorticoid-induced osteoporosis, prednisolone, trabecular bone microarchitecture, bone material properties, elastic modulus, ovariectomy, estrogen deficiency, bone fragility, fracture risk, bone strength, lumbar vertebrae
MeSH terms: Animals, Bone and Bones, Elasticity, Estrogens, Glucocorticoids, Male, Mice, Inbred Strains, Osteocytes, Placebos, Prednisolone, Tomography, X-Ray Computed, Biomarkers, Bone Density, Bone Remodeling, Compressive Strength, Mice

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Glucocorticoid-Treated Mice Have Localized Changes in Trabecular Bone Material Properties and Osteocyte Lacunar Size That Are Not Observed in Placebo-Treated or Estrogen-Deficient Mice

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