Mechanisms of Glucocorticoid Action in Bone
Abstract
A bstract : Glucocorticoids cause profound effects on bone cell replication, differentiation, and function. Glucocorticoids increase bone resorption by stimulating osteoclastogenesis by increasing the expression of RANK ligand and decreasing the expression of its decoy receptor, osteoprotegerin. In accordance with the increase in bone resorption, glucocorticoids stimulate the expression of collagenase 3 by posttranscriptional mechanisms. The most significant effect of glucocorticoids in bone is an inhibition of bone formation. This is because of a decrease in the number of osteoblasts and their function. The decrease in cell number is secondary to a decrease in osteoblastic cell replication and differentiation, and an increase in the apoptosis of mature osteoblasts. Glucocorticoids decrease osteoblastic function directly and indirectly through the modulation of growth factor expression, receptor binding, or binding protein levels. Clinically, patients with glucocorticoid‐induced osteoporosis (GIOP) develop bone loss in the first few months of glucocorticoid exposure, and modest doses of glucocorticoids increase the risk of fractures of the spine and hip. Bisphosphonates inhibit bone resorption and prevent and revert the bone loss that follows glucocorticoid exposure. Anabolic agents, such as parathyroid hormone, stimulate bone formation and can increase bone mass in GIOP.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glucocorticoids inhibit synthesis of type I collagen, decreasing bone matrix available for mineralization.
“GCs also exert effects on their function by inhibiting the synthesis of type I collagen, the major component of bone extracellular matrix, with a consequent decrease in bone matrix available for mineralization.”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [4]
Glucocorticoids inhibit bone formation directly and indirectly by regulating the synthesis of factors present in the bone microenvironment.
“The most significant influences of glucocorticoids (GCs) are their inhibitory effects on bone formation, acting directly and indirectly by regulating the synthesis of factors present in the bone microenvironment [4].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [4]
Glucocorticoids reduce replication and prevent terminal differentiation of bone-forming cells and promote apoptosis of osteoblasts and osteocytes by activating caspase 3.
“GCs reduce replication and prevent the terminal differentiation of bone forming cells and additionally promote apoptosis of osteoblasts and osteocytes by activating caspase 3.”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [4]
Glucocorticoids indirectly decrease production of insulin-like growth factors and shift transforming growth factor-beta binding.
“Indirect actions of GCs involve decreased production of insulin-like growth factors (IGFs) and shifting transforming growth factor-β (TGF-β) binding [4, 5].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [4]
In functional GnRH deficiency, the pattern of GnRH secretion is altered, involving reduced frequency of pulsations and decreased pulse amplitude.
“In cases of functional GnRH deficiency the pattern of GnRH secretion is altered, involving reduced frequency of pulsations and decreased pulse amplitude [4, 5].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [4]
Cites
Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.10.7034 · Cited by 794 · see citing works
Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α
Cenci, S., Weitzmann, M. N., Roggia, C., Namba, N., Novack, D., Woodring, J., & Pacifici, R. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11066 · Cited by 705 · see citing works
Carbonare, L. D., Arlot, M. E., Chavassieux, P. M., Roux, J. P., Portero, N. R., & Meunier, P. J. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.1.97 · Cited by 309 · see citing works
BELLOWS, C. G., AUBIN, J. E., & HEERSCHE, J. N. M. (1987) · Endocrinology · doi:10.1210/endo-121-6-1985 · Cited by 306 · see citing works
Rubin, J., Biskobing, D. M., Jadhav, L., Fan, D., Nanes, M. S., Perkins, S., & Fan, X. (1998) · Endocrinology · doi:10.1210/endo.139.3.5778 · Cited by 113 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antiinflammatory Action of Glucocorticoids — New Mechanisms for Old Drugs
Rhen, T., & Cidlowski, J. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050541 · Cited by 3,149 · see citing works
Regulation of bone mass by Wnt signaling
Krishnan, V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28551 · Cited by 1,407 · see citing works
De Bosscher, K., Vanden Berghe, W., & Haegeman, G. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0006 · Cited by 898 · see citing works
Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
Czock, D., Keller, F., Rasche, F. M., & H??ussler, U. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544010-00003 · Cited by 886 · see citing works
Transforming Growth Factor-β1 to the Bone
Janssens, K., ten Dijke, P., Janssens, S., & Van Hul, W. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0001 · Cited by 710 · see citing works
Molecular mechanisms of glucocorticoid-induced osteoporosis.
Patschan, D., Loddenkemper, K., & Buttgereit, F. (2001) · Bone · doi:10.1016/s8756-3282(01)00610-x · Cited by 201 · see citing works
Involvement of the gut microbiota and barrier function in glucocorticoid-induced osteoporosis
Schepper, J. D., Collins, F., Rios-Arce, N. D., Kang, H. J., Schaefer, L., Gardinier, J. D., Raghuvanshi, R., Quinn, R. A., Britton, R., Parameswaran, N., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3947 · Cited by 199 · see citing works
Glucocorticoid induced autophagy in osteocytes
Xia, X., Kar, R., Gluhak-Heinrich, J., Yao, W., Lane, N. E., Bonewald, L. F., Biswas, S. K., Lo, W.-K., & Jiang, J. X. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.160 · Cited by 193 · see citing works
Kleiman, A., & Tuckermann, J. P. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.009 · Cited by 165 · see citing works
Co-morbidity in rheumatoid arthritis
Mikuls, T. R. (2003) · Best Practice & Research Clinical Rheumatology · doi:10.1016/s1521-6942(03)00041-x · Cited by 122 · see citing works
Neural regulation of bone and bone marrow
Maryanovich, M., Takeishi, S., & Frenette, P. S. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031344 · Cited by 114 · see citing works
Apoptotic Osteocytes and the Control of Targeted Bone Resorption
Plotkin, L. I. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0194-3 · Cited by 93 · see citing works
Ma, Y., Nyman, J. S., Tao, H., Moss, H. H., Yang, X., & Elefteriou, F. (2011) · Endocrinology · doi:10.1210/en.2010-0881 · Cited by 92 · see citing works
Skeletal involvement in adult patients with endogenous hypercortisolism
Chiodini, I., Torlontano, M., Carnevale, V., Trischitta, V., & Scillitani, A. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345601 · Cited by 78 · see citing works
Osteoporosis after transplantation
Kulak, C. A. M., Borba, V. Z. C., Júnior, J. K., & Custódio, M. R. (2012) · Current Osteoporosis Reports · doi:10.1007/s11914-011-0083-y · Cited by 67 · see citing works
RAMPs and CRLR expressions in osteoblastic cells after dexamethasone treatment
Uzan, B., de Vernejoul, M.-C., & Cressent, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.037 · Cited by 43 · see citing works
Pituitary Disorders and Osteoporosis
Bolanowski, M., Halupczok, J., & Jawiarczyk-Przybyłowska, A. (2015) · International Journal of Endocrinology · doi:10.1155/2015/206853 · Cited by 27 · see citing works
- Authors
- CANALIS, E., & DELANY, A. M.
- Affiliations
- University of Connecticut (US)
- Corresponding author
- CANALIS, ERNESTO
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2002-06
- Volume
- 966
- Issue
- 1
- Pages
- 73-81
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2153314004
- Cited by
- 406
- References
- 5
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 20 · 2019: 18 · 2018: 25 · 2017: 14 · 2016: 16 · 2015: 26 · 2014: 22 · 2013: 11 · 2012: 13
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK045227, DK 45227)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- glucocorticoids, glucocorticoid-induced osteoporosis, bone resorption, osteoclastogenesis, RANK ligand, osteoprotegerin, collagenase-3, osteoblasts, osteoblast apoptosis, bone formation, bisphosphonates, parathyroid hormone, bone loss, fracture risk
- MeSH terms
- Animals, Bone and Bones, Bone Resorption, Glucocorticoids, Growth Substances, Humans, Osteoblasts, Osteoclasts, Osteogenesis, Osteoporosis, Rodentia, Collagenases, Matrix Metalloproteinases, Matrix Metalloproteinase 13
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
