Cited by 258Bone health and osteoporosis researchAdrenal Hormones and DisordersEstrogen and related hormone effects

Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy

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Hardy, Rowan S, Zhou, Hong, Seibel, Markus J, Cooper, Mark S·2018·Endocrine Reviews

Abstract

Osteoporosis associated with long-term glucocorticoid therapy remains a common and serious bone disease. Additionally, in recent years it has become clear that more subtle states of endogenous glucocorticoid excess may have a major impact on bone health. Adverse effects can be seen with mild systemic glucocorticoid excess, but there is also evidence of tissue-specific regulation of glucocorticoid action within bone as a mechanism of disease. This review article examines (1) the role of endogenous glucocorticoids in normal bone physiology, (2) the skeletal effects of endogenous glucocorticoid excess in the context of endocrine conditions such as Cushing disease/syndrome and autonomous cortisol secretion (subclinical Cushing syndrome), and (3) the actions of therapeutic (exogenous) glucocorticoids on bone. We review the extent to which the effect of glucocorticoids on bone is influenced by variations in tissue metabolizing enzymes and glucocorticoid receptor expression and sensitivity. We consider how the effects of therapeutic glucocorticoids on bone are complicated by the effects of the underlying inflammatory disease being treated. We also examine the impact that glucocorticoid replacement regimens have on bone in the context of primary and secondary adrenal insufficiency. We conclude that even subtle excess of endogenous or moderate doses of therapeutic glucocorticoids are detrimental to bone. However, in patients with inflammatory disorders there is a complex interplay between glucocorticoid treatment and underlying inflammation, with the underlying condition frequently representing the major component underpinning bone damage.

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  • Chronic glucocorticoid excess decreases bone mineral density and leads to osteoporosis.

    “the deleterious effects of chronic glucocorticoid excess on bone mineral density leading to osteoporosis are well established (258).”

    From Adrenal incidentaloma (2020) · cites this paper as [258]

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Research works printed but not linked: 4

  1. Keeney DS, Jenkins CM, Waterman MR. Devel- opmentally regulated expression of adrenal 17a- hydroxylase cytochrome P450 in the mouse embryo. Endocrinology. 1995;136(11):4872-4879.
  2. Gomez-Sanchez E, Gomez-Sanchez CE. The multi- faceted mineralocorticoid receptor. Compr Physiol. 2014;4(3):965-994.
  3. Vande Berg BC, Malghem J, Lecouvet FE, Devogelaer JP, Maldague B, Houssiau FA. Fat conversion of femoral marrow in glucocorticoid-treated patients: a cross-sectional and longitudinal study with magnetic resonance imaging. Arthritis Rheum. 1999; 42(7):1405-1411.
  4. Rabbitt EH, Lavery GG, Walker EA, Cooper MS, Stewart PM, Hewison M. Prereceptor regulation of glucocorticoid action by 11b-hydroxysteroid de- hydrogenase: a novel determinant of cell pro- liferation. FASEB J. 2002;16(1):36-44.

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Authors
Hardy, R. S., Zhou, H., Seibel, M. J., & Cooper, M. S.
Affiliations
  • University of Birmingham (GB)
  • Anzac Research Institute (AU)
  • The University of Sydney (AU)
Corresponding author
Cooper, Mark S
Venue
Endocrine Reviews
Published
2018-06-13
Volume
39
Issue
5
Pages
519-548
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
OpenAlex
W2808631980
Cited by
258
References
271
Citations by year
2026: 28 · 2025: 32 · 2024: 34 · 2023: 46 · 2022: 35 · 2021: 33 · 2020: 31 · 2019: 14 · 2018: 5
FWCI
4.25
Type
journal article
Language
en
Open access
Locations
  • Endocrine Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • Versus Arthritis (20843)
  • Medical Research Council (MR/P021220/1)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
glucocorticoids, bone health, glucocorticoid-induced osteoporosis, Cushing's disease, subclinical Cushing's syndrome, autonomous cortisol secretion, glucocorticoid replacement therapy, adrenal insufficiency, glucocorticoid receptor, bone metabolism, inflammatory diseases, glucocorticoid metabolism
MeSH terms
Cushing Syndrome, Glucocorticoids, Humans, Osteoporosis, Bone Density, Hormone Replacement Therapy, Pituitary ACTH Hypersecretion

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