Use of oral corticosteroids and risk of fractures
Abstract
Treatment with oral corticosteroids is known to decrease bone density but there are few data on the attendant risk of fracture and on the reversibility of this risk after cessation of therapy. A retrospective cohort study was conducted in a general medical practice setting in the United Kingdom (using data from the General Practice Research Database [GPRD]). For each oral corticosteroid user aged 18 years or older, a control patient was selected randomly, who was matched by age, sex, and medical practice. The study comprised 244,235 oral corticosteroid users and 244,235 controls. The average age was 57.1 years in the oral corticosteroid cohort and 56.9 years in the control cohort. In both cohorts 58.6% were female. The most frequent indication for treatment was respiratory disease (40%). The relative rate of nonvertebral fracture during oral corticosteroid treatment was 1.33 (95% confidence interval [CI], 1.29–1.38), that of hip fracture 1.61 (1.47–1.76), that of forearm fracture 1.09 (1.01–1.17), and that of vertebral fracture 2.60 (2.31–2.92). A dose dependence of fracture risk was observed. With a standardized daily dose of less than 2.5 mg prednisolone, hip fracture risk was 0.99 (0.82–1.20) relative to control, rising to 1.77 (1.55–2.02) at daily doses of 2.5–7.5 mg, and 2.27 (1.94–2.66) at doses of 7.5 mg or greater. For vertebral fracture, the relative rates were 1.55 (1.20–2.01), 2.59 (2.16–3.10), and 5.18 (4.25–6.31), respectively. All fracture risks declined toward baseline rapidly after cessation of oral corticosteroid treatment. These results quantify the increased fracture risk during oral corticosteroid therapy, with greater effects on the hip and spine than forearm. They also suggest a rapid offset of this increased fracture risk on cessation of therapy, which has implications for the use of preventative agents against bone loss in patients at highest risk.
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?
Sex matching is essential since human male/female differences have been found in total brain volume, gray matter brain volume in specific regions and brain connectivity; sexual dimorphism of the brain has also been found during childhood.
“Moreover, sex matching is essential since human male/female differences have been found in total brain volume (697), gray matter brain volume in specific regions (698) and brain connectivity (699); sexual dimorphism of the brain has also been found during childhood (700)(reviewed in (689)).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [698]
Cites
Modeling and variable selection in epidemiologic analysis
Greenland, S. (1989) · American Journal of Public Health · doi:10.2105/ajph.79.3.340 · Cited by 2,208 · see citing works
Weinstein, R. S., Jilka, R. L., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2799 · Cited by 1,753 · cited 1× · see citing works
“(30) An alternative interpretation would be that a marked alteration in bone turnover, through induction of microarchitectural changes in bone quality, was responsible for the rapid change in fracture risk.”
BackgroundJick, H., Jick, S. S., & Derby, L. E. (1991) · BMJ · doi:10.1136/bmj.302.6779.766 · Cited by 839 · see citing works
The VAMP research multi-purpose database in the U.K.
Lis, Y. (1995) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(94)00137-f · Cited by 116 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Data Resource Profile: Clinical Practice Research Datalink (CPRD)
Herrett, E., Gallagher, A. M., Bhaskaran, K., Forbes, H., Mathur, R., van Staa, T., & Smeeth, L. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv098 · Cited by 2,667 · see citing works
Lamb, C. A., Kennedy, N. A., Raine, T., Hendy, P. A., Smith, P. J., Limdi, J. K., Hayee, B., Lomer, M. C. E., Parkes, G. C., Selinger, C., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318484 · Cited by 2,346 · see citing works
Feng, X., & McDonald, J. M. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130203 · Cited by 1,272 · 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
Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis.
Staa, T. P. V., Geusens, P., Bijlsma, J. W. J., Leufkens, H. G. M., & Cooper, C. (2006) · Arthritis & Rheumatism · doi:10.1002/art.22117 · Cited by 587 · see citing works
Self-citationVan Staa, T. P., Laan, R. F., Barton, I. P., Cohen, S., Reid, D. M., & Cooper, C. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11283 · Cited by 559 · see citing works
Self-citationCongenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556 · see citing works
Reid, D. M., Devogelaer, J.-P., Saag, K., Roux, C., Lau, C.-S., Reginster, J.-Y., Papanastasiou, P., Ferreira, A., Hartl, F., Fashola, T., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60250-6 · Cited by 527 · see citing works
Saag, K. G., Zanchetta, J. R., Devogelaer, J., Adler, R. A., Eastell, R., See, K., Krege, J. H., Krohn, K., & Warner, M. R. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24879 · Cited by 493 · see citing works
Glucocorticoid-Induced Osteoporosis
Buckley, L., & Humphrey, M. B. (2018) · New England Journal of Medicine · doi:10.1056/nejmcp1800214 · Cited by 438 · see citing works
Manolagas, S. C., & Parfitt, A. M. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.01.010 · Cited by 404 · see citing works
Bodai, B. I., & Tuso, P. (2015) · The Permanente Journal · doi:10.7812/tpp/14-241 · Cited by 397 · see citing works
Determinants of Muscle and Bone Aging
Curtis, E., Litwic, A., Cooper, C., & Dennison, E. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25001 · Cited by 375 · see citing works
Self-citationGlucocorticoid-induced osteoporosis
Briot, K., & Roux, C. (2015) · RMD Open · doi:10.1136/rmdopen-2014-000014 · Cited by 300 · see citing works
Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans
Womack, J. A., Goulet, J. L., Gibert, C., Brandt, C., Chang, C. C., Gulanski, B., Fraenkel, L., Mattocks, K., Rimland, D., Rodriguez-Barradas, M. C., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017217 · Cited by 261 · see citing works
Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy
Hardy, R. S., Zhou, H., Seibel, M. J., & Cooper, M. S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00097 · Cited by 258 · see citing works
The endothelium–bone axis in development, homeostasis and bone and joint disease
Tuckermann, J., & Adams, R. H. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00682-3 · Cited by 258 · see citing works
Exogenous cushing’s syndrome and glucocorticoid withdrawal
Hopkins, R. L., & Leinung, M. C. (2005) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2005.01.013 · Cited by 224 · see citing works
Clinical Applications of Vertebral Fracture Assessment by Dual-Energy X-Ray Absorptiometry
Lewiecki, E. M., & Laster, A. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1178 · Cited by 201 · see citing works
Cooper, M. S., Rabbitt, E. H., Goddard, P. E., Bartlett, W. A., Hewison, M., & Stewart, P. M. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.6.979 · Cited by 200 · see citing works
11β-hydroxysteroid dehydrogenase 1: translational and therapeutic aspects
Gathercole, L. L., Lavery, G. G., Morgan, S. A., Cooper, M. S., Sinclair, A. J., Tomlinson, J. W., & Stewart, P. M. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1050 · Cited by 196 · see citing works
Calcitonin Plays a Critical Role in Regulating Skeletal Mineral Metabolism during Lactation
Woodrow, J. P., Sharpe, C. J., Fudge, N. J., Hoff, A. O., Gagel, R. F., & Kovacs, C. S. (2006) · Endocrinology · doi:10.1210/en.2005-1616 · Cited by 195 · 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
Glüer, C.-C., Marin, F., Ringe, J. D., Hawkins, F., Möricke, R., Papaioannu, N., Farahmand, P., Minisola, S., Martínez, G., Nolla, J. M., et al. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1870 · Cited by 171 · see citing works
Glucocorticoids and bone: Local effects and systemic implications
Henneicke, H., Gasparini, S. J., Brennan-Speranza, T. C., Zhou, H., & Seibel, M. J. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.12.006 · Cited by 168 · 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
Mechanisms of glucocorticoid-induced osteoporosis.
Canalis, E. (2003) · Current Opinion in Rheumatology · doi:10.1097/00002281-200307000-00013 · Cited by 164 · see citing works
Pathogenic mechanisms of glucocorticoid-induced osteoporosis
Chen, M., Fu, W., Xu, H., & Liu, C.-J. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.03.002 · Cited by 146 · see citing works
STOCH, S. A., SAAG, K. G., GREENWALD, M., SEBBA, A. I., COHEN, S., VERBRUGGEN, N., GIEZEK, H., WEST, J., & SCHNITZER, T. J. (2009) · The Journal of Rheumatology · doi:10.3899/jrheum.081207 · Cited by 100 · see citing works
Understanding and managing corticosteroid-induced osteoporosis
Kobza, A. O., Herman, D., Papaioannou, A., Lau, A. N., & Adachi, J. D. (2021) · Open Access Rheumatology Research and Reviews · doi:10.2147/oarrr.s282606 · Cited by 84 · see citing works
Mazziotti, G., Porcelli, T., Bianchi, A., Cimino, V, Patelli, I., Mejia, C., Fusco, A., Giampietro, A., De Marinis, L., & Giustina, A. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0125 · Cited by 68 · see citing works
Bone metabolism and mass in women with Cushing’s syndrome and adrenal incidentaloma
Francucci, C. M., Pantanetti, P., Garrapa, G. G., Massi, F., Arnaldi, G., & Mantero, F. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01602.x · Cited by 65 · see citing works
Uncertainties in the prevention and treatment of glucocorticoid-induced osteoporosis
Hansen, K. E., Wilson, H. A., Zapalowski, C., Fink, H. A., Minisola, S., & Adler, R. A. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.362 · Cited by 65 · see citing works
Rangaswamaiah, S., Gangathimmaiah, V., Nordenstrom, A., & Falhammar, H. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00493 · Cited by 59 · see citing works
Osteoporosis and Fractures After Solid Organ Transplantation
Yu, T.-M., Lin, C.-L., Chang, S.-N., Sung, F.-C., Huang, S.-T., & Kao, C.-H. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.02.017 · Cited by 58 · see citing works
Glucocorticoid-induced osteoporosis
Silverman, S. L., & Lane, N. E. (2009) · Current Osteoporosis Reports · doi:10.1007/s11914-009-0005-4 · Cited by 50 · see citing works
The pituitary–adrenal axis and body composition
Fernandez-Rodriguez, E., Stewart, P. M., & Cooper, M. S. (2009) · Pituitary · doi:10.1007/s11102-008-0098-2 · Cited by 49 · see citing works
Cooper, M. S., Syddall, H. E., Fall, C. H. D., Wood, P. J., Stewart, P. M., Cooper, C., & Dennison, E. M. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02281.x · Cited by 48 · see citing works
Lan, G.-B., Xie, X.-B., Peng, L.-K., Liu, L., Song, L., & Dai, H.-L. (2015) · BioMed Research International · doi:10.1155/2015/413169 · Cited by 46 · see citing works
Möhlmann, J. E., Ezzafzafi, S., Lindemans, C. A., Jansen, M. H. A., Nierkens, S., Huitema, A. D. R., & van Luin, M. (2024) · Clinical Pharmacokinetics · doi:10.1007/s40262-024-01419-7 · Cited by 33 · see citing works
Schreiber, P. W., Bischoff-Ferrari, H. A., Boggian, K., Bonani, M., van Delden, C., Enriquez, N., Fehr, T., Garzoni, C., Hirsch, H. H., Hirzel, C., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191167 · Cited by 22 · see citing works
Kaji, H., Kuroki, Y., Murakawa, Y., Funakawa, I., Funasaka, Y., Kanda, F., & Sugimoto, T. (2010) · Osteoporosis International · doi:10.1007/s00198-009-1110-z · Cited by 16 · see citing works
Bone safety of low-dose glucocorticoids in rheumatic diseases
Saag, K. G. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12446 · Cited by 15 · see citing works
Goemaere, S., Liberman, U. A., Adachi, J. D., Hawkins, F., Lane, N., Saag, K. G., Schnitzer, T., Kaufman, J. M., Malice, M. P., Carofano, W., et al. (2003) · JCR Journal of Clinical Rheumatology · doi:10.1097/01.rhu.0000073586.28977.31 · Cited by 7 · see citing works
Yao, T.-C., Huang, Y.-W., Chang, S.-M., Tsai, S.-Y., Wu, A. C., & Tsai, H.-J. (2020) · Annals of Internal Medicine · doi:10.7326/m20-0432
- Authors
- Van Staa, T. P., Leufkens, H. G. M., Abenhaim, L., Zhang, B., & Cooper, C.
- Affiliations
- Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, Utrecht, the Netherlands
- Utrecht University (NL)
- Jewish General Hospital (CA)
- Procter & Gamble (United Kingdom) (GB)
- Southampton General Hospital (GB)
- Corresponding author
- Cooper, C.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-06-01
- Volume
- 15
- Issue
- 6
- Pages
- 993-1000
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W4255533032
- Cited by
- 1,263
- References
- 4
- Citations by year
- 2026: 35 · 2025: 40 · 2024: 42 · 2023: 38 · 2022: 58 · 2021: 52 · 2020: 67 · 2019: 44 · 2018: 51 · 2017: 41 · 2016: 33 · 2015: 45 · 2014: 37 · 2013: 51 · 2012: 45
- FWCI
- 36.47
- Type
- journal article
- Language
- en
- Open access
- closed
- 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)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Procter and Gamble
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- oral corticosteroids, fracture risk, hip fracture, vertebral fractures, forearm fractures, non-vertebral fractures, prednisolone dose, bone loss, osteoporosis prevention, respiratory diseases, dose dependence, Clinical Practice Research Datalink, general practice patients, secondary prevention
- MeSH terms
- Administration, Oral, Adrenal Cortex Hormones, Dose-Response Relationship, Drug, Female, Follow-Up Studies, United Kingdom, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Cohort Studies, Incidence, Medical Records Systems, Computerized, Fractures, Bone
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
