A meta-analysis of prior corticosteroid use and fracture risk

Kanis, John A.<sup>1</sup>; Johansson, Helena<sup>2</sup>; Oden, Anders<sup>2</sup>; Johnell, Olof<sup>3</sup>; de Laet, Chris<sup>4</sup>; Melton, III, L. Joseph<sup>5</sup>; Tenenhouse, Alan<sup>6</sup>; Reeve, Jonathan<sup>7</sup>; Silman, Alan J.<sup>8</sup>; Pols, Huibert A. P.<sup>9</sup>; Eisman, John A.<sup>10</sup>; McCloskey, Eugene V.<sup>1</sup>; Mellstrom, Dan<sup>11</sup>

Affiliations

¹Centre for Metabolic Bone Diseases (WHO Collaborating Centre), University of Sheffield Medical School, Sheffield, United Kingdom

²Consulting Statistician, Gothenburg, Sweden

³Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden

⁴Institute for Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands

⁵Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA

⁶Division of Bone Metabolism, The Montreal General Hospital, Montreal, Canada

⁷Strangeway’s Research Laboratory, Wort’s Causeway, Cambridge, United Kingdom

⁸ARC Epidemiology Unit, University of Manchester, Manchester, United Kingdom

⁹Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands

¹⁰Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia

¹¹Department of Geriatric Medicine, Goteborg University, Gothenburg, Sweden.

Abstract and keywords

The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of ∼42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.

Introduction: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk.

Materials and Methods: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted β coefficients.

Results: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD.

Conclusion: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.

Keywords: corticosteroids; fracture risk; meta-analysis; fracture threshold

Links

DOI: 10.1359/JBMR.040134

PubMed: ID15125788

WoS: 000221573400003

History

Received: 2003-07-22

Revised: 2003-11-17

Accepted: 2004-01-27

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2017	Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N; The National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. December 2017;12(1):1-24.
2009	Kanis JA, Oden A, Johansson H, Borgström F, Ström O, McCloskey E. FRAX^® and its applications to clinical practice. Bone. May 2009;44(5):734-743.
2020	Schini M, Vilaca T, Poku E, Harnan S, Sutton A, Allen IE, Cummings SR, Eastell R. The risk of hip and non-vertebral fractures in patients with Parkinson's disease and parkinsonism: a systematic review and meta-analysis. Bone. March 2020;132:115173.
2020	Yoshii I, Akita K. Cortical thickness relative to the transverse diameter of third metacarpal bone reflects bone mineral density in patients with rheumatoid arthritis. Bone. August 2020;137:115405.
2021	Hadaegh F, Asgari S, Toreyhi H, Eskandari F, Fahimfar N, Bozorgmanesh M, Hosseinpanah F, Azizi F. Sex-specific incidence rates and risk factors for fracture: a 16-year follow-up from the Tehran lipid and glucose study. Bone. May 2021;146:115869.
2022	Iki M, Fujimori K, Nakatoh S, Tamaki J, Ishii S, Okimoto N, Kamiya K, Ogawa S. Delayed initiation of anti-osteoporosis medications increases subsequent hip and vertebral fractures in patients on long-term glucocorticoid therapy: a nationwide health insurance claims database study in Japan. Bone. July 2022;160:116396.
2023	Iki M, Fujimori K, Nakatoh S, Tamaki J, Ishii S, Okimoto N, Kamiya K, Ogawa S. Real-world effectiveness of anti-osteoporosis medications for the prevention of incident hip and clinical vertebral fractures in patients on long-term glucocorticoid therapy: a nationwide health insurance claims database study in Japan. Bone. January 2023;166:116605.
2010	Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD; Scientific Advisory Council of Osteoporosis Canada. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Can Med Assoc J. November 23, 2010;182(17):1864-1873.
2010	Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA; Manitoba Bone Density Program. Independent clinical validation of a Canadian FRAX tool: fracture prediction and model calibration. J Bone Miner Res. November 2010;25(11):2350-2358.
2014	Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, McCloskey EV, Kanis JA, Bilezikian JP. Trabecular bone score: a noninvasive analytical method based upon the dxa image. J Bone Miner Res. March 2014;29(3):518-530.
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2005	Kanis JA, Johnell O. Requirements for DXA for the management of osteoporosis in Europe. Osteoporos Int. March 2005;16(3):229-238.
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2008	Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int. April 2008;19(4):385-397.
2008	Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A. Case finding for the management of osteoporosis with FRAX^®: assessment and intervention thresholds for the UK. Osteoporos Int. October 2008;19(10):1395-1408.
2008	Nguyen ND, Frost SA, Center JR, Eisman JA, Nguyen TV. Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks. Osteoporos Int. October 2008;19(10):1431-1444.
2011	Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Dawson-Hughes B, El-Hajj Fuleihan G, Johansson H, Leslie WD, Lewiecki EM, Luckey M, Oden A, Papapoulos SE, Poiana C, Rizzoli R, Wahl DA, McCloskey EV. Interpretation and use of FRAX in clinical practice. Osteoporos Int. September 2011;22(9):2395-2411.
2013	Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO); Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. January 2013;24(1):23-57.
2019	Kanis JA, Cooper C, Rizzoli R, Reginster J-Y; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO); Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. January 2019;30(1):3-44.
2016	Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S. Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop. March 18, 2016;7(3):171-181.
2012	Moayyeri A. Risk Assessment for Osteoporotic Fractures Among Men and Women from a Prospective Population Study: The EPIC-Norfolk Study [PhD thesis]. Cambridge, UK: University of Cambridge; 2012.
2016	Oei L. Epidemiological, Radiological and Genetic Aspects of Endocrine Bone Diseases [PhD thesis]. Erasmus University Rotterdam; December 14, 2016.
2020	Axelsson KF. Aspects of Fracture Prevention: The Role of Fracture Liaison Services and Alendronate [PhD thesis]. University of Gothenburg; 2020.
2009	Varga P. Prediction of Distal Radius Fracture Load Using HR-PQCT-Based Finite Element Analysis [PhD thesis]. Vienna University of Technology; December 2009.