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. 2021 Mar 1;157(3):275-282.
doi: 10.1001/jamadermatol.2020.4968.

Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures

Alexander Egeberg  1   2 , Peter Schwarz  3 , Torben Harsløf  4 , Yuki M F Andersen  1 , Anton Pottegård  5 , Jesper Hallas  5 , Jacob P Thyssen  2   6
Affiliations

Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures

Alexander Egeberg et al. JAMA Dermatol. .

Abstract

Importance: Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored.

Objective: To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF.

Design, setting, and participants: This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019.

Exposures: Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group.

Main outcomes and measures: The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models.

Results: A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g.

Conclusions and relevance: These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Egeberg reported receiving grants, personal fees, and nonfinancial support from Pfizer, Inc, Eli Lilly and Company, Novartis International AG, and UCB; grants from Janssen Pharmaceutica; grants and personal fees from AbbVie and Bristol Myers Squibb; personal fees from Dermavant Sciences, Almirall SA, Leo Pharma A/S, Samsung Bioepis Co, Ltd, Galderma SA, Janssen Pharmaceutica, Sun Pharmaceutical Industries Ltd, and Galapagos NV; and research funding from the Danish National Psoriasis Foundation outside the submitted work. Dr Schwarz reported being an investigator for Ascendis Pharma and Kyowa Kirin Co, Ltd, outside the submitted work. Dr Harsløf reported receiving lecture fees from Amgen, Inc, Eli Lilly and Company, and AstraZeneca outside the submitted work. Dr Pottegård reported participating in research projects funded by Alcon, Almirall SA, Astellas Pharma Inc, AstraZeneca, Boehringer Ingelheim, Novo Nordisk A/S, Servier Laboratories, and Leo Pharma A/S, with funds paid to the institution where he was employed (no personal fees) outside the submitted work. Dr Hallas reported receiving grants from Astellas Pharma Inc, Nycomed, and Leo Pharma A/S outside the submitted work. Dr Thyssen reported serving as an adviser for Eli Lilly and Company, AbbVie, Pfizer, Inc, Sanofi Genzyme, and UNION Therapeutics; receiving speaker honoraria from Regeneron Pharmaceuticals, Inc, Leo Pharma A/S, and Sanofi-Genzyme; serving as an investigator for AbbVie, Pfizer, Inc, Eli Lilly and Company, Leo Pharma A/S, and Sanofi-Genzyme; and receiving an unrestricted grant from the Lundbeck Foundation outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Association Between Use of Potent and Very Potent Topical Corticosteroids (TCSs) and the Risk of Osteoporotic Outcomes
The fully adjusted models are adjusted for age, sex, socioeconomic status, cancer, diabetes, and use of proton pump inhibitors, statins, thiazide diuretics, histamine-receptor antagonists, psycholeptics, hormone therapy, contraceptives, cyclosporine A, systemic corticosteroids, and inhaled corticosteroids. HR indicates hazard ratio.
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