March 2021 Hot Topic: Bone Health Risks With High-Dose Topical Corticosteroids

Mother and daughter cooking


                                                                                                                                                                                                                    Read time 3 minutes

Corticosteroid therapy is often used to alleviate symptoms associated with inflammatory conditions such as arthritis, asthma, psoriasis, and atopic dermatitis. Systemic corticosteroids are known to have negative effects on bone health, with glucocorticoid-induced osteoporosis the most common secondary cause of osteoporosis,1,2 leading to fractures in 30 to 50% of patients.3,4 Few large-scale studies have explored associations between topical corticosteroid use and adverse bone-related events; however, researchers recently analyzed prescription data from over 700,000 adult patients and found increased risks.

Topical Corticosteroids & Osteoporosis/Fracture Risk

In January 2021, JAMA Dermatology published a large retrospective cohort study that reported an association between cumulative exposure to potent and very potent topical corticosteroids (TCSs) and risk of osteoporosis and major osteoporotic fracture.5 The pharmaceutical formulation and delivery vehicle (water-based liquid, cream, powder) may influence the potency of topical steroids.6 The potency of TCSs in this cohort study were determined in accordance with the World Health Organization’s ATC/DDD Index with potent (e.g., mometasone furoate or betamethasone 17 valerate) and very potent (e.g., clobetasol propionate) TCSs included in the analysis.5

Study Data & Analysis

The study used data from Danish nationwide registries to find patients who had been treated with potent or very potent TCSs between January 1, 2003, and December 3, 2017.5 The filled prescription data sets were converted in equipotent doses to mometasone furoate (1 mg/g), and those adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (n = 723,251 Danish adults).5 Patients who had filled prescriptions of 200 to 499 g were used as a reference group, while the other patients were grouped by level of cumulative exposure:5

  • 500 to 999 g (25.8%) (n = 186,359)
  • 1,000 to 1,999 g (15.4%) (n = 111,203)
  • 2,000 to 9,999 g (13.0%) (n = 94,334)
  • at least 10,000 g (1.9%) (n = 13,448)
Study Results & Conclusions

The results of the study suggest that while the risk for average TCS users remains low, there is a dose-response effect for cumulative use of potent and very potent TCSs leading to an increased risk of osteoporosis and major osteoporotic fracture.5 Specifically:

  • The *population-attributable risk (PAR) of any exposure (i.e., ?500 g) compared with non-exposed individuals (i.e., 200-499 g) was 4.3% for osteoporosis and 2.7% for major osteoporotic fracture.5
  • A 3% relative risk increase for both osteoporosis and major osteoporotic fracture was observed per doubling of the cumulative TCS dose.5

Researchers concluded that due to the findings, alternative treatment options could be considered for inflammatory skin conditions in addition to early osteoporosis evaluations for those patients using large amounts of, or undergoing a prolonged therapy with, potent and very potent TCSs.5 For some populations, the adverse bone health impact from high-dose TCS use may compound existing risk factors, create an additive effect, and result in a more significant osteoporosis and fracture risk. For example, patients with low bone mineral density scores or prior osteoporotic fracture; patients experiencing advanced age, menopause, or malnutrition; or patients prescribed other medications associated with bone loss have potentially compromised bone health already and may seek other treatment strategies to avoid additional adverse effects.

Clinical Considerations

TCSs of varying potency and dosage levels are often used to treat dermatological conditions such as psoriasis, which affects an estimated 7.4 million US adults,7 and atopic dermatitis, which is prevalent in approximately 10.7% of children and 7.2% of adults in the United States.8 Beyond steroid prescriptions, how do we address the underlying causes of chronic skin conditions?

Addressing intestinal permeability and microbiome imbalances that impact immune system function and overall health are potential paths to better outcomes. An anti-inflammatory diet that also addresses any noted nutrient deficiencies,9,10 supplements such as fish oil, vitamin D, and probiotics,10-13 exercise,14 and mindfulness therapies such as meditation15 have all shown efficacy in the treatment of chronic skin conditions. And for those patients with compromised bone homeostasis due to corticosteroid therapies, similar functional medicine approaches may address underlying chronic inflammation and optimize bone health. For example, research suggests that an anti-inflammatory diet,16 exercise,17 and supplements such as omega-3 fatty acids18 and probiotics19,20 may positively impact bone density and quality.

While periodic use and low doses of TCSs for inflammatory skin conditions may be effective for temporary symptom suppression, high doses and chronic use have elevated health risks. Personalized lifestyle interventions that focus on alleviating systemic inflammation are additional treatment options that may help to improve not only symptoms, but also address underlying health concerns and optimize overall wellness.

*Please note that for the Egeberg 2021 study, the PAR estimates the proportion of osteoporosis or fracture in the study population that is attributable to the TCS exposure. The researchers calculated the PAR estimate according to the formula P × (HR – 1)/[P × (HR – 1) + 1], where P is the prevalence of the exposure and HR is the hazard ratio.5

Related Articles

Environmental and Lifestyle Determinants of Allergic Diseases

Intestinal Permeability and Inflammatory Triggers

The Role of the Microbiome in Immune-Related Diseases


  1. Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018;61(1):7-16. doi:10.1007/s12020-018-1588-2
  2. Mirza F, Canalis E. Management of endocrine disease: secondary osteoporosis: pathophysiology and management. Eur J Endocrinol. 2015;173(3):R131-R151. doi:10.1530/EJE-15-0118
  3. Fraser LA, Adachi JD. Glucocorticoid-induced osteoporosis: treatment update and review. Ther Adv Musculoskelet Dis. 2009;1(2):71-85. doi:10.1177/1759720X09343729
  4. Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis [published correction appears in Arthritis Rheumatol. 2017;69(11):2246]. Arthritis Rheumatol. 2017 Aug;69(8):1521-1537. doi:10.1002/art.40137
  5. Egeberg A, Schwarz P, Harsløf T, et al. Association of potent and very potent topical corticosteroids and the risk of osteoporosis and major osteoporotic fractures. JAMA Dermatol. Published online January 20, 2021. doi:10.1001/jamadermatol.2020.4968
  6. Spada F, Barnes TM, Greive KA. Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids. Australas J Dermatol. 2018;59(3):e168-e174. doi:10.1111/ajd.12762
  7. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516. doi:10.1016/j.jaad.2013.11.013
  8. Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26-30. doi:10.1016/j.jid.2016.07.012
  9. Kim MJ, Kim SN, Lee YW, Choe YB, Ahn KJ. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. Nutrients. 2016;8(12):789. doi:10.3390/nu8120789
  10. Ford AR, Siegel M, Bagel J, et al. Dietary recommendations for adults with psoriasis or psoriatic arthritis from the medical board of the National Psoriasis Foundation: a systematic review. JAMA Dermatol. 2018;154(8):934-950. doi:10.1001/jamadermatol.2018.1412
  11. Nosrati A, Afifi L, Danesh MJ, et al. Dietary modifications in atopic dermatitis: patient-reported outcomes. J Dermatolog Treat. 2017;28(6):523-538. doi:10.1080/09546634.2016.1278071
  12. Vaughn AR, Foolad N, Maarouf M, Tran KA, Shi VY. Micronutrients in atopic dermatitis: a systematic review. J Altern Complement Med. 2019;25(6):567-577. doi:10.1089/acm.2018.0363
  13. Navarro-López V, Martínez-Andrés A, Ramírez-Boscá A, et al. Efficacy and safety of oral administration of a mixture of probiotic strains in patients with psoriasis: a randomized controlled clinical trial. Acta Derm Venereol. 2019;99(12):1078-1084. doi:10.2340/00015555-3305
  14. Ko SH, Chi CC, Yeh ML, Wang SH, Tsai YS, Hsu MY. Lifestyle changes for treating psoriasis. Cochrane Database Syst Rev. 2019;7(7):CD011972. doi:10.1002/14651858.CD011972.pub2
  15. Gamret AC, Price A, Fertig RM, Lev-Tov H, Nichols AJ. Complementary and alternative medicine therapies for psoriasis: a systematic review. JAMA Dermatol. 2018;154(11):1330-1337. doi:10.1001/jamadermatol.2018.2972
  16. Malmir H, Saneei P, Larijani B, Esmaillzadeh A. Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies. Eur J Nutr. 2018;57(6):2147-2160. doi:10.1007/s00394-017-1490-3
  17. Hettchen M, von Stengel S, Kohl M, et al. Changes in menopausal risk factors in early postmenopausal osteopenic women after 13 months of high-intensity exercise: the randomized controlled ACTLIFE-RCT. Clin Interv Aging. 2021;16:83-96. doi:10.2147/CIA.S283177
  18. Shen D, Zhang X, Li Z, Bai H, Chen L. Effects of omega-3 fatty acids on bone turnover markers in postmenopausal women: systematic review and meta-analysis. Climacteric. 2017;20(6):522-527. doi:10.1080/13697137.2017.1384952
  19. Lambert MNT, Thybo CB, Lykkeboe S, et al. Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Am J Clin Nutr. 2017;106(3):909-920. doi:10.3945/ajcn.117.153353
  20. Nilsson AG, Sundh D, Bäckhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018;284(3):307-317. doi:10.1111/joim.12805