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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 probiotics^19,20 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

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References

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