Prolonged, Potent Topical Corticosteroid Use Linked to Osteoporotic Events

Alexander Egeberg, MD, PhD

Findings from a new study indicated that potent or high cumulative amounts of topical corticosteroids was associated with increased risk of osteoporosis and major osteoporotic fractures.

Given the widespread use of topical corticosteroids in patients with psoriasis, atopic dermatitis, and other inflammatory diseases, assessing the risk of prolonged use of such medications may prove valuable from a public health perspective.

Therefore, a team led by Alexander Egeberg, MD, PhD, Herlev and Gentofte Hospital, University of Copenhagen, Denmark, conducted a nationwide retrospective cohort study to evaluate associations between topical corticosteroids and risks related to osteoporosis.

“Because some patients may consume very large quantities of topical corticosteroids per year, the effect of high cumulative use of potent or very potent topical corticosteroids on the risk for osteoporosis and major osteoporotic fractures needs to be quantified to better support treatment decisions in patients requiring long-term treatment,” Egeberg and colleagues wrote.

Osteoporotic Risks of Topical Corticosteroids

The investigators defined topical corticosteroid exposure as filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone.

Patients considered exposed were compared with patients using filled prescriptions of 200-499 g — the study reference group.

The primary endpoints for the study were hospital inpatient or outpatient diagnosis of osteoporosis or major osteoporotic fractures, which was determined in accordance with the World Health Organization’s definition of a fracture of the hip, distal antebrachium, vertebrae, or humerus.

As such, Egeberg and his team evaluated a total of 723,251 adults treated with at least 200 g of mometasone. A majority (52.8%) were women, and the mean age was 52.8 years.

Furthermore, 25.8% of participants were considered exposed to 500-999 g of mometasone. A smaller percentage (13.0%) were exposed to 1000-1999 g, followed by 1.9% who were exposed to at least 10,000 g of mometasone.

The investigators thus reported that hazard ratios of osteoporosis and major osteoporotic factures increased with increasing use of topical corticosteroids.

As such, in terms of risk of osteoporosis, the hazard ratio was 1.06 (95% CI, 1.02-1.09) for exposure to 500-999 g, 1.09 (95% CI, 1.05-1.13) for 1000-1999 g, 1.10 (95% CI, 1.06-1.14) for 2000-9999 g, and 1.24 (95% CI, 1.13-1.36) for exposure to ≥10, 000 g.

In terms of major osteoporotic fractures, the hazard ratio for 500-999 g was 1.01 (95% CI, 0.99-1.03), followed by 1.05 (95% CI, 1.02-1.08) for 1000-1999 g, 1.10 (95% CI, 1.07-1.13) for 2000-9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to ≥10,000 g.

The team also noted that a doubling of the cumulative topical corticosteroid dose was associated with a 3% relative risk increase of both osteoporosis and major osteoporotic fractures (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 major osteoporotic fractures.

And, finally, analysis showed that exposures to ≥10,000 g of mometasone was the lowest exposure for 1 additional patient to be harmed from major osteoporotic fractures.

Implications for Treatment

These findings underscore the importance of careful consideration when prescribing corticosteroids, systemic or topical, in patients with dermatological or inflammatory conditions.

“Although dosage consideration is crucial when prescribing all types of medication, topical corticosteroids are normally prescribed with little thought regarding the applied quantity per skin surface area,” the investigators wrote.

They noted that alternative topical and systemic therapies may offer themselves as better options for inflammatory skin conditions, considering such conditions may require large quantities or prolonged treatment. Nevertheless, they acknowledged, efficacy of such interventions do require further research.

“Alternatively, earlier evaluation of and prophylaxis for osteoporosis and prophylactic therapy may be considered in patients with extensive use of potent and very potent topical corticosteroids,” Egeberg and colleagues suggested.

The study, “Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures,” was published online in JAMA Dermatology.