Monitor Bone Health With High-Dose Topical Corticosteroids

Potent topical corticosteroids were associated with increased risk for osteoporosis, a Danish study suggested.

In a nationwide retrospective cohort study of over 720,000 adults, each doubling in cumulative dosing of potent and very potent topical corticosteroids — commonly used for chronic skin conditions like atopic dermatitis and psoriasis — raised the relative risk for development of osteoporosis by 3% (95% CI 2%-4%), reported Alexander Egeberg, MD, PhD, of the University of Copenhagen, and colleagues.

Similarly, there was also a 3% increased relative risk for major osteoporotic fracture associated with each doubling of cumulative topical corticosteroids dose (HR 1.03, 95% CI 1.02-1.04), they wrote in JAMA Dermatology.

This relationship was dose dependent, with no significant association seen between corticosteroid exposure of 500-999 g and major osteoporotic fracture (HR 1.01, 95% CI 0.99-1.03).

Doses of 1,000 g or higher, however, were associated with significantly increased risk for major fracture, with the highest risk seen at doses beyond 10,000 g in a fully adjusted model:

• 1,000 to 1,999 g: HR 1.05 (95% CI 1.02-1.08)
• 2,000 to 9,999 g: HR 1.10 (95% CI 1.07-1.13)
• 10,000-plus g: HR 1.27 (95% CI 1.19-1.35)

Similar patterns were seen for the risk of developing osteoporosis, with the highest risk seen among those with at least 10,000 g of exposure:

• 500 to 999 g: HR 1.06 (95% CI 1.02-1.09)
• 1,000 to 1,999 g: HR 1.09 (95% CI 1.05-1.13)
• 2,000 to 9,999 g: HR 1.10 (95% CI 1.06-1.14)
• 10,000-plus g: HR 1.24 (95% CI 1.13-1.36)

Egeberg’s group determined that corticosteroid exposure accounted for about 4.3% (95% CI 2.7%-5.8%) of the population-attributable risk for osteoporosis and 2.7% (95% CI 1.7%-3.8%) of major osteoporotic fractures.

However, there was no significant link between vertebral fractures and topical corticosteroid exposure at any dose.

“Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary cause of osteoporosis, and as many as 30% of all patients treated with systemic glucocorticoids for more than 6 months will develop GIOP,” noted Rebecca Jackson, MD, of Ohio State University in Columbus, in an accompanying editorial.

Egeberg’s group suggested that healthcare providers consider tapping into other corticosteroid-sparing therapeutic options for patients who need potent anti-inflammatory treatment on large body surfaces for prolonged periods, and attempt to mitigate osteoporosis risk.

The analysis included 723,251 adults who had filled a prescription for mometasone furoate or other potent topical corticosteroids like betamethasone valerate or clobetasol propionate, equivalent to a dose of at least 500 g. They were then compared with patients who had filled prescriptions of mometasone ranging between 200 to 499 g.

Osteoporosis was defined as an inpatient or outpatient hospital diagnosis, while a major osteoporotic fracture included a fracture of the hip, distal antebrachium, vertebrae, or humerus.

Jackson pointed out that this study does not provide any evidence that topical corticosteroids at conventional doses — which are the most commonly prescribed — hold any fracture risk.

She also noted that despite this dose-dependent risk, high-dose potent topical corticosteroids are still largely preferable to high-dose systemic glucocorticoids, arguing that “the number of patient-years of TCS [topical corticosteroids] use needed for 1 fracture is almost 4-fold lower than that reported for high-dose oral glucocorticoids (40 mg prednisolone for ≥30 days).”

“Until further data can provide evidence-based guidance on the long-term risks of exposure to high doses of TCSs and the reversibility of risk with TCS discontinuation, [this] study implies that TCSs should be stopped as soon as clinically warranted — ideally, well before reaching the cumulative dose thresholds considered by this study to be deleterious to bone,” Jackson stated. She suggested that providers consider switching to a non-glucocorticoid-based treatment if cumulative doses are nearing the highest thresholds.