MADRID – – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.
A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.
“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.
His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”
He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.
Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.
In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.
In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H2 receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.
Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.
In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.
A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.
“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.
A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.
“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.
Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.