Bone Alkaline Phosphatase and Growth in Pediatric Atopic Dermatitis

Eingun James Song, MD, dermatologist, director of clinical research, and co-chief medical officer at Frontier Dermatology, recently discussed bone growth in children with atopic dermatitis in a Dermatology Times Expert Perspectives custom video series. He reviewed bone alkaline phosphatase findings from dupilumab trials, the factors behind impaired growth, and how growth concerns shape treatment urgency.

Bone Alkaline Phosphatase in Dupilumab Trials

Song explained bone alkaline phosphatase is produced by osteoblasts and reflects the level of bone formation and mineralization. In growing children, it tracks well with skeletal growth, so numerically higher values are generally favorable at this age. Dupilumab-treated (Dupixent; Sanofi and Regeneron) patients in the trials had numerically higher values than placebo patients, whose values were not low but sat toward the lower end of the reference range.

“Of course, we cannot hang our head on just a single test alone,” Song said.

He noted the biomarker trend gains weight when paired with growth data. Together, the findings show a consistent trend toward catching up on growth in patients below the 40th percentile.

Factors Behind Impaired Bone Growth

Song identified 4 contributors to impaired growth: inflammation, poor sleep, medications affecting bone health such as topical and oral steroids, and restrictive diets driven by parental concern about food allergy.

“The reality is, in a patient with atopic dermatitis, the inflammation doesn’t exist in isolation,” Song said.

“It’s hard to say any one of those four factors is more important than the other,” he added.

Adjusting for topical corticosteroid use still showed a benefit for dupilumab-treated patients, so steroids do not explain everything. The children in the studies were shorter but had weight and BMI on the higher side, suggesting malnutrition is not the sole explanation.

Song pointed to itch-driven sleep loss as potentially one of the most relevant drivers. Poor sleep may limit growth hormone secretion, which ties to insulin-like growth factor and bone growth. He described the effect of elevated IL-4 and IL-13 on osteoblast function as more theoretical, but listed chronic inflammation among the main drivers.

Prioritizing Treatment in Younger Children

Growth is less central in an older child without severe disease, Song said. For a younger child who looks smaller than expected, he prioritizes starting an effective and safe medication as soon as possible. Only one systemic agent is FDA-approved for moderate to severe atopic dermatitis below age 12, typically dupilumab.

Phototherapy is often slow and can be difficult for caretakers to schedule, Song said. Topicals are important but often fall short of clear skin and good sleep.

“If a patient is really falling off the growth curves, we really need to prioritize our most effective therapies,” Song said.

Song tells caretakers there is a limited window to intervene. For children losing ground on growth curves, dupilumab is often the therapy he prioritizes.