Research Suggests Low Bone Mineral Density Linked to Epidermolysis Bullosa

A recent study found that delayed puberty in children and young adults with epidermolysis bullosa (EB) may impact low bone mineral density (BMD).

EB is a severe set of rare genetic skin conditions that lead to skin fragility, chronic inflammation, and malnutrition affecting pubertal development. The comorbidity of delayed pubertal development was assessed regarding its effect on skeletal health and BMD.

The study, led by Halley Wasserman MD, MS, CCD, and Andrea Dumenigo, BS, was conducted through electronic medical records at the Cincinnati Children's Hospital Medical Center.

“While further investigation is necessary to determine the impact of low BMD on fracture, pain and osteoporosis risk in patients with EB, this study highlights the need for pubertal screening and bone health monitoring during childhood and adolescence to address skeletal health concerns in this population,” Wasserman and colleagues wrote.

Background Information

The investigators used 186 total EB patients’ electronic medical records (EMR) from the Cincinnati Children's Hospital Medical Center. They confirmed EB patients' ages to be <30 years by the time of their initial encounters from January 2010 to September 2020.

The researchers used natural language processing software to categorize EB patients’ pubertal status in 3 possible ways: early, normal, or delayed. Patients’ pubertal status was categorized as delayed if the following elements were indicated by EMR:

• No testicular enlargement by age 14 years in males
• A prescription for testosterone in males
• No breast development by age 13 years for females
• No menses by age 16 for females
• Delayed puberty reported by a pediatric endocrinologist

Dual energy x-ray absorptiometry was used to assess BMD, reporting levels as being low if patients’ height-adjusted Z-scores are <2.0. The investigators used age, sex, and race-specific reference ranges for those whose data was examined. They used body mass index (BMI), B subtype, gastric tube (GT) status, and pubertal status as BMD co-variants for their research.

Research Findings

The investigators found that 29% of EB patients analyzed had low BMD and most of these cases occurred before the patients turned 10 years old. They reported that 23% of patients who reached adolescence did not show any indications of puberty during the normal age range of before 13 for females and before 14 for males. The results also indicated that BMD Z-scores also declined in these patients.

The researchers also found that physical activity interventions involving weight-bearing exercise were the most effective for growing bone mass during EB patients’ prepubertal and peripubertal phases. They found that patients with delayed puberty were more likely to be identified as  predominant wheelchair users compared to those reporting normal puberty, at 61% compared to 18%, respectively (P = 0.008).

“Patients with EB, especially (recessive dystrophic EB), are at risk for delayed puberty and this may contribute to the increased prevalence of low BMD in these individuals,” they wrote. “While further investigation is necessary to determine the impact of low BMD on fracture, pain and osteoporosis risk in patients with EB, this study highlights the need for pubertal screening and bone health monitoring during childhood and adolescence to address skeletal health concerns in this population.”

This study, “Prevalence of delayed puberty and low bone density in patients with epidermolysis bullosa: Insight from a large single center's experience,” was published on Wiley Online Library.