Efficacy and Tolerance of Treatment With an Aromatase Inhibitor (Anastrozole) to Limit the Progression of Bone Maturation Related to Pathological Adrenarche in Children With Silver-Russell or Prader-Willi Syndrome
Silver-Russell syndrome (SRS), which occurs secondary to an imprinting disorder due to the
anomalous methylation of chromosome 11 or due to a uniparental disomy of chromosome 7, is a
rare syndrome (ORPHA813, OMIM 180860) characterized by growth retardation with an
intrauterine onset, a normal head circumference, small postnatal size and major feeding
difficulties. Starting at a very young age, the rapid aging of bone can occur even in the
absence of central puberty, in association with the production of androgens by the adrenal
glands (adrenarche). This advanced bone maturation can compromise final size, even when the
child receives growth hormone (GH) treatment for several years.
Prader-Willi syndrome (PWS) is also a rare disease (ORPHA739, OMIM 176270), occurring
secondary to an imprinting disorder due to an anomaly in chromosome 15 (paternal deletion or
maternal disomy). These children also present feeding difficulties during the first few
years of life, as well as small size. They are frequently treated with GH, and their bone
age can increase during the course of adrenarche, as in certain patients with SRS.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
The rate of success in each of the two groups, evaluated using an X-ray of the left hand and wrist. Success is defined as a difference in the rate of progression of bone maturation of at least 9 months after 18 months of treatment.
Principal objective: To evaluate the efficacy of Anastrozole compared to placebo in slowing bone maturation during pathological adrenarche in children with SRS or PWS. Principal criterion of evaluation: The rate of success in each of the two groups, evaluated using an X-ray of the left hand and wrist. Success is defined as a difference in the rate of progression of bone maturation of at least 9 months after 18 months of treatment.
Irène Netchine, MD, PhD
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)