Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

Abstract

Aromatase inhibitors (AIs), blockers of estrogen biosynthesis, delay bone maturation and therefore are used increasingly to promote growth in children and adolescents with growth disorders. The effects of treatment on skeletal health are largely unknown. Since estrogen deficiency is associated with various detrimental skeletal effects, we evaluated in this cross-sectional posttreatment study vertebral body morphology, dimensions and endplates, and intervertebral disks by the use of magnetic resonance imaging (MRI) in two cohorts of males previously treated with the AI letrozole or placebo. Males with idiopathic short stature received treatment with letrozole or placebo for 2 years during prepuberty or early puberty; males with constitutional delay of puberty received letrozole or placebo in combination with low-dose testosterone for 1 year during early or midpuberty. In males with idiopathic short stature, mild vertebral body deformities were found in 5 of 11 (45%) letrozole-treated subjects, whereas in the placebo group no deformities were detected ( p ¼ .01). In the cohort of males with constitutional delay of puberty, a high prevalence of endplate and intervertebral disk abnormalities was observed in both the letrozole-and the placebo-treated groups. We conclude that AI therapy during prepuberty or early puberty may predispose to vertebral deformities, which probably reflect impaired vertebral body growth rather than impaired bone quality and compression fractures. If AIs are used in growth indications, follow-up of vertebral morphology is indicated. ß

Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

“…As in our study, growth velocities were similar even though IGF levels were lower during letrozole therapy. After 2 years, PAH increased as a consequence of the slowed bone age progression in the treatment group, but the difference did not persist at later follow-up, when neither the 2 cm difference in height nor 4.1 cm difference in PAH was significant (24).…”

“…They reported no difference in growth velocities over 2 years, but the diminished progression in bone age resulted in a 5.9 cm gain in PAH after 2 years of letrozole compared with no increase from placebo. However, the gain in PAH did not persist in the 22 boys seen in long-term follow-up (24). Salehpour et al (25) treated 91 boys with CDGP and predicted short stature with letrozole, oxandrolone, or placebo for 2 years and reported an increased PAH from baseline (6.1 cm) in the letrozole group only.…”

Cognitive effects of aromatase inhibitor therapy in peripubertal boys

“…Despite the neutral findings of the current study, letrozole remains an experimental treatment for growth disorders, particularly due to its possible adverse effects on bone. Letrozole appears to suppress bone turnover and stimulate cortical bone growth in pubertal males (41), and the treatment may predispose boys to vertebral deformities (42).…”

Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia

“…Trials using high-dose aromatase inhibition reported deleterious effects. Mild vertebral deformities were detected in 45% of the letrozole-treated boys (38). In elderly men treated with anastrozole 1 mg daily for a year, spinal BMD was significantly decreased (39).…”