Management of children (usually boys) with short stature, advanced bone age, and subnormal adult height prediction remains a dilemma for pediatric endocrinologists. With the knowledge that estrogen is the main hormone stimulating epiphyseal maturation and fusion, aromatase inhibitors might be considered the best treatment option. The paucity of randomized clinical trial (RCT) data showing benefit aside, is the use of aromatase inhibitors safe in this group of patients? Estrogen plays a fundamental role in bone mass accrual. This RCT from Finland by Hero et al. examines markers of bone turnover, bone mineral density (BMD), and bone morphology in peripubertal boys treated with letrozole or placebo for 2 years. Previously, the investigators showed that letrozole treatment in pubertal boys is characterized by a high-testosterone, low-estrogen, low IGF-1 mileau, but BMD was not adversely affected. In the current study, in the letrozole group markers of bone resorption were initially increased, then decreased, while markers of bone formation were mostly unchanged. In the placebo group, markers of bone resorption and formation both increased over 2 years (coincident with pubertal development). BMD measured 12 months after cessation of treatment was not different between the 2 groups. Vertebral morphology (by a radiological technique called “instant vertebral assessment”) showed a similar proportion of vertebral anomalies in both groups. Thus, in the short term it appeared that letrozole treatment resulted in increased bone resorption that was not coupled with an increase in bone formation, while more prolonged treatment appeared to inhibit both bone resorption and formation. These changes may result from either increased testosterone or decreased estrogen. Although there was no clear effect on bone strength, these findings may give the clinician pause when considering aromatase inhibitor treatment. One wonder if similar effects would be seen with arimidex, a less potent aromatase inhibitor (at least as judged by relative testosterone increases). Steve LaFranchi, MD