Estrogen deficiency is a potential cause for osteopenia in adult male patients with Noonan's syndrome

Osteopenia is frequently observed in patients with Turner's syndrome. By contrast, there is no report concerning bone metabolism in patients with Noonan's syndrome which comprises Turner's phenotypic characteristics without any sex chromosome abnormalities. In the present investigation, we determined bone mineral density (BMD) as well as serum and urine indices of bone turnover in two male patients with Noonan's syndrome. Both patients showed remarkably decreased BMD, measured at two sites on the lumbar spine (L2-L4) and the distal end of the radius using dual energy X-ray absorptiometry (DXA). Urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations were significantly elevated in both patients, and serum osteocalcin and carboxyterminal propeptide of type I procollagen (PICP) concentrations were elevated in one patient. Surprisingly, both patients had a low level of serum 17 beta-estradiol compared with control males, whereas they had normal levels of serum testosterone and dihydrotestosterone. Conjugated estrogens (Premarin 0.625 mg/day) were continued to be administered to these patients, followed up for 12 months. Urinary PYD and DPD concentrations gradually decreased, followed by an increase in their BMD. This is the first report that male patients with Noonan's syndrome showed osteopenia associated with increased bone resorption. Our data indicate that hypoestrogenism plays a potentially significant role in the abnormal bone metabolism in these patients.