ESPE Abstracts

Background: Klinefelter syndrome (KS) is a male genetic disorder defined by the karyo type 47,XXY. Adult males with KS are at increased risk for osteoporosis, based on androgen deficiency. Androgen replacement is standard in adolescent and adults with KS, but has not been used earlier in childhood. We performed a clinical trial to study the effects of childhood, low-dose androgen replacement on bone density in boys with KS.

Objective and hypotheses: To measure baseline (BL) bone density and fracture risk in boys with KS and to determine the effects of androgen treatment for 2 years on these measures.

Method: This double-blind, placebo-controlled clinical trial (2005–2011, NCT00348946) randomized 93 boys with KS, ages 4–12 years, to two groups: oxandrolone (Ox, 0.06 mg/kg daily, oral) (n=46) or placebo (Pl) (n=47). Study visits occurred every 6 months for 2 years and included determination of history of prior fractures and a bone age X-ray. Bone density SDS were derived from the pediatric bone health index (BHI). BHI utilizes automated radiogrammetry from hand X-rays to measure cortical thickness. Statistical analysis included repeated measures ANCOVA.

Results: 93 boys enrolled and 80 (86%) subjects completed the 2-year study. BL bone density SDS was on average mildly reduced (−0.4±1.1). 7/93 boys (ages 4–10) had a history of prior fractures at BL, which is twice the population rate of fractures. Their mean bone density SDS was significantly less than the group with no prior fractures (−1.6±1.3 vs −0.3±1.0, P<0.004). Over the 2-year study, BHI SDS increased more in the Ox than in the Pl group (change from BL: 0.4±0.7 (Ox) vs −0.2±0.5 (Pl), P<0.001), indicating increased treatment-associated cortical bone mass in the Ox group.

Conclusion: Boys with KS and a prior history of fractures had decreased bone density (BHI). This technique of assessing cortical bone thickness may be a clinically relevant screen for increased fracture risk in KS. In the 2-year clinical trial, cortical bone mass by BHI increased significantly more in the Ox vs Pl group. Therefore, in a cohort at risk for osteoporosis, age-appropriate androgen replacement should be considered to optimize bone density in boys with KS.