Cortical Bone Mass is Low in Boys with Klinefelter Syndrome and Improves with Oxandrolone

Klinefelter syndrome (KS) is the most common sex aneuploidy in men. Affected males have hypogonadism, and, as a result, face an increased risk for osteoporosis and fractures. Androgen therapy is standard in adolescents and adults with KS but has not been used earlier in childhood.

To determine the effects of androgen treatment on bone mass in children with KS.

Randomized, double-blind, placebo-controlled clinical trial of oxandrolone (OX; 0.06 mg/kg daily; n = 38) versus placebo (PL; n = 40) for 2 years in boys with KS (ages 4-12 years). Changes in bone mass were examined by digital x-ray radiogrammetry, which determines the Bone Health Index (BHI) and standard deviation score (SDS).

BHI SDS was similar between groups at baseline (-0.46 ± 1.1 vs -0.34 ± 1.0 OX vs PL, P > .05) and higher in the OX group at 2 years (-0.1 ± 1.3 vs -0.53 ± 0.9, OX vs PL, P < .01). At baseline, BHI SDS values of all subjects were not normally distributed with 25.7% of subjects plotted below -1 SDS (P < .001), suggesting a deficit in bone mass. In total, 13.5% of subjects had sustained a fracture and their BHI SDS was lower than those with no fractures (-1.6 ± 1.3 vs -0.3 ± 1.0, P = .004).

Bone mass using BHI SDS is reduced in some children with KS and improves with OX. Since these individuals are at risk for osteoporosis, age-appropriate androgen replacement and future studies on bone health in children with KS should be further explored.