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

Maria G Vogiatzi 1Shanlee M Davis 2Judith L Ross 3 4

J Endocr Soc. 2021 Feb 10;5(4):bvab016. doi: 10.1210/jendso/bvab016. eCollection 2021 Apr 1.


Context: 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.

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

Methods: 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).

Results: 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).

Conclusion: 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.