Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement

To determine whether testosterone replacement therapy reverses the detrimental effects of hypogonadism on bone density, we measured the total body, lumbar spine and proximal femur bone mineral density (BMD) by dual-energy X-ray absorptiometry in 14 patients with Klinefelter's syndrome on long-term testosterone replacement therapy and compared the results with 14 age- and sex-matched normal controls. Seven of the patients were receiving oral testosterone undecanoate thrice daily (240 mg/day) and the others were having intramuscular testosterone enanthate injections once every 3 weeks (250 mg/injection). Their serum testosterone levels were maintained within the normal limits (10–40 nmol/l). We showed that patients on testosterone replacement had decreased amount of bone density in the left femoral neck when compared with the controls (p<0.01). Similar decreases were also observed in the left Ward's triangle (p<0.01) and in the left trochanter (p<0.05). There were no significant differences in the total body and the lumbar spine measurements in these two groups of subjects. No correlation was found between the BMD values of femur and the duration of testosterone treatment in the patients with Klinefelter's syndrome. The type of testosterone treatment was also not associated with significant differences in BMD. In conclusion, sufficient testosterone replacement with currently available methods does not reverse the decrease in bone mass associated with hypogonadism in patients with Klinefelter's syndrome.