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Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome
N Tahani1,2, L Nieddu3, G Prossomariti4
1Centre for Rare Diseases, Policlinico Umberto I, Rome, Italy. natascia.tahani@uniroma1.it.
Purpose:
To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT).
Methods:
Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT.
Results:
Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship.
Conclusions:
In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.
Insights
Klinefelter Syndrome (KS) patients have reduced bone density and impaired bone quality. Testosterone replacement therapy (TRT) did not improve these bone issues, despite some BMD increases.
Area of Science:
- Endocrinology
- Bone Metabolism
- Andrology
Background:
- Klinefelter Syndrome (KS) is a genetic condition associated with hypogonadism.
- Men with KS often exhibit altered body composition, including increased adiposity.
- Bone health is a significant concern in KS, but its specific characteristics require further elucidation.
Purpose of the Study:
- To evaluate bone damage in adult men with KS before and during testosterone replacement therapy (TRT).
- To compare bone mineral density (BMD), bone microarchitecture, and body composition between KS patients and controls.
Main Methods:
- Fifteen untreated hypogonadal men with KS and 26 age/BMI-matched controls were studied.
- Bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA), and fat measures were assessed using DEXA.
- KS patients underwent yearly assessments during three years of TRT.
Main Results:
- KS patients had higher fat mass and significantly reduced lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD compared to controls.
- Hip structure analysis revealed lower cortical thickness and higher buckling ratio in KS patients.
- TRT increased LS BMD but did not improve TBS or HSA parameters; fat measures were inversely associated with TBS.
Conclusions:
- Untreated hypogonadal men with KS exhibit reduced BMD and impaired femoral bone quality.
- Adiposity may negatively impact lumbar bone microarchitecture in KS.
- TRT was insufficient to reverse the detrimental effects on bone quality and microarchitecture in KS patients.
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