Endocrine Abstracts

Introduction: Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent and it has been traditionally related to low testosterone levels. However, low BMD can be observed also in patients with normal testosterone levels and testosterone replacement therapy does not necessarily increase bone mass in these patients. Nothing is known about vitamin D levels and supplementation in KS. In this study we determine vitamin D status and bone mass in KS subjects and compare the efficacy of testosterone therapy and vitamin D supplementation on BMD.

Methods: A total of 127 non-mosaic KS patients and 60 age-matched male controls were evaluated with reproductive hormones, 25-hydroxyvitamin D, PTH, and bone densitometry by DEXA. Patients with hypogonadism and/or 25-hydroxyvitamin D deficiency were treated with testosterone-gel 2% and/or calcifediol and re-evaluated after 24 months of treatment.

Results: 25-hydroxyvitamin D levels were significantly lower in KS patients with respect to controls, and they had significantly lower lumbar and femoral BMD. The percentage of osteopenia/osteoporosis in subjects with 25-hydroxyvitamin D deficiency was higher with respect to subjects with normal 25-hydroxyvitamin D and was not related to the presence/absence of low testosterone levels. Subjects treated with calcifediol or testosterone+calcifediol had a significant increase in lumbar BMD after treatment. No difference was found in testosterone-treated group.

Conclusions: These data highlight that low 25-hydroxyvitamin D levels have a more critical role than low testosterone levels in inducing low BMD in KS subjects. Furthermore, vitamin D supplementation seems to be more effective than testosterone replacement therapy alone in increasing BMD.