Abstract：
OBJECTIVE: The role of osteocalcin (OCN) in pubertal development, male hypogonadism, and the effect of testosterone (Te) replacement therapy (TRT) remains unclear. We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism.
METHODS: This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement.
RESULTS: The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (p = 0.017) and FSH levels (p = 0.004) in adults, and significantly declined after 3 months of TRT (p = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (p = 0.004), calculated free Te (p = 0.016), the Te/LH (p = 0.010), and calculated free Te/LH ratios (p = 0.031).
CONCLUSIONS: In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults.
METHODS: This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement.
RESULTS: The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (p = 0.017) and FSH levels (p = 0.004) in adults, and significantly declined after 3 months of TRT (p = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (p = 0.004), calculated free Te (p = 0.016), the Te/LH (p = 0.010), and calculated free Te/LH ratios (p = 0.031).
CONCLUSIONS: In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults.
摘要：
目的：骨钙蛋白（OCN）在青春期发育中的作用，男性性腺功能减退,睾酮（Te）替代疗法（TRT）的效果尚不清楚。我们的目的是调查克氏综合征（KS）男性患者的总OCN（tOCN）浓度，成人高促性腺激素性腺功能减退症模型。
方法：这项回顾性纵向研究调查了2007年至2021年在学术转诊中心的254名男性KS患者（47,XXY），归类为（1）青春期前，(2)青春期,（3）成人。所有青春期前患者均未接受治疗。成年患者被分类为（1）性腺，（2）性腺功能减退，(3)接收TRT。我们还分析了在TRT开始之前和之后3个月具有可用tOCN水平的18名成年患者。
结果：tOCN水平在整个生命周期中根据青春期状态而变化，在性腺最高，在TRT受试者中显着较低，与成年人的LH（p=0.017）和FSH水平（p=0.004）相关，在成年KS队列中，TRT治疗3个月后显著下降(p=0.006)。HPG轴激素水平在青春期前男孩中没有相关性。对年龄和体重指数的调整证实了先前的结果，并揭示了与总Te的显着负相关（p=0.004），计算自由Te(p=0.016)，Te/LH（p=0.010），和计算的游离Te/LH比率（p=0.031）。
结论：在KS中，男性促性腺激素性性腺功能减退的模型，在正常的青春期前和青春期发育期间，tOCN水平与性腺功能无关，但与成人睾丸功能较差和HPG刺激程度较高有关。TRT急剧降低成人的tOCN水平。
方法：这项回顾性纵向研究调查了2007年至2021年在学术转诊中心的254名男性KS患者（47,XXY），归类为（1）青春期前，(2)青春期,（3）成人。所有青春期前患者均未接受治疗。成年患者被分类为（1）性腺，（2）性腺功能减退，(3)接收TRT。我们还分析了在TRT开始之前和之后3个月具有可用tOCN水平的18名成年患者。
结果：tOCN水平在整个生命周期中根据青春期状态而变化，在性腺最高，在TRT受试者中显着较低，与成年人的LH（p=0.017）和FSH水平（p=0.004）相关，在成年KS队列中，TRT治疗3个月后显著下降(p=0.006)。HPG轴激素水平在青春期前男孩中没有相关性。对年龄和体重指数的调整证实了先前的结果，并揭示了与总Te的显着负相关（p=0.004），计算自由Te(p=0.016)，Te/LH（p=0.010），和计算的游离Te/LH比率（p=0.031）。
结论：在KS中，男性促性腺激素性性腺功能减退的模型，在正常的青春期前和青春期发育期间，tOCN水平与性腺功能无关，但与成人睾丸功能较差和HPG刺激程度较高有关。TRT急剧降低成人的tOCN水平。
