Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment.

After prolonged treatment (76.4+/-10 and 70.1+/-12.3 months, respectively) (mean+/-SE) with testosterone enanthate (250 mg i.m. every 3 weeks), bone mineral density (BMD) and bone metabolism were evaluated in 12 patients (aged 29.3+/-1.4 yr) affected by idiopathic hypogonadotropic hypogonadism (IHH), in 8 patients (29.6+/-2.6 yr) affected by Klinefelter's syndrome (KS), and in 10 healthy men (30.6+/-1.7 yr) matched according to age and BMI. Spinal BMD in IHH was significantly lower than in controls (0.804+/-0.04 vs 1.080+/-0.01 g/cm2; p<0.001), while there was no difference in neck BMD (0.850+/-0.01 vs 0.948+/-0.02 g/cm2). Neither spinal (0.978+/-0.05 g/cm2) nor neck (0.892+/-0.03 g/cm2) BMD in KS were significantly different from controls. Six IHH and one KS subjects were osteoporotic, while 6 IHH and 2 KS subjects were osteopenic. A significant inverse correlation was found between spinal BMD and age at the treatment onset in IHH (r=-0.726, p=0.007). In IHH there were significant increases in bone formation (alkaline phosphatase=318.3+/-33.9 vs 205.4+/-20.0 IU/l; osteocalcin=13.44+/-1.44 vs 8.57+/-0.94 ng/ml; p<0.05) and in bone resorption (urinary cross-linked N-telopeptides of type I collagen=149.1+/-32.3 vs 47.07+/-8.4 nmol bone collagen equivalents/mmol creatinine; p<0.05) compared to controls, while such differences were not present in KS. Our results outline the importance of BMD evaluation in all hypogonadal males. Nevertheless, bone loss is a minor characteristic of KS, while it is a distinctive feature of IHH. Therefore, early diagnosis and age-related replacement therapy coupled with a specific treatment for osteoporosis could be useful in preventing future severe bone loss and associated skeletal morbidity.