Gonadal dysgenesis and bone metabolism

Gonadal dysgenesis is defined as congenital hypogonadism related to abnorma lities of the sex chromosomes. Because sex steroids play a central role in the acquisition and maintenance of bone mass, studies have been done to inv estigate bone status in patients with gonadal dysgenesis, particularly Turn er's syndrome and Klinefelter's syndrome, which are the two most common typ es. The severe estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated with a significant bone mass decrease ascribable to incr eased bone turnover, as shown by histological studies and assays of bone tu rnover markers. Estrogen therapy is followed by a significant bone mass gai n and a return to normal of bone turnover markers, suggesting that it is th e estrogen deficiency rather than the chromosomal abnormality that causes t he bone mass deficiency, although abnormalities in the renal metabolism of vitamin D have been reported. Combined therapy with estrogens and growth ho rmone seems beneficial during the prepubertal period. In Klinefelter's synd rome (47XXY), serum testosterone levels are at the lower end of the normal range and dihydrotestosterone levels are low. Histological studies show dep ressed osteoblast function and a decrease in 5-alpha-reductase activity res ponsible for partial tissue resistance to androgens. Assays of bone turnove r markers show evidence of increased bone turnover. The bone deficiency is most marked at the femoral neck and seems correlated with serum testosteron e and estradiol levels. Androgen therapy has favorable effects on the bone only if it is started before puberty. Recent data suggest that estrogens ma y contribute to the development of demineralization in KS and that bisphosp honate therapy may be beneficial. (C) 2001 Editions scientifiques et medica les Elsevier SAS.