[Growth hormone deficiency, its influence on bone mineral density and risk of osteoporotic fractures]

Growth hormone (GH) is the most abundant hormone from all pituitary hormones. Linear bone growth increases as a result of complex hormonal reactions, in particular as an effect of insulin-like growth factor I (IGF I). GH has a key role in longitudinal bone growth and in reaching peak bone mass (PBM) during childhood and adolescence. PBM is a important risk predictor of osteoporotic fractures. Despite closure of epiphyseal growth plates, effect of GH/IGF on bone turnover, bone mass, bone density and strength lasts by regulation of bone remodelation. Many authors have observed low BMD in hypopituitarismus, especially in growth hormone deficient (GHD) patients. Initially reduction of BMD has been described after 6-12 months of therapy with growth hormone. When therapy continued, BMD has normalized or was even higher in comparison with the beginning of the therapy. Reduction in BMD results from increased remodelation space after enhanced activation of bone turnover during GH therapy. Decrease in bone growth and PBM also influences incidence of fractures in elderly patients. It has been shown, that 18-24 months of GH therapy slightly increased BMD in a group of adult men with adult onset of GHD (AO-GHD), whereas in women it has not significantly changed. Three previous studies have proved increased fracture risk in patients with GHD. Not only high number of patients, but also an applicable control group, confirmation of potential risk factors such as BMI, smoking, sex, calcium intake and physical activity are needed to estimate the risk of fractures. Holmer et al. have analysed fracture incidence in GHD patients on replacement therapy compared to normal population. No increase of fracture risk in AO GHD women has been observed, but GHD was associated with higher fracture risk in women with childhood onset of GHD (CO GHD). Men have even lower incidence of fractures matched with control group. There are also sexual differences in effects of GH on bone. Women have in general higher levels of GH secretion, but the normal range for serum IGF-I is similar in men and women. In a placebo controlled double blind study, where men and women with GHD received the same dose of GH on m2/body, the increase of serum IGF-I levels was higher in men. Possible explanation for sexual differences in response to GH therapy is that sexual hormones affect GH secretion.