There are few studies that have determined the effects of long-term GH replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD adults using dual energy X-ray absorptiometry (DEXA). The results show that GH replacement induced a sustained increase in BMD at all the skeletal sites measured. INTRODUCTION: Little is known of the effect of more than 5 years of GH replacement therapy on bone metabolism in GHD adults. PATIENTS AND METHODS: In this prospective, open-label, single-center study, which included 87 consecutive adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood onset GHD, the effect of 10 years of GH replacement on BMD was determined. RESULTS: The mean initial dose of GH was 0.98 mg/day. The dose was gradually lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end. The GH replacement induced a sustained increase in total, lumbar (L2-L4) and femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment response in IGF-I SDS was more marked in men, whereas women had a more marked increase in the total body BMC and the total body z-score. There was a tendency for women on estrogen treatment to have a larger increase in bone mass and density compared with women without estrogen replacement. CONCLUSIONS: Ten years of GH replacement in hypopituitary adults induced a sustained, and in some variables even a progressive, increase in bone mass and bone density. The study results also suggest that adequate estrogen replacement is needed in order to have an optimal response in BMD in GHD women.