Withdrawal of long-term physiological growth hormone (GH) administration: Differential effects on bone density and body composition in men with adult-onset GH deficiency

Adults with acquired GH deficiency (GHD) have been shown to have osteopenia associated with a 3-fold increase in fracture risk and exhibit increased b ody fat and decreased lean mass. Replacement of GH results in decreased fat mass, increased lean mass, and increased bone mineral density (BMD). The p ossible differential effect of withdrawal of GH replacement on body composi tion compartments and regional bone mass is not known. We performed a rando mized, single blind, placebo-controlled 36-month cross-over study of GH us, placebo (PL) in adults with GHD and now report the effect of withdrawal of GH on percent body fat, lean mass, and bone density, as measured by dual e nergy x-ray absorptiometry. Forty men (median age, 51 yr; range, 24-64 yr) with pituitary disease and peak serum GH levels under 5 mu g/L in response to two pharmacological stimuli were randomized to GH therapy (starting dose , 10 mu g/kg.day, final dose 4 mu g/kg.day) us. PL for 18 months. Replaceme nt was provided in a physiological range by adjusting GH doses according to serum insulin-like growth factor I levels. After discontinuation of GH, bo dy fat increased significantly (mean +/- SEM, 3.18 +/- 0.44% P = 0.0001) an d returned to baseline. Lean mass decreased significantly (mean loss, 2133 +/- 539 g; P = 0.0016), but remained slightly higher (1276 +/- 502 g above baseline; P; 0.02581 than at study initiation. In contrast to the effect on body composition, BMD did not reverse toward p retreatment baseline after discontinuation of GH. Bone density at the hip c ontinued to rise during PL administration, showing a significant increase 1 0.0014 +/- 0.00042, g/cm(2) month; P = 0.005) between months 18-36. Every b one site except two (radial BMD and total bone mineral content), including those without a significant increase in BMD during the 18 months of GH admi nistration, showed a net increase over the entire 36 months. Therefore, the re is a critical differential response of the duration of GH action on diff erent body composition compartments. Physiological GH administration has a persistent effect on bone mass 18 months after discontinuation of GH.