EFFECTS OF PHYSIOLOGICAL GROWTH-HORMONE THERAPY ON BONE-DENSITY AND BODY-COMPOSITION IN PATIENTS WITH ADULT-ONSET GROWTH-HORMONE DEFICIENCY- A RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Background: Patients with adult-onset growth hormone deficiency have r educed bone density and increased fat mass. Growth hormone at high dos es may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body composition have not been convincingly shown. Objective: To determine whether lon g-term growth hormone therapy at a dose adjusted to maintain normal in sulin-like growth factor 1 (IGF-1) levels has clinical effects in pati ents with adult-onset growth hormone deficiency. Design: Randomized, p lacebo-controlled study. Setting: Tertiary referral center. Patients: 32 men with adult-onset growth hormone deficiency. intervention: Growt h hormone (initial daily dose. 10 mu g/kg of body weight) or placebo f or 18 months. The growth hormone dose was reduced by 25% if IGF-1 leve ls were elevated. Measurements: Body composition and bone mineral dens ity of the lumbar spine, femoral neck, and proximal radius were measur ed by dual energy x-ray absorptiometry at 6-month intervals. Markers o f bone turnover were also measured during the first 12 months of the s tudy. Results: Growth hormone therapy increased bone mineral density i n the lumbar spine by a mean (+/- SD) of 5.1% +/- 4.1% and bone minera l density in the femoral neck by 2.4% +/- 3.5%. in the growth hormone group, significant increases were seen in the following markers of bon e turnover: osteocalcin (4.4 +/- 3.6 mg/L to 7.2 +/- 4.6 mg/L) and uri nary pyridinoline (39.0 +/- 19.8 nmol/mmol of creatinine to 55.7 +/- 2 5.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 +/- 7.1 nmol/m mol of creatinine to 14.9 +/- 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31.9% +/- 6.5 % to 28.3% +/- 7.0%), and lean body mass increased (from 59.0 +/- 8.5 kg to 61.5 +/- 6.9 kg). These changes were significant compared with c orresponding changes in the placebo group (P < 0.01 for all comparison s). Conclusions: Growth hormone administered to men with adult-onset g rowth hormone deficiency at a dose adjusted according to serum IGF-1 l evels increases bone density and stimulates bone turnover, decreases b ody fat and increases lean mass, and is associated with a low incidenc e of side effects.