Howard B.A. Baum, MD; Beverly M.K. Biller, MD; Joel S. Finkelstein, MD;
Kristin Baker Cannistraro, BS, RN; Daniel S. Oppenheim, MD, PhD; David A. Schoenfeld, PhD; Theresa
Hoskins Michel, PT, MS; Harriet Wittink, PT, MS; and Anne Klibanski, MD
‘ Background: Patients with adultonset growth hormone deﬁciency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body compo- siﬁon have not been convincingly shown.
Objective: To determine whether long-term growth hor- mone therapy at a dose adjusted to maintain normal insulin= like growth factor 1 (lGF~‘l) levels has clinical effects in patients with adult-onset growth hormone deﬁciency. Design: Randomized, placebo—c0ntrolled study. Setting: Tertiary referral center. Patients: 32 men with adult-onset growth hormone de- ficiency. Intervention: Growth hormone (initial daily dose, 10 /utg/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if lGF1 levels were elevated. Measurements: Body composition and bone mineral density of the lumbar spine, femoral neck, and proximal radius were measured by dual energy x-ray abs0rpliom— etry at 6-month inten/als. Markers of bone turnoverwere also measured during the ﬁrst 12 months of the study.
Results: Growth hormone therapy increased bone min- eral density in the lumbar spine by a mean (1 SD) of 5.1% 1 4.1% and bone mineral density in the femoral neck by 2.4% 1 3.5%. In the growth hormone group, signif- icant increases were seen in the following markers of bone turnover: osteocalcin (4.4 1 3.6 mg/L to 7.2 1 4.6 mg/L) and urinary pyridinoline (39.0 1 19.8 nmol/mmol
of creat- inine to 55.7 1 25.5 nmol/mmol of creatinine) and deoxy- pyridinoline (8.4 1 7.1 nmol/mmol of creatinine to 14.9 1 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31 .9% 1 6.5% to 28.3% 1 7.0%), and lean body mass in— creased (from 59.0 1 8.5 kg to 61.5 1 6.9 kg). These changes were signiﬁcantoompared with corresponding changes in the placebo group (P < 0.01 for all comparisons). Conclusions: Growth hormone administered to men with adult-onsetgrowth hormone deﬁciency at a dose adjusted according to semm IGF-1 levels increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects.