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Effects of Physiologic Growth Hormone Therapy on Bone Density and Body Composition in Patients with Adult-Onset Growth Hormone Deficiency

A Randomized, Placebo-Controlled Trial

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

1 December 1996 | Volume 125 Issue 11 | Pages 883-890

Background: Patients with adult-onset 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 composition have not been convincingly shown.

Objective: To determine whether long-term growth hormone therapy at a dose adjusted to maintain normal insulin-like growth factor 1 (IGF-1) levels has clinical effects in patients with adult-onset growth hormone deficiency.

Design: Randomized, placebo-controlled study.

Setting: Tertiary referral center.

Patients: 32 men with adult-onset growth hormone deficiency.

Intervention: Growth hormone (initial daily dose, 10 µg/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if IGF-1 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 absorptiometry at 6-month intervals. Markers of bone turnover were also measured during the first 12 months of the study.

Results: Growth hormone therapy increased bone mineral density in the lumbar spine by a mean (±SD) of 5.1% ± 4.1% and bone mineral density in the femoral neck by 2.4% ± 3.5%. In the growth hormone group, significant increases were seen in the following markers of bone turnover: osteocalcin (4.4 ± 3.6 mg/L to 7.2 ± 4.6 mg/L) and urinary pyridinoline (39.0 ± 19.8 nmol/mmol of creatinine to 55.7 ± 25.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 ± 7.1 nmol/mmol 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 corresponding changes in the placebo group (P < 0.01 for all comparisons).

Conclusions: Growth hormone administered to men with adult-onset growth hormone deficiency at a dose adjusted according to serum 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.

Author and Article Information

From the Massachusetts General Hospital, Boston, Massachusetts; and the Maine Medical Center, Portland, Maine.
Acknowledgments: The authors thank Drs. Andrew Perlman and Neil Gesundheit for their support of the study, Dr. Bernard Kliman for assistance with patient recruitment, Douglas Hayden for contributions to the statistical analysis, Dr. Leng Jiang for doing echocardiography, Jennifer Lord for study coordination and data entry, Jaime Paz for assistance with exercise testing, and the staff of the General Clinical Research Center at the Massachusetts General Hospital for their dedicated patient care.
Grant Support: In part by National Institutes of Health grants RR01066 and DK08783; Genentech, Inc.; and a grant from the American Philosophical Society.
Requests for Reprints: Anne Klibanski, MD, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, BUL457B, Boston, MA 02114.
Current Author Addresses: Dr. Baum: 7777 Forest Lane, Suite C-218, Dallas, TX 75230.

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