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

Baum, Howard B. A.; Biller, Beverly M. K.; Finkelstein, Joel S.; Cannistraro, Kristin Baker; Oppenheim, Daniel S.; Schoenfeld, David; Michel, Theresa Hoskins; Wittink, Harriët; Klibanski, Anne

doi:10.7326/0003-4819-125-11-199612010-00003

Cited by 265 publications

(171 citation statements)

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“…After the initial 18-month period, a significant slope equivalent to an increase in BMD was reported for spine and hip measurements, but not for forearm and total body. When GH was compared with placebo, BMD only increased significantly at 2 of the 7 sites studied (18). During a further 18 months of observation after cross-over of GH and placebo treatment, BMD continuously increased in the group withdrawn from GH treatment, as did BMD in the patients newly started on GH at the spine and hip sites, but not BMD of forearm and total body.…”

Section: Discussionmentioning

confidence: 93%

“…An increase of BMD and BMC following GH treatment has been reported in several (9 -16) but not all (17) open trials. However, except for one study (18,19), the verification of such findings in randomised, placebo-controlled, double blinded trials with appropriate treatment doses of GH has not been possible. GH treatment for 6 months seems to induce a relative loss of BMD/BMC.…”

Section: Introductionmentioning

confidence: 99%

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Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Sneppen

Hoeck

Kollerup³

et al. 2002

European Journal of Endocrinology

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Objective: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. Design: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. Methods: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. Results: IGF-I levels increased from 63.2 mg/l (^10.1) to 193.6 (^25.8) mg/l (mean (^S.E.)) (P , 0:001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P , 0:001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of 21.8 (^3.8) in the GH-treated group vs an increase of 1.0 (^2.9)) in the placebo-treated group ðP ¼ 0:002Þ: Conclusions: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group.This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Sneppen

Hoeck

Kollerup³

et al. 2002

European Journal of Endocrinology

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“…33 The relevance of GH in the physiology of bone remodelling is well recognized with the GH/IGF-I system promoting bone turnover, with a prevalence of formation over reabsorption and a positive net balance at each remodelling site. In fact, long-term administration of rhGH has been shown to signi®cantly improve bone mineralization in GH de®cient adults, 34 who display reduced BMD and increased risk for fracture. 35 In the present study, a tendency of the serum markers of bone turnover (AP bone isoenzyme, serum osteocalcin and urinary hydroxyproline) to increase was observed in obese patients treated with rhGH but not in energy-restricted placebo-treated patients.…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women

et al. 1998

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OBJECTIVE: Severe energy restriction in the treatment of obesity is limited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and energy metabolism in obese patients undergoing severe dietary restriction. DESIGN: Single-blind placebo-controlled study. Twenty obese women were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and BMI, received vehicle only. SUBJECTS: Twenty women with simple obesity (age: 25.4 AE 1.07 y, BMI: 35.9 AE 0.35 kg/m 2 ). MEASUREMENTS: Plasma IGF-I and leptin, serum markers of bone turnover (serum bone isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expenditure (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks. RESULTS: Mean IGF-I plasma levels, not in¯uenced by energy restriction in patients receiving placebo, displayed a signi®cant increase in the group treated with rhGH. The mean weight reduction and fat mass loss were not signi®cantly different in the two groups (6.0 AE 0.51 vs 7.2 AE 0.30 kg, NS, and 5.36 AE 0.460 vs 4.28 AE 0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma leptin levels decreased signi®cantly in weight-reduced subjects receiving either rhGH (from 16.2 AE 2.37 to 6.4 AE 0.39 ng/ml, P`0.05) or placebo (from 14.3 AE 2.55 to 7.7 AE 3.77 ng/ml, P`0.05). On the contrary, the mean decrease of lean body mass (LBM) was signi®cantly lower in the GH-treated patients than in those receiving vehicle (1.52 AE 0.60 vs 3.79 AE 0.45 kg, P`0.05). In keeping with these ®ndings, the mean daily nitrogen balance was signi®cantly less negative in the GH-treated subjects than in the vehicle-injected patients (mean of the 4 week daily urine collections 7185.7 AE 40.33 vs 7363.9 AE 55.47 mmol/d, P`0.05, respectively). Further, a signi®cant reduction of mean REE was recorded in the energy-restricted placebo-treated patients (from 8807 AE 498 to 7580 AE 321 kJ/24 h, P`0.05), but not in the patients receiving rhGH (from 8367 AE 580 to 8903 AE 478 kJ/ 24 h, NS). Actually, when corrected for LBM, REE was even increased by GH administration (from 197.9 AE 11.76 to 219.3 AE 9.87 kJ/kg LBM/24 h, P`0.05), whereas it was unchanged in the placebo group (from 201.7 AE 13.85 to 190.0 AE 9.87 kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and density. CONCLUSION: rhGH treatment, though unable to enhance diet-induced weight and fat mass reduction...

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“…When administered to GH-deficient adults, GH increases lean body mass and decreases body fat [1]. Treatment of the 3T3-L1 preadipocyte cell line with GH prevents these cells from differentiating to adipocytes, suggesting that blocking preadipocyte differentiation is one mechanism whereby GH can regulate body fat homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Regulation of growth hormone expression by Delta-like protein 1 (Dlk1)

Ansell

Zhou

Schjeide

et al. 2007

Molecular and Cellular Endocrinology

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Delta-like protein 1 (Dlk1) is a transmembrane protein characterized by epidermal growth factor (EGF)-like repeats. Dlk1, which is also known as preadipocyte factor 1 (pref-1) because of its ability to inhibit preadipocyte differentiation, regulates the differentiation of several other cell types through unknown mechanisms. To elucidate Dlk1 functions, identification of Dlk1-regulated target genes is critical. The observation that Dlk1 is expressed in many endocrine tissues suggests that Dlk1 may have endocrine-related functions. Because Dlk1 is expressed in GH producing cells, we hypothesize that one function of Dlk1 is to regulate GH expression. We found that GH mRNA, protein, and secretion were significantly decreased in GH3 pituitary cell clones that stably express Dlk1. In contrast, Dlk1 expression was unable to alter prolactin expression. Co-transfection of GH3 cells with a GH promoter-regulated reporter gene showed that Dlk1 repressed GH promoter activity. Deletion and mutation analysis of the GH promoter indicated that Pit-1 binding sites in the GH promoter are required for Dlk1-mediated repression. Furthermore, Dlk1 expression represses Pit-1-mediated transcription when both proteins are co-expressed in MCF-7 cells. Deletion analysis of Dlk1 revealed that the ability of Dlk1 to regulate GH promoter activity is independent of both its EGF-like repeats and its ability to modulate MAP kinase activity. The observation that Dlk1 regulates GH expression identifies the first endocrine function of Dlk1, establishes GH as a Dlk1-regulated target gene, and provides a model system to facilitate studies of Dlk1-mediated signaling.

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

Abstract: 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.

Cited by 265 publications

References 30 publications

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women

Regulation of growth hormone expression by Delta-like protein 1 (Dlk1)

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