Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women

Abstract

Purpose: Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity.

Materials and methods: In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1.

Results: GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, a 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP.

Conclusion: GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover.

Trial registration: ClinicalTrials.gov NCT00131378.

Keywords: Bone; Bone marrow fat; Bone turnover; Growth hormone; MR spectroscopy; Obesity.

Conflict of interest statement

The authors have no conflict of interest to declare.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Mean (±SEM) change in P1NP (A) and undercarboxylated (uc) osteocalcin (B), over 6 months of GH administration versus placebo. *, p

Figure 2

1H-MR spectroscopy of bone marrow in a 40 year-old obese woman (BMI 34.9 kg/m2) before (A) and after (B) 6 months of GH administration. There is increased bone marrow lipid content following GH administration (0.44 vs 0.63 lipid-water ratio). For purposes of visual comparison, the amplitude of unsuppressed water was scaled identically.

Figure 3

Regression analysis of 6-month change in P1NP on 6-month change in IGF-1 (A), abdominal total adipose tissue (TAT) (B), 25-OH Vitamin D (C), and hsCRP (D).