title: Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Yawkey 6E, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: mbredella@partners.org.
authors: Miriam A
authors: MA
authors: Bredella
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Bulfinch 457B, 55 Fruit Street, Boston, MA, USA.
authors: Anu V
authors: AV
authors: Gerweck
authors: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Yawkey 6E, 55 Fruit Street, Boston, MA 02114, USA.
authors: Lauren A
authors: LA
authors: Barber
authors: Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
authors: Anne
authors: A
authors: Breggia
authors: Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
authors: Clifford J
authors: CJ
authors: Rosen
authors: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Yawkey 6E, 55 Fruit Street, Boston, MA 02114, USA.
authors: Martin
authors: M
authors: Torriani
authors: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Bulfinch 457B, 55 Fruit Street, Boston, MA, USA.
authors: Karen K
authors: KK
authors: Miller
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000503:physiopathology; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D010919:Placebos; D017697:Premenopause / Q000187:drug effects; D011347:Procollagen / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D010446:Peptide Fragments; D010919:Placebos; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D013006:Growth Hormone
keywords: Bone; Bone marrow fat; Bone turnover; Growth hormone; MR spectroscopy; Obesity