Impact of GH administration on skeletal endpoints in adults with overweight/obesity

Author:

Dichtel Laura E12,Haines Melanie S12ORCID,Gerweck Anu V1,Bollinger Bryan1,Kimball Allison12ORCID,Schoenfeld David23,Bredella Miriam A24,Miller Karen K12

Affiliation:

1. Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

2. Harvard Medical School, Boston, Massachusetts, USA

3. Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA

4. Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA

Abstract

Objective Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. Design An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation. Methods In this study, 77 adults (53% men), aged 18–65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ −1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed. Results Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline. Conclusions GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.

Publisher

Oxford University Press (OUP)

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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