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Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis

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Abstract

Purpose

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear.

Methods

We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible.

Results

We included eight studies. Seven randomized 272 post-menopausal women, 61–69 years, to GH or control, for 6–24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = −0.01 [−0.04, 0.02]), total hip (WMD = 0 [−0.05, 0.06]) or femoral neck (WMD = 0 [−0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention.

Conclusion

GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.

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Acknowledgements

The authors would like to thank Dr. Elie Akl for his contribution to the methodology of the meta-analysis, Ms Aida Farha for her contribution to the systematic search and all study authors who generously provided data from their individual studies and answered study-related queries. Drs Barake, Arabi, El-Hajj Fuleihan, Tritos and Klibanski participated in study design; Drs Barake, Nakhoul and El Ghandour participated in article screening; Drs Barake and Nakhoul participated in data extraction and analysis; Drs Barake and Tritos participated in manuscript writing; All co-authors had the opportunity to revise, view and approve of the latest version of the manuscript. Research reported in this publication was supported by the Fogarty International Center and Office of Dietary Supplements of the National Institutes of Health under Award Number D43 TW009118. This funding supported the Scholars in Health Research Program (SHARP), American University of Beirut, Beirut, Lebanon. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Scholars in HeAlth Research Program, American University of Beirut, Beirut, Lebanon

    Maya Barake, Asma Arabi, Nancy Nakhoul & Ghada El-Hajj Fuleihan

  2. Clemenceau Medical Center, Beirut, Lebanon

    Maya Barake

  3. Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Diseases, American University of Beirut, Beirut, Lebanon

    Asma Arabi & Ghada El-Hajj Fuleihan

  4. Department of Internal Medicine, American University of Beirut, Beirut, Lebanon

    Nancy Nakhoul

  5. Bareen International Hospital, Abu Dhabi, United Arab Emirates

    Sarah El Ghandour

  6. Massacchusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Anne Klibanski & Nicholas A. Tritos

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  1. Maya Barake
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Correspondence to Maya Barake.

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Conflict of interest

Nicholas A Tritos has received institution-directed research support from Ipsen, Novo Nordisk, Novartis and Pfizer for work unrelated to this manuscript. Anne Klibanski has received research funding from Ipsen and consultancy from Chiasma. The remaining authors declare that they have no competing interests.

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Barake, M., Arabi, A., Nakhoul, N. et al. Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis. Endocrine 59, 39–49 (2018). https://doi.org/10.1007/s12020-017-1440-0

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