Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-05T10:42:49.012Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis

Published online by Cambridge University Press:  10 January 2017

Hayden F. Atkinson ,
Rebecca F. Moyer ,
Daniel Yacoub ,
Dexter Coughlin  and
Trevor B. Birmingham
Hayden F. Atkinson*
Affiliation:
Wolf Orthopaedic Biomechanics Lab, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario School of Physical Therapy, Faculty of Health Sciences, University of Western Ontario
Rebecca F. Moyer
Affiliation:
Wolf Orthopaedic Biomechanics Lab, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario School of Physical Therapy, Faculty of Health Sciences, University of Western Ontario
Daniel Yacoub
Affiliation:
Faculty of Health Sciences, University of Western Ontario
Dexter Coughlin
Affiliation:
School of Occupational Therapy, Dalhousie University
Trevor B. Birmingham
Affiliation:
Wolf Orthopaedic Biomechanics Lab, Fowler Kennedy Sport Medicine Clinic, University of Western Ontario School of Physical Therapy, Faculty of Health Sciences, University of Western Ontario
*
†La correspondance et les demandes de tire-à-part doivent être adressées à : / Correspondence and requests for offprints should be sent to: Hayden Atkinson Faculty of Health Sciences, Wolf Orthopaedic Biomechanics Lab Fowler Kennedy Sport Medicine Clinic Room 1230, 3M Centre University of Western Ontario London, ON N6A 3K7 ([email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Résumé

Notre objectif était d’évaluer l’efficacité de l’hormone de croissance humaine recombinante (HCH) sur la densité minérale osseuse (DMO) chez les personnes âgées de 50 ans et plus, ayant une fonction pituitaire normale, qui risquent de développer l’ostéoporose. Nous avons passé en revue systématiquement les essais cliniques randomisés (ECR), examinant six bases de données, et ont réalisé des méta-analyses pour examiner les effets de la HCH sur la DMO dans la colonne lombaire et le col du fémur. Les données au sujet de l’incidence des fractures, les biomarqueurs du métabolisme osseux et les événements indésirables ont également été extraites et analysées. Treize ECR ont rempli les critères d’admissibilité. Effets de mise en commun de différentes tailles ne suggèrent aucun effet significatif de la HCH sur la DMO. Les valeurs de l’effet de mise en commun étaient plus grandes, mais insignifiantes, comparativement au placebo. La HCH a eu un effet significatif sur plusieurs marqueurs pour le métabolisme osseux. On a observé un taux significativement plus élevé d’évènements indésirables dans les groupes HCH. La méta-analyse des ECR suggère que le traitement par la HCH pour personnes ayant ou à risque de développer l’ostéoporose entraîne des augmentations très petites et insignifiantes de la DMO.

Keywords

agingosteoporosisbone mineral densitygrowth hormonesystematic reviewmeta-analysisvieillissementostéoporosedensité minérale osseusehormone de croissanceexamen systématiqueméta-analyse
Type
Articles
Information
Canadian Journal on Aging / La Revue canadienne du vieillissement , Volume 36 , Issue 1 , March 2017 , pp. 41 - 54
Check for updates
Copyright
Copyright © Canadian Association on Gerontology 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

* The authors acknowledge Travis Saunders for his assistance and feedback on the original draft of the manuscript and development of the systematic review.
Hayden Atkinson’s work was supported by the Western University Graduate Research Scholarship (Western University), the Collaborative Training Program in Musculoskeletal Health Research (Bone & Joint Institute, Western University), and the Science Undergraduate Research Award (University of Prince Edward Island). Rebecca Moyer’s work was supported by the Western University Faculty of Health Sciences Postdoctoral Fellowship program, and the Collaborative Training Program in Musculoskeletal Health Research (Bone & Joint Institute, Western University). Trevor Birmingham’s work was supported by the Canada Research Chair program, and the Bone & Joint Institute of Western University.

References

Anawalt, B. D., & Merriam, G. R. (2001). Neuroendocrine aging in men: Andropause and somatopause. Endocrinology and Metabolism Clinics of North America, 30(3), 647–669.Google Scholar
Barake, M., Klibanski, A., & Tritos, N. A. (2014). Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: A meta-analysis. The Journal of Clinical Endocrinology & Metabolism, 99(3), 852–860.Google Scholar
Beshyah, S. A., Thomas, E., Kyd, P., Sharp, P., Fairney, A., & Johnston, D. G. (1994). The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism. Clinical Endocrinology, 40(3), 383–391.CrossRefGoogle ScholarPubMed
Brixen, K., Kassem, M., Nielsen, H. K., Loft, A. G., Flyvbjerg, A., & Mosekilde, L. (1995). Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: A dose response study. Journal of Bone and Mineral Research, 10(12), 1865–1874.Google Scholar
Burger, H., De Laet, C., Van Daele, P., Weel, A., Witteman, J., Hofman, A., & Pols, H. (1998). Risk factors for increased bone loss in an elderly population: The Rotterdam Study. American Journal of Epidemiology, 147(9), 871–879.Google Scholar
Christmas, C., O’Connor, K. G., Harman, S. M., Tobin, J. D., Münzer, T., Bellantoni, M. F., … & Blackman, M. R. (2002). Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 57(1), M12–M18.Google Scholar
Clemmesen, B., Overgaard, K., Riis, B., & Christiansen, C. (1993). Human growth hormone and growth hormone releasing hormone: A double-masked, placebo-controlled study of their effects on bone metabolism in elderly women. Osteoporosis International, 3(6), 330–336.Google Scholar
Corpas, E., Harman, S. M., & Blackman, M. R. (1993). Human growth hormone and human aging. Endocrine Reviews, 14(1), 20–39.Google Scholar
Dalén, N., & Olsson, K. E. (1974). Bone mineral content and physical activity. Acta Orthopaedica Scandinavica, 45(1–4), 170–174.Google Scholar
Dougherty, G. (1996). Quantitative CT in the measurement of bone quantity and bone quality for assessing osteoporosis. Medical Engineering & Physics, 18(7), 557–568.CrossRefGoogle ScholarPubMed
Gonnelli, S., Cepollaro, C., Montomoli, M., Gennari, L., Montagnani, A., Palmieri, R., & Gennari, C. (1997). Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: A placebo controlled study. Clinical Endocrinology, 46(1), 55–61.Google Scholar
Guyatt, G. H., Oxman, A. D., Vist, G. E., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., & Schünemann, H. J. (2008). GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 336, 924–926.CrossRefGoogle ScholarPubMed
Hedström, M., Sääf, M., Brosjö, E., Hurtig, C., Sjöberg, K., Wesslau, A., & Dalén, N. (2004). Positive effects of short-term growth hormone treatment on lean body mass and BMC after a hip fracture: A double-blind placebo-controlled pilot study in 20 patients. Acta Orthopaedica Scandinavica, 75(4), 394–401.Google Scholar
Higgins, J. P., Altman, D. G., Gøtzsche, P. C., Jüni, P., Moher, D., Oxman, A. D., … & Sterne, J. A. (2011). The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ, 343:d5928.CrossRefGoogle ScholarPubMed
Higgins, J. P., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414), 557–560.Google Scholar
Holloway, L., Butterfield, G., Hintz, R. L., Gesundheit, N. & Marcus, R. (1994). Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. The Journal of Clinical Endocrinology & Metabolism, 79(2), 470–479.Google Scholar
Holloway, L., Kohlmeier, L., Kent, K., & Marcus, R. (1997). Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women. The Journal of Clinical Endocrinology & Metabolism, 82(4), 1111–1117.Google Scholar
Kanis, J. A., Johnell, O., De Laet, C., Johansson, H., Odén, A., Delmas, P., … & McCloskey, E. V. (2004). A meta-analysis of previous fracture and subsequent fracture risk. Bone, 35(2), 375–382.CrossRefGoogle ScholarPubMed
Kotzmann, H., Riedl, M., Pietschmann, P., Schmidt, A., Schuster, E., Kreuzer, S., … & Mayer, G. (2004). Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis. Journal of Nephrology, 17(1), 87–94.Google Scholar
Krantz, E., Trimpou, P., & Landin-Wilhelmsen, K. (2015). Effect of growth hormone treatment on fractures and quality of life in postmenopausal osteoporosis: A 10-year follow-up study. The Journal of Clinical Endocrinology & Metabolism, 100(9), 3251–3259.Google Scholar
Landin-Wilhelmsen, K., Nilsson, A., Bosaeus, I., & Bengtsson, B. Å. (2003). Growth hormone increases bone mineral content in postmenopausal osteoporosis: A randomized placebo-controlled trial. Journal of Bone and Mineral Research, 18(3), 393–405.CrossRefGoogle ScholarPubMed
Leung, K. C., Doyle, N., Ballesteros, M., Sjogren, K., Watts, C. K. W., Low, T. H., … & Ho, K. K. Y. (2003). Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proceedings of the National Academy of Sciences, 100(3), 1016–1021.Google Scholar
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P., … & Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta analyses of studies that evaluate health care interventions: explanation and elaboration. Annals of Internal Medicine, 151(4), W-65.Google Scholar
Lindsay, R., Silverman, S. L., Cooper, C., Hanley, D. A., Barton, I., Broy, S. B., … & Stracke, H. (2001). Risk of new vertebral fracture in the year following a fracture. The Journal of the American Medical Association, 285(3), 320–323.Google Scholar
Liu, H., Bravata, D. M., Olkin, I., Nayak, S., Roberts, B., Garber, A. M., & Hoffman, A. R. (2007). Systematic review: The safety and efficacy of growth hormone in the healthy elderly. Annals of Internal Medicine, 146(2), 104–115.Google Scholar
Martin, A. R., Sornay-Rendu, E., Chandler, J. M., Duboeuf, F., Girman, C. J., & Delmas, P. D. (2002). The impact of osteoporosis on quality-of-life: The OFELY cohort. Bone, 31(1), 32–36.Google Scholar
McGraw, R. L., & Riggs, J. E. (1994). Osteoporosis, sedentary lifestyle, and increasing hip fractures: Pathogenic relationship or differential survival bias. Calcified Tissue International, 55(2), 87–89.Google Scholar
Mitchell, W. K., Williams, J., Atherton, P., Larvin, M., Lund, J., & Narici, M. (2012). Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Frontiers in Physiology, 3, 1–18.Google Scholar
Nishiyama, K., Sugimoto, T., Kaji, H., Kanatani, M., Kobayashi, T., & Chihara, K. (1996). Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation. Endocrinology, 137(1), 35–41.Google Scholar
Ohlsson, C., Bengtsson, B. A., Isaksson, O. G., Andreassen, T. T., & Slootweg, M. C. (1998). Growth hormone and bone. Endocrine Reviews, 19(1), 55–79.Google Scholar
Palacios, S., Henderson, V. W., Siseles, N., Tan, D., & Villaseca, P. (2010). Age of menopause and impact of climacteric symptoms by geographical region. Climacteric, 13(5), 419–428.Google Scholar
Papadakis, M. A., Grady, D., Black, D., Tierney, M. J., Gooding, G. A., Schambelan, M., & Grunfeld, C. (1996). Growth hormone replacement in healthy older men improves body composition but not functional ability. Annals of Internal Medicine, 124(8), 708–716.Google Scholar
Richelson, L. S., Wahner, H. W., Melton, L. J. III, & Riggs, B. L. (1984). Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. New England Journal of Medicine, 311(20), 1273–1275.Google Scholar
Roemmler, J., Gockel, A., Otto, B., Bidlingmaier, M., & Schopohl, J. (2012). Effects on metabolic variables after 12-month treatment with a new once-a-week sustained-release recombinant growth hormone (GH: LB03002) in patients with GH deficiency. Clinical Endocrinology, 76(1), 88–95.Google Scholar
Rosen, T., Johannsson, G., Johansson, J. O., & Bengtsson, B. Å. (1995). Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. Hormone Research in Paediatrics, 43(1-3), 93–99.Google Scholar
Rothstein, H. R., Sutton, A. J., & Borenstein, M. (2006). Publication bias in meta-analysis. In Rothstein, H. R., Sutton, A. J., & Borenstein, M. (Eds.), Publication bias in meta-analysis: Prevention, assessment, and adjustments (pp. 1–7). West Sussex, ENG: Wiley.Google Scholar
Rudman, D., Feller, A. G., Nagraj, H. S., Gergans, G. A., Lalitha, P. Y., Goldberg, A. F., … & Mattson, D. E. (1990). Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, 323(1), 1–6.Google Scholar
Saaf, M., Hilding, A., Thorén, M., Troell, S., & Hall, K. (1999). Growth hormone treatment of osteoporotic postmenopausal women – A one-year placebo-controlled study. European Journal of Endocrinology, 140(5), 390–399.Google Scholar
Sànchez-Riera, L., Wilson, N., Kamalaraj, N., Nolla, J. M., Kok, C., Li, Y., … & March, L. (2010). Osteoporosis and fragility fractures. Best Practice & Research Clinical Rheumatology, 24(6), 793–810.CrossRefGoogle ScholarPubMed
Syed, Z., & Khan, A. (2002). Bone densitometry: Applications and limitations. Journal of Obstetrics & Gynaecology Canada, 24(6), 476–484.Google Scholar
Takala, J., Ruokonen, E., Webster, N. R., Nielsen, M. S., Zandstra, D. F., Vundelinckx, G., & Hinds, C. J. (1999). Increased mortality associated with growth hormone treatment in critically ill adults. New England Journal of Medicine, 341(11), 785–792.Google Scholar
Viidas, U., Johannsson, G., Mattsson-Hultén, L., & Ahlmén, J. (2003). Lipids, blood pressure and bone metabolism after growth hormone therapy in elderly hemodialysis patients. Journal of Nephrology, 16(2), 231–237.Google Scholar
Welle, S., Thornton, C., Statt, M., & McHenry, B. (1996). Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. The Journal of Clinical Endocrinology & Metabolism, 81(9), 3239–3243.Google Scholar
Wüster, C., Slenczka, E., & Ziegler, R. (1991). Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: Need for additional growth hormone substitution? Klinische Wochenschrift, 69(16), 769–773.Google Scholar
Yarasheski, K. E., Campbell, J. A., & Kohrt, W. M. (1997). Effect of resistance exercise and growth hormone on bone density in older men. Clinical Endocrinology, 47(2), 223–229.Google Scholar
Xu, X., Bennett, S., Ingram, R., & Sonntag, W. (1995). Decreases in growth hormone receptor signal transduction contribute to the decline in insulin-like growth factor I gene expression with age. Endocrinology, 136(10), 4551–4557.Google Scholar
Supplementary material: File

Atkinson supplementary material S1

Online Appendix

Download Atkinson supplementary material S1(File)
File 24.1 KB
Supplementary material: File

Atkinson supplementary material S2

Online Appendix

Download Atkinson supplementary material S2(File)
File 65 KB