Original Article

Growth hormone protects against ovariectomy-induced bone loss in states of low circulating insulin-like growth factor (IGF-1)

J Christopher Fritton 1, Kelly B Emerton 1, Hui Sun 2, Yuki Kawashima 2, Wilson Mejia 2, Yingjie Wu 2, Clifford J Rosen 3, David Panus 4, Mary Bouxsein 4, Robert J Majeska 1, Mitchell B Schaffler 1, Shoshana Yakar 2 *

1Leni & Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY, USA 2Department of Medicine, Division of Endocrinology, Diabetes & Bone Disease, Mount Sinai School of Medicine, New York, NY, USA 3Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, USA 4Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

email: Shoshana Yakar (shoshana.yakar@mssm.edu)

^*Correspondence to Shoshana Yakar, Assistant Professor, Endocrinology/Diabetes and Bone Disease, The Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1055, New York, NY 10029, USA.

This work was presented in part at the 30th Annual Meeting of the American Society of Bone and Mineral Research, September 12-16, 2008, Montreal, Quebec, Canada.

Keywords

growth factors • estrogen • apoptosis • remodeling • osteoporosis

Abstract

Early after estrogen loss in postmenopausal women and ovariectomy (OVX) of animals, accelerated endosteal bone resorption leads to marrow expansion of long bone shafts that reduce mechanical integrity. Both growth hormone (GH) and insulin-like growth factor (IGF-1) are potent regulators of bone remodeling processes. To investigate the role of the GH/IGF-1 axis with estrogen deficiency, we used the liver IGF-1-deficient (LID) mouse. Contrary to deficits in controls, OVX of LID mice resulted in maintenance of cortical bone mechanical integrity primarily owing to an enhanced periosteal expansion affect on cross-sectional structure (total area and cortical width). The serum balance in LID that favors GH over IGF-1 diminished the effects of ablated ovarian function on numbers of osteoclast precursors in the marrow and viability of osteocytes within the cortical matrix and led to less endosteal resorption in addition to greater periosteal bone formation. Interactions between estrogen and the GH/IGF-1 system as related to bone remodeling provide a pathway to minimize degeneration of bone tissue structure and osteoporotic fracture. © 2010 American Society for Bone and Mineral Research

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Received: 3 March 2009; Revised: 5 May 2009; Accepted: 6 July 2009

Digital Object Identifier (DOI)

10.1359/jbmr.090723  About DOI