Growth hormone protects against ovariectomy-induced bone loss in states of low circulating insulin-like growth factor (IGF-1).
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.
Fritton
J Christopher
JC
Leni & Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Emerton
Kelly B
KB
Sun
Hui
H
Kawashima
Yuki
Y
Mejia
Wilson
W
Wu
Yingjie
Y
Rosen
Clifford J
CJ
Panus
David
D
Bouxsein
Mary
M
Majeska
Robert J
RJ
Schaffler
Mitchell B
MB
Yakar
Shoshana
S
D050154:Adiposity; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000378:metabolism* / Q000517:prevention & control; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D005269:Femur / Q000033:anatomy & histology; D005434:Flow Cytometry; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D010052:Ovariectomy
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone