Journal of Applied Physiology Journal of Neurophysiology
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J Appl Physiol 103: 125-131, 2007. First published April 5, 2007; doi:10.1152/japplphysiol.00111.2007
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Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading

Benjamin M. Boudignon,1 Daniel D. Bikle,1 Pam Kurimoto,1 Hashem Elalieh,1 Shigeki Nishida,1 Yongmei Wang,1 Andrew Burghardt,2 Sharmila Majumdar,2 Benjamin E. Orwoll,1 Clifford Rosen,3 and Bernard P. Halloran1

1Division of Endocrinology, Veterans Affairs Medical Center, and Department of Medicine and 2Department of Radiology, University of California, San Francisco, California; and 3Department of Medicine, Maine Center for Osteoporosis Research, Bangor, Maine

Submitted 24 January 2007 ; accepted in final form 3 April 2007

IGF-I stimulates osteoblast proliferation, bone formation, and increases bone volume in normal weight-bearing animals. During skeletal unloading or loss of weight bearing, bone becomes unresponsive to the anabolic effects of insulin-like growth factor I (IGF-I). To determine whether skeletal reloading after a period of unloading increases bone responsiveness to IGF-I, we examined bone structure and formation in response to IGF-I under different loading conditions. Twelve-week-old rats were divided into six groups: loaded (4 wk), unloaded (4 wk), and unloaded/reloaded (2/2 wk), and treated with IGF-I (2.5 mg·kg–1·day–1) or vehicle during the final 2 wk. Cortical bone formation rate (BFR), cancellous bone volume and architecture in the secondary spongiosa (tibia and vertebrae), and total volume and calcified volume in the primary spongiosa (tibia) were assessed. Periosteal BFR decreased during unloading, remained low during reloading in the vehicle-treated group, but was dramatically increased in IGF-I-treated animals. Cancellous bone volume decreased with unloading and increased with reloading, but the effect was exaggerated in the tibia of IGF-I-treated animals. Total and calcified volumes in the primary spongiosa decreased during unloading in the vehicle-treated animals. IGF-I treatment prevented the loss in volume. These data show that reloading after a period of skeletal unloading increases bone responsiveness to IGF-I, and they suggest that IGF-I may be of therapeutic use in patients who have lost bone as a consequence of prolonged skeletal disuse.

reloading; micro-computed tomograhy; osteopenia; weight bearing



Address for reprint requests and other correspondence: B. P. Halloran, Veterans Affairs Medical Center (111N), 4150 Clement St., San Francisco, CA 94121 (e-mail: bernard.halloran{at}ucsf.edu)







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