Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading.
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 x kg(-1) x 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.
Boudignon
Benjamin M
BM
Division of Endocrinology, Veterans Affairs Medical Center, and Department of Medicine, University of California, San Francisco, California, USA.
Bikle
Daniel D
DD
Kurimoto
Pam
P
Elalieh
Hashem
H
Nishida
Shigeki
S
Wang
Yongmei
Y
Burghardt
Andrew
A
Majumdar
Sharmila
S
Orwoll
Benjamin E
BE
Rosen
Clifford
C
Halloran
Bernard P
BP
D000818:Animals; D015519:Bone Density; D001861:Bone Regeneration / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005360:Fibula / Q000378:metabolism / Q000503:physiopathology; D019417:Hindlimb Suspension; D006811:Humerus / Q000378:metabolism / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000378:metabolism / Q000503:physiopathology; D013977:Tibia / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016474:Weight-Bearing
D007334:Insulin-Like Growth Factor I