The effects of recombinant human insulin-like growth factor (rhIGF)-1 and rhIGF-1/IGF binding protein-3 administration on rat osteopenia induced by ovariectomy with concomitant bilateral sciatic neurectomy.
We compared the effect of administration of recombinant human insulin-like growth factor-1 (rhIGF-1) alone or the rhIGF-1/IGF binding protein-3 (IGFBP-3) complex on osteopenia in rats. Female Sprague-Dawley rats (8 months old) underwent combined ovariectomy and bilateral sciatic neurectomy (OVX-NX) or sham operation only. After 2 months, the OVX-NX animals were injected subcutaneously with rhIGF-1 alone or with rhIGF-1A IGFBP-3 equimolar complex for 4 weeks. The IGF-1 contents and dose were 0.3 mg/kg of body weight (BW) three times/week, 3 mg/kg of BW once/week, or 3 mg/kg of BW three times /week. At the end of the experiment, the 4th and 5th lumbar vertebrae (L4, L5) and the proximal tibiae were removed after tetracycline labeling, and histomorphometrical analyses were performed on undecalcified sections using Villanueva's staining. The cancellous bone volume at L5 significantly increased by thickening of the trabecular width in rats treated with the complex. However, the increase in the values at the proximal tibia was not significant. The bone formation rates (BFR/BS) in the lumbar vertebrae of rats treated with the complex three times a week at doses of 0.3 mg/kg of BW and 3 mg/kg of BW were both significantly increased but the parameter increase was less marked with the dose of 3 mg/kg of BW once/week. The BFR/BS did not increase significantly in animals treated with IGF-1 alone. These findings clearly demonstrated that the effect of systemically administered rhIGF-1 on bone formation was markedly potentiated when combined with IGFBP-3 in estrogen deficiency combined with reduced activity. The action of IGF-1 was less potent on the bone in paralyzed limbs. The action of rhIGF-1/IGFBP-3 on trabecular bone appeared to depend not only on the dose but also on the frequency of administration and the parts of the skeleton in rats.
Narusawa
K
K
Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nakamura
T
T
Suzuki
K
K
Matsuoka
Y
Y
Lee
L J
LJ
Tanaka
H
H
Seino
Y
Y
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001846:Bone Development / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000254:growth & development; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000502:physiology / Q000601:surgery; D013977:Tibia / Q000187:drug effects* / Q000254:growth & development
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I