Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women.
Because insulin-like growth factor I (IGF-I) is a potent stimulator of osteoblast proliferation, it has potential in the treatment of osteoporosis. However, IGF-I affects multiple organ systems, and it is unclear whether treatment can stimulate bone formation without producing unacceptable side effects. Therefore, we evaluated the effects of treatment with recombinant human IGF-I in 18 postmenopausal women who received various dosages (30, 60, 120, or 180 micrograms/kg.day) by sc injections for 6 days. Serum IGF-I concentrations increased by 2- to 4-fold during treatment. There were dose-dependent increases in serum type I procollagen carboxyl-terminal propeptide concentration (r = 0.85, P < 0.001), an index of collagen synthesis, and of urinary excretion of deoxypyridinoline (r = 0.75, P = 0.001), an index of bone collagen breakdown. At the two higher dosages, recombinant human IGF-I caused orthostatic hypotension, sinus tachycardia, bilateral parotid discomfort, weight gain, and edema in some women. Hypoglycemia did not occur. However, treatment at the 2 lower dosages increased serum type I procollagen carboxyl-terminal propeptide significantly and produced minimal or no side effects. Long-term studies on the effects and the safety of low dosage recombinant human IGF-I on bone mass should now be undertaken in osteoporotic women.
Ebeling
P R
PR
Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota 55905.
Jones
J D
JD
O'Fallon
W M
WM
Janes
C H
CH
Riggs
B L
BL
D000368:Aged; D000596:Amino Acids / Q000652:urine; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins; D012016:Reference Values; D013997:Time Factors
D000596:Amino Acids; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C042813:procollagen type I carboxy terminal peptide; D007334:Insulin-Like Growth Factor I; C036020:deoxypyridinoline