Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women.

Abstract

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.

Identification of Bioactive Molecules by Adipogenesis Profiling of Organic Compounds

“…Deficiency in IGF1, a prominent member of IGFs, is suggested to be a cause of decrease in bone density with aging (20,21), and administration of IGF1 prevents the decrease of bone density in osteoporosis patients in part by stimulating osteogenesis (22)(23)(24). The high homology between IGF1 and insulin suggested that the osteogenesis-enhancing activity of IGF1 may be mimicked by the chemicals that potentiated the insulin-induced adipogenesis.…”

Dose-dependent effects of combined IGF-I and TGF-β1 application in a sheep cervical spine fusion model

“…However, both authors also determined nearly similar osteoinductive effects of TGF-β1 in a wide range of concentrations [13,39]. Additionally, Ebeling et al [10] demonstrated analogous effects of four different doses of IGF-I on bone turnover in normal women. Although dose-dependent effects for isolated IGF-I and TGF-β1 application are sufficiently documented, to our knowledge, no study has been performed to determine whether a dose-dependent effect of combined IGF-I and TGF-β1 application on bone matrix formation exists.…”

The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective

“…Information on the effects of growth factor therapy on older people is limited to that from two studies using rhIGF-I. The results with low-dose rhIGF-I reported by Ebeling et al [31] and Ghiron et al [37] provided biochemical evidence for increased bone formation activity with minimal increased resorption. However, the effects of rhIGF-I and rhTGF␤ on bone mass and fracture occurrence in older people have not yet been reported nor have optimal dosage schedules been established.…”

“…In a study involving 18 postmenopausal women (mean age 66 years), Ebeling et al evaluated the effects of various dosages of subcutaneous rhIGF-I (30, 60, 120 or 180 g/kg/day) for 6 days [31]. Serum IGF-I concentrations increased two-to fourfold during treatment.…”