Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats

1994 ◽  
Vol 267 (1) ◽  
pp. E1-E6 ◽  
Author(s):  
K. Mueller ◽  
R. Cortesi ◽  
D. Modrowski ◽  
P. J. Marie
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Ovariectomized Rats ◽  
Maximal Effect ◽  
Insulin Like Growth Factor ◽  
Bone Formation Rate ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Although in vitro experiments indicate that insulin-like growth factor I (IGF-I) is an anabolic hormone in bone cell metabolism, the effects of IGF-I in vivo on bone formation are unclear. We thus investigated whether IGF-I is able to stimulate bone formation in adult rats with established osteopenia induced by ovariectomy (OVX). IGF-I was administered at daily doses of 0.05, 0.2, and 0.8 mg/kg for 3 wk. OVX induced a marked osteopenia in femur and tibia. Administration of IGF-I increased trabecular bone mass with a maximal effect at 0.2 mg/kg. The same dose stimulated bone formation, as revealed by an increase in osteoid surface, osteoblast surface, triple tetracycline-labeled surface, and bone formation rate. The mineral apposition rate was equally stimulated at all doses. At the highest dose, IGF-I increased osteoclast surface and osteoclast number. These data indicate that, in the adult OVX rat, IGF-I stimulates bone formation and increases trabecular bone volume at medium doses and enhances the histological indexes of bone resorption at high doses.

scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.

Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats

1994 ◽  
Vol 130 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Katharina Binz ◽  
Christoph Schmid ◽  
Roger Bouillon ◽  
E Rudolf Froesch ◽  
Kay Jürgensen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Density ◽  
Trabecular Bone ◽  
Mineral Metabolism ◽  
Male Rats ◽  
Insulin Like Growth Factor ◽  
Trabecular Bone Density ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Binz K, Schmid C, Bouillon R, Froesch ER, Jürgensen K, Hunziker EB. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur J Endocrinol 1994;130:387–93. ISSN 0804–4643 Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 μg/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters. We conclude that IGF I-infusion in male rats treated with high doses of dexamethasone reduces insulin resistance and restores calcitriol production but not osteoblast function or responsiveness to calcitriol. K Binz, Division de Diabétologie, Hôpital Cantonal Universitaire, 1211 Geneva, Switzerland

scholarly journals Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading

2007 ◽  
Vol 103 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Benjamin M. Boudignon ◽  
Daniel D. Bikle ◽  
Pam Kurimoto ◽  
Hashem Elalieh ◽  
Shigeki Nishida ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Weight Bearing ◽  
Bone Volume ◽  
Insulin Like Growth Factor ◽  
Skeletal Unloading ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

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.

In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats

Bone ◽  
1991 ◽  
Vol 12 (1) ◽  
pp. 21-26 ◽  
Author(s):  
E.M. Spencer ◽  
C.C. Liu ◽  
E.C.C. Si ◽  
G.A. Howard
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation

1995 ◽  
Vol 268 (2) ◽  
pp. E318-E327 ◽  
Author(s):  
J. M. Lean ◽  
C. J. Jagger ◽  
T. J. Chambers ◽  
J. W. Chow
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Mechanical Stimulation ◽  
Matrix Protein ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Osteogenic Response ◽  
Igf I ◽  
Growth Factor I

We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13-wk-old rats. We used this model to relate the kinetics of the bone-forming response, as measured by administration of fluorescent markers, to an in situ hybridization analysis of changes in mRNA for two matrix proteins (type I collagen and osteocalcin) and a growth factor implicated in the regulation of bone formation [insulin-like growth factor I (IGF-I). We found that increased fluorochrome labeling was accompanied by an increase in the proportion of trabecular bone surfaces on which transcripts for collagen type I and osteocalcin were detectable, from < 3 to 25% 72 h after loading. IGF-I expression on trabecular surfaces showed a slightly earlier increase. We also noted intense hybridization for IGF-I in osteocytes in the diaphyseal cortex and in metaphyseal trabeculae. This was observed only in loaded bones, within 6 h of loading, and became undetectable in trabecular osteocytes 48 h and cortical osteocytes 120 h after loading. This is the first identification of a specific mRNA species in osteocytes after mechanical stimulation. Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF-I, in the osteogenic response of bone to mechanical stimulation.

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