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·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.

Download Full-text

Skeletal Unloading Induces Resistance to Insulin-Like Growth Factor-I (IGF-I) by Inhibiting Activation of the IGF-I Signaling Pathways

Journal of Bone and Mineral Research ◽

10.1359/jbmr.0301241 ◽

2003 ◽

Vol 19 (3) ◽

pp. 436-446 ◽

Cited By ~ 76

Author(s):

Takeshi Sakata ◽

Yongmei Wang ◽

Bernard P Halloran ◽

Hashem Z Elalieh ◽

Jay Cao ◽

...

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Insulin Like Growth Factor ◽

Skeletal Unloading ◽

Factor I ◽

Igf I ◽

Resistance To Insulin ◽

Growth Factor I

Download Full-text

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.1.4484 ◽

1998 ◽

Vol 83 (1) ◽

pp. 81-87 ◽

Cited By ~ 1

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.

Download Full-text

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.1.e1 ◽

1994 ◽

Vol 267 (1) ◽

pp. E1-E6 ◽

Cited By ~ 1

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.

Download Full-text

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

Bone ◽

10.1016/8756-3282(91)90050-s ◽

1991 ◽

Vol 12 (1) ◽

pp. 21-26 ◽

Cited By ~ 163

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

Download Full-text

Matrix Concentration of Insulin-like Growth Factor I (IGF-I) is Negatively Associated with Biomechanical Properties of Human Tibial Cancellous Bone Within Individual Subjects

Calcified Tissue International ◽

10.1007/s00223-004-0140-y ◽

2005 ◽

Vol 77 (1) ◽

pp. 37-44 ◽

Cited By ~ 5

Author(s):

X. N. Dong ◽

Y. N. Yeni ◽

B. Zhang ◽

C. M. Les ◽

G. J. Gibson ◽

...

Keyword(s):

Growth Factor ◽

Cancellous Bone ◽

Biomechanical Properties ◽

Insulin Like Growth Factor ◽

Negatively Associated ◽

Factor I ◽

Igf I ◽

Growth Factor I ◽

Matrix Concentration

Download Full-text

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.2.e318 ◽

1995 ◽

Vol 268 (2) ◽

pp. E318-E327 ◽

Cited By ~ 23

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.

Download Full-text