scholarly journals Concentration of Insulin-Like Growth Factor (IGF)-I and -II in Iliac Crest Bone Matrix from Pre- and Postmenopausal Women: Relationship to Age, Menopause, Bone Turnover, Bone Volume, and Circulating IGFs1

1998 ◽  
Vol 83 (7) ◽  
pp. 2331-2337 ◽  
Author(s):  
Thomas Seck ◽  
Beate Scheppach ◽  
Stefan Scharla ◽  
Ingo Diel ◽  
Werner F. Blum ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Iliac Crest ◽  
Bone Matrix ◽  
Bone Volume ◽  
Human Bone ◽  
Age Related ◽  
Igf I ◽  
The Mean

Insulin-like growth factor-I (IGF-I) and -II are important local regulators of bone metabolism, but their role as determinants of human bone mass is still unclear. In the present study, we analyzed the concentration of IGF-I and -II in the bone matrix of 533 human biopsies from the iliac crest that were obtained during surgery for early breast cancer. There was an inverse association of bone matrix IGF-I concentration with age that was unaffected by menopause. Bone matrix IGF-I was positively associated with histomorphometric and biochemical parameters of bone formation and bone resorption and with cancellous bone volume. Based on the estimates of the linear regression analysis, women with a bone matrix IGF-I concentration 2 sd above the mean had a 20% higher bone volume than women with a bone matrix IGF-I concentration 2 sd below the mean. In contrast, serum IGF-I was neither correlated with bone turnover nor with bone volume and was only weakly associated with bone matrix IGF-I when adjusted for the serum concentration of IGF binding protein-3. Bone matrix IGF-II was positively associated with the osteoblast surface, but in contrast to IGF-I, tended to be positively associated with age and was unrelated to cancellous bone volume. In summary, our study suggests the following. 1) The concentration of IGF-I in cancellous bone undergoes age-related decreases that are similar to those of circulating IGF-I. 2) Menopause has no effect on this age-related decline. 3) Physiological differences in bone matrix IGF-I are associated with differences in iliac crest cancellous bone volume. 4) Bone matrix IGF-I is a better predictor of cancellous bone volume than circulating IGF-I. 5) The role of IGF-II in human bone tissue is clearly distinct from that of IGF-I.

scholarly journals Influence of fluor salts, hormone replacement therapy and calcitonin on the concentration of insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor-beta 1 in human iliac crest bone matrix from patients with primary osteoporosis

2004 ◽  
pp. 81-91 ◽  
Author(s):  
CE Pepene ◽  
T Seck ◽  
I Diel ◽  
HW Minne ◽  
R Ziegler ◽  
...  
Keyword(s):  
Hormone Replacement Therapy ◽  
Growth Factor ◽  
Bone Turnover ◽  
Replacement Therapy ◽  
Iliac Crest ◽  
Transforming Growth Factor ◽  
Hormone Replacement ◽  
Bone Matrix ◽  
Primary Osteoporosis ◽  
Igf I

OBJECTIVE: Data from cell culture experiments suggest that local growth factors (GFs) may mediate the effects of estrogens, calcitonin or fluor ions on the skeleton. To assess the in vivo relevance of the in vitro reports, the effect of fluor salts, hormone replacement therapy (HRT) and calcitonin on the concentrations of IGF-I, IGF-II and transforming growth factor (TGF)-beta 1 in bone matrix extracts from osteoporotic patients was evaluated. DESIGN: Iliac crest bone biopsies were obtained from 170 patients (76 men and 94 women) with primary osteoporosis aged 55.5+/-0.8 Years. METHODS: Bone matrix extraction was performed based on a guanidine-HCl/ethylendiamine-tetra-acetic acid method. RESULTS: In comparison with age- and body mass index (BMI)-matched controls, no influence of long-term therapy with fluor ions (n=41) or calcitonin (n=16) on the bone matrix concentration of GFs was noticed. Postmenopausal women with osteoporosis on HRT (n=39) had lower skeletal IGF-I but not IGF-II levels as compared with age- and BMI-matched non-users. However, the lower rate of bone turnover in women with HRT may account for this difference, since the significance was lost after adjustment for alkaline phosphatase. Likewise, a tendency for lower TGF-beta 1 levels was observed in HRT users as compared with non-users but was lost after adjustment for bone turnover. None of the therapies influenced the serum levels of GFs when patients receiving continuous therapy for at least 1 Year before bone biopsy were considered. CONCLUSIONS: Our data suggest no direct effect of fluor therapy on skeletal GFs levels. At the concentrations used, neither HRT nor calcitonin appeared to exert any significant influence on serum or bone matrix GF levels.

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.

Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I in rats

1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Rank Order ◽  
Insulin Like Growth Factor ◽  
Plasma Binding ◽  
Factor I ◽  
Igf I ◽  
The Mean ◽  
Growth Factor I ◽  
Sites Of Action

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204

scholarly journals Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Mass Density ◽  
Female Rats ◽  
Bone Mass Density ◽  
Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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