IGF-I and pamidronate increase bone mineral density in ovariectomized adult rats

1993 ◽  
Vol 265 (5) ◽  
pp. E770-E776 ◽  
Author(s):  
P. Ammann ◽  
R. Rizzoli ◽  
K. Muller ◽  
D. Slosman ◽  
J. P. Bonjour
Keyword(s):  
Bone Mineral Density ◽  
Cortical Bone ◽  
Bone Mineral ◽  
Mineral Density ◽  
Adult Rats ◽  
Igf I ◽  
Midshaft Tibia ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Ovariectomized Adult Rats

Effects induced by insulin-like growth factor I (IGF-I) and/or the bisphosphonate pamidronate (APD) on bone mineral density (BMD) of the lumbar spine and proximal and midshaft tibia were studied in adult rats made osteopenic by ovariectomy, using dual-energy X-ray absorptiometry. IGF-I, which was administered by osmotic minipumps implanted subcutaneously for 6 wk, caused a dose-dependent increase of BMD at the three investigated sites. A 4-wk course of IGF-I, followed by intermittent cyclical APD administration, induced significant increases of BMD at the levels of spine and proximal tibia. At midshaft tibia, where cortical bone predominates, BMD was increased by IGF-I only. In conclusion, IGF-I increased BMD at sites with trabecular and/or cortical bone, whereas the APD influence was mainly detectable in the former site only.

scholarly journals Conditional disruption of IGF-I gene in type 1α collagen-expressing cells shows an essential role of IGF-I in skeletal anabolic response to loading

2011 ◽  
Vol 301 (6) ◽  
pp. E1191-E1197 ◽  
Author(s):  
Chandrasekhar Kesavan ◽  
Jon E. Wergedal ◽  
K.-H. William Lau ◽  
Subburaman Mohan
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Mechanical Strain ◽  
Bone Size ◽  
Size Difference ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Bone Response ◽  
Igf I ◽  
I Gene

To establish a causal role for locally produced IGF-I in the mechanical strain response in the bone, we have generated mice with conditional disruption of the insulin-like growth factor (IGF) I gene in type 1α2 collagen-expressing cells using the Cre-loxP approach. At 10 wk of age, loads adjusted to account for bone size difference were applied via four-point bending or axial loading (AL) in mice. Two wk of bending and AL produced significant increases in bone mineral density and bone size at the middiaphysis of wild-type (WT), but not knockout (KO), mice. In addition, AL produced an 8–25% increase in trabecular parameters (bone volume-tissue volume ratio, trabecular thickness, and trabecular bone mineral density) at the secondary spongiosa of WT, but not KO, mice. Histomorphometric analysis at the trabecular site revealed that AL increased osteoid width by 60% and decreased tartrate-resistance acidic phosphatase-labeled surface by 50% in the WT, but not KO, mice. Consistent with the in vivo data, blockade of IGF-I action with inhibitory IGF-binding protein (IGFBP4) in vitro completely abolished the fluid flow stress-induced MC3T3-E1 cell proliferation. One-way ANOVA revealed that expression levels of EFNB1, EFNB2, EFNA2, EphB2, and NR4a3 were different in the loaded bones of WT vs. KO mice and may, in part, be responsible for the increase in bone response to loading in the WT mice. In conclusion, IGF-I expressed in type 1 collagen-producing bone cells is critical for converting mechanical signal to anabolic signal in bone, and other growth factors cannot compensate for the loss of local IGF-I.

scholarly journals Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences

2005 ◽  
Vol 185 (3) ◽  
pp. 415-420 ◽  
Author(s):  
S Mohan ◽  
D J Baylink
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Individual Variation ◽  
Normal Population ◽  
Quantitative Computed Tomography ◽  
Control Group ◽  
Mineral Density ◽  
Peak Bone Mineral Density ◽  
Igf I ◽  
Peak Bmd

Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/−) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/− mice (n=18–20 per group). Serum IGF-I was decreased by 23% (P<0.001) in mice with IGF-I haploinsufficiency (+/−) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0.001) and 12% respectively in the IGF-I (+/−) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0.01) and total volumetric BMD (5%, P<0.05) were decreased significantly in the +/− group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0.55) and periosteal circumference (r=0.66) in the pooled data from the +/+ and +/− groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population.

scholarly journals Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in adult rats with collagen-induced arthritis

2003 ◽  
Vol 48 (6) ◽  
pp. 1732-1741 ◽  
Author(s):  
Itsuro Yamane ◽  
Hiroshi Hagino ◽  
Toru Okano ◽  
Makoto Enokida ◽  
Daisuke Yamasaki ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Mineral Density ◽  
Collagen Induced Arthritis ◽  
Adult Rats ◽  
Minodronic Acid

Treatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density

2009 ◽  
Vol 10 (9) ◽  
pp. 1352-1358 ◽  
Author(s):  
Harold N. Rosen ◽  
Vicki Chen ◽  
Antonio Cittadini ◽  
Susan L. Greenspan ◽  
Pamela S. Douglas ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mineral Content ◽  
Bone Mineral ◽  
Mineral Content ◽  
Mineral Density ◽  
Growing Rats ◽  
Igf I

scholarly journals A Metabolic Screen in Adolescents Reveals an Association Between Circulating Citrate and Cortical Bone Mineral Density

2019 ◽  
Vol 34 (7) ◽  
pp. 1306-1313 ◽  
Author(s):  
John P Kemp ◽  
Adrian Sayers ◽  
William D Fraser ◽  
George Davey Smith ◽  
Mika Ala‐Korpela ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Cortical Bone ◽  
Bone Mineral ◽  
Mineral Density ◽  
Cortical Bone Mineral Density

scholarly journals Liver-Derived IGF-I Contributes to GH-Dependent Increases in Lean Mass and Bone Mineral Density in Mice with Comparable Levels of Circulating GH

2011 ◽  
Vol 25 (7) ◽  
pp. 1223-1230 ◽  
Author(s):  
Sarah M. Nordstrom ◽  
Jennifer L. Tran ◽  
Brandon C. Sos ◽  
Kay-Uwe Wagner ◽  
Ethan J. Weiss
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Lean Mass ◽  
Janus Kinase ◽  
Mineral Density ◽  
Gh Secretion ◽  
Igf I ◽  
And Control ◽  
Spleen Mass ◽  
Feedback Pathway

Abstract The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.

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