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 Sibling Pair Linkage and Association Studies between Peak Bone Mineral Density and the Gene Locus for the Osteoclast-Specific Subunit (OC116) of the Vacuolar Proton Pump on Chromosome 11p12-13

2002 ◽  
Vol 87 (8) ◽  
pp. 3819-3824 ◽  
Author(s):  
Gwenaelle Carn ◽  
Daniel L. Koller ◽  
Munro Peacock ◽  
Siu L. Hui ◽  
Wayne E. Evans ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Femoral Neck ◽  
Bone Mineral ◽  
Proton Pump ◽  
Autosomal Recessive ◽  
Chromosomal Region ◽  
Mineral Density ◽  
Peak Bone Mineral Density ◽  
Peak Bmd ◽  
Vacuolar Proton Pump

A major determinant of the risk of osteoporosis is peak bone mineral density (BMD), which has been shown to have substantial heritability. The genes for 3 BMD-related phenotypes (autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessives osteopetrosis) are all in the chromosome 11q12-13 region. We reported linkage of peak BMD in a large sample of healthy premenopausal sister pairs to this same chromosomal region, suggesting that the genes underlying these 3 disorders may also play a role in determining peak BMD within the normal population. To test this hypothesis, we examined the gene responsible for 1 form of autosomal recessive osteopetrosis, TCIRG1, which encodes an osteoclast-specific subunit (OC116) of the vacuolar proton pump. We identified 3 variants in the sequence of TCIRG1, but only one, single nuclear polymorphism 906713, had sufficient heterozygosity for use in genetic analyses. Our findings were consistent with linkage to femoral neck BMD, but not to spine BMD, in a sample of 995 healthy premenopausal sister pairs. However, further analysis, using both population and family-based disequilibrium approaches, did not demonstrate any evidence of association between TCIRG1 and the spine or femoral neck BMD. Therefore, our linkage data suggest that the chromosomal region that contains OC116 harbors a gene that affects peak BMD, but our association results indicate that polymorphisms in the OC116 gene do not affect peak BMD.

The Effect of Hormonal Oral Contraception on Acquisition of Peak Bone Mineral Density of Adolescents and Young Women

2012 ◽  
Vol 25 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Susan Ziglar ◽  
Tracy S. Hunter
Keyword(s):  
Bone Mineral Density ◽  
Bone Mass ◽  
Bone Mineral ◽  
Young Women ◽  
Bone Mineralization ◽  
Critical Time ◽  
Health Concern ◽  
Mineral Density ◽  
Peak Bone Mineral Density ◽  
Bone Mass Accrual

Maximizing bone mass in youth is touted as the best strategy to offset the natural losses of aging and the menopausal transition. Not achieving maximum peak bone mineral density (BMD) is an independent risk factor for osteoporosis and thus a public health concern. Adolescence is a critical time of bone mineralization mediated by endogenous estradiol. Research has shown that the highest velocity of bone mass accrual occurs 1 year before menarche and after the first 3 years. Low-peak attainment of BMD in young women is associated with contributing factors such as diets low in calcium, eating disorders, lack of exercise, smoking, and low estrogen states. Oral contraceptives (OCs) suppress endogenous estradiol production by suppressing the hypothalamic–pituitary–ovarian axis. Thus, OCs, by replacing endogenous estradiol with ethinyl estradiol (EE), establish and maintain new hormone levels. The early initiation and the use of very low dose of EE raises the possibility that bone mass accrual at a critical time of bone mineralization in young women or adolescents may be jeopardized. This review examines the studies of BMD in adolescents and young women that use combination hormonal contraception. Some studies had inherent limitations, such as small trial, poor control of confounders, failure to exclude women with prior use of hormonal contraceptives, or prior pregnancy from control groups. The vast majority of reviewed studies showed OCs containing 20 to 30 µg of EE interfere with acquisition of peak BMD. Limited numbers of studies examine the effects of OCs containing 35 µg on adolescents and young adults. Additionally, studies are needed evaluating the progestin component of OCs as their differing androgenic properties may affect bone mineralization as well.

scholarly journals Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
A. Sánchez ◽  
L. R. Brun ◽  
H. Salerni ◽  
P. R. Costanzo ◽  
D. González ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Control Group ◽  
Bone Resorption Marker ◽  
Similar Response ◽  
Mineral Density ◽  
Turnover Markers

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab.Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

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 Experimental investigation of bone mineral density in Thoroughbreds using quantitative computed tomography

2015 ◽  
Vol 26 (3) ◽  
pp. 81-87 ◽  
Author(s):  
Kazutaka YAMADA ◽  
Fumio SATO ◽  
Tohru HIGUCHI ◽  
Kaori NISHIHARA ◽  
Mitsunori KAYANO ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Mineral Density ◽  
Experimental Investigation ◽  
Bone Mineral ◽  
Quantitative Computed Tomography ◽  
Mineral Density

scholarly journals Role of Dietary Intake and Serum 25(OH)D on the Effects of a Multicomponent Exercise Program on Bone Mass and Structure of Frail and Pre-Frail Older Adults

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3016
Author(s):  
Ana Moradell ◽  
David Navarrete-Villanueva ◽  
Ángel I. Fernández-García ◽  
Jorge Marín-Puyalto ◽  
Alejandro Gómez-Bruton ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Older Adults ◽  
Dietary Intake ◽  
Bone Mineral ◽  
Bone Structure ◽  
Quantitative Computed Tomography ◽  
Mineral Density ◽  
Frail Older Adults ◽  
Frail Elders ◽  
Tibia Length

The multicomponent training (MCT) effect on bone health in frail and pre-frail elders, which is influenced by dietary intake, is still unknown. The objective of this non-randomized intervention trial was to assess the effects of a 6-month MCT on bone structure in frail and pre-frail elders, and to analyse the influence of dietary intake and serum vitamin D (25(OH)D) in these changes. Thirty MCT (TRAIN) and sixteen controls (CON), frail and pre-frail completed the information required for this study. Peripheral quantitative computed tomography measurements were taken at 4% and 38% of the tibia length and dietary intake was registered. The 25(OH)D values were obtained from blood samples. Analyses of covariance (ANCOVA) for repeated measures showed significant decreases for CON in total bone mineral content at 38% of tibia length. One factor ANOVAs showed smaller decreases in bone mineral density and cortical thickness percentage of change in TRAIN compared to CON. Linear regression analyses were performed to study the influence of nutrients and 25(OH)D on bone changes. Alcohol showed a negative influence on fracture index changes, while polyunsaturated fatty acid and vitamin A showed a positive association with some bone variables. The 25(OH)D only affected positively the cortical bone mineral density. In conclusion, our MCT seems to slow down some of the bone detriments associated with ageing in frail and pre-frail older adults, with alcohol showing a negative effect on the bone and apparent limited effect of nutrients and serum 25(OH)D on training related changes.

scholarly journals Bone mineral density in children with long-term antiepileptic therapy

2013 ◽  
Vol 141 (5-6) ◽  
pp. 329-332 ◽  
Author(s):  
Milena Dimic ◽  
Aleksandar Dimic ◽  
Zoran Milosevic ◽  
Jelena Vojinovic
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Drug Therapy ◽  
Antiepileptic Drug ◽  
Bone Mineral ◽  
Control Group ◽  
Mineral Density ◽  
Antiepileptic Therapy ◽  
Epileptic Children ◽  
Antiepileptic Drug Therapy

Introduction. Vitamin D active metabolites deficit that is altered by negative calcium and phosphorus balance is a potential complication during long?term antiepileptic drug therapy. Objective. The aim of this study was to examine lumbar bone mineral density (BMD) in epileptic children receiving antiepileptic drug therapy longer than one year. methods. The examined sample consisted of 34 epileptic children, 18 male and 16 female, aged 6?12 (9.77?2.01) years, treated with carbamazepine, valproate, phenobarbital, lamotrigine or their combination without vitamin D supplementation. The lumbar spine BMD (L1?L4) was estimated by a Lunar densitometer and obtained results were compared with results of 35 matched population of healthy children from the control group. results. Lumbar BMD Z?score was significantly lower in female patients treated with antiepileptic therapy compared with those in the control group (?1.048?1.35 vs. ?0.399?0.518; p=0.03). Bone mineral density Z?score decrease of both gender groups receiving antiepileptic polytherapy was significantly lower compared to the control group (?1.153?0.938 vs. ?0.043?0.815; p=0.007). Therapy duration had no influence on the lumbar BMD level decrease either in boys (rxy=0.33; p=0.174) or in girls (rxy=0.02; p=0.935) treated with antiepileptic therapy. Conclusion. Our results have indicated that antiepileptic drug therapy usage longer than one year can have adverse affects on the lumbar spine BMD (L1?L4) in epileptic children, and that prophylactic vitamin D supplementation is also necessary in these patients.

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