scholarly journals RAGE supports parathyroid hormone-induced gains in femoral trabecular bone

2010 ◽  
Vol 298 (3) ◽  
pp. E714-E725 ◽  
Author(s):  
Binu K. Philip ◽  
Paul J. Childress ◽  
Alexander G. Robling ◽  
Aaron Heller ◽  
Peter P. Nawroth ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
Bone Mineral ◽  
Cancellous Bone ◽  
Immunoglobulin Superfamily ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Bone Response ◽  
Accrual Rate ◽  
Underlying Mechanisms

Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but significant questions remain as to the underlying mechanisms. The receptor for advanced glycation end products (RAGE) is a multiligand receptor of the immunoglobulin superfamily; however, recent studies indicate a role in bone physiology. We investigated the significance of RAGE to hormone-induced increases in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice with human PTH-(1–34) at 30 μg·kg−1·day−1 or vehicle control, 7 days/wk, for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD) and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH-mediated relative increases in cortical area of the midshaft femur were not compromised in the null mice. However, the hormone-induced gain in femoral cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE impaired PTH-mediated increases in femoral cancellous bone volume, connectivity density, and trabecular number but did not impact increases in trabecular thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral expression of bone formation genes, but their relative PTH-responsiveness was not impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass, with the exception of the spine, and an enhanced accrual rate of fat mass. We conclude that RAGE is necessary for key aspects of the skeleton's response to anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of femoral trabecular architecture but not intrinsically necessary for increasing cortical thickness.

Increased training loads do not magnify cancellous bone gains with rodent jump resistance exercise

2010 ◽  
Vol 109 (6) ◽  
pp. 1600-1607 ◽  
Author(s):  
J. M. Swift ◽  
H. G. Gasier ◽  
S. N. Swift ◽  
M. P. Wiggs ◽  
H. A. Hogan ◽  
...  
Keyword(s):  
Bone Formation ◽  
Resistance Exercise ◽  
Body Mass ◽  
Bone Mineral ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
High Load ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Bone Response

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cancellous bone of the proximal tibia metaphysis (PTM) and femoral neck (FN). Sprague-Dawley rats (male, 6 mo old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or sedentary cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE during 5 wk of training. PTM cancellous volumetric bone mineral density (vBMD), assessed by in vivo peripheral quantitative computed tomography scans, significantly increased in both exercise groups (+9%; P < 0.001), resulting in part from 130% (HRE; P = 0.003) and 213% (LRE; P < 0.0001) greater bone formation (measured by standard histomorphometry) vs. CC. Additionally, mineralizing surface (%MS/BS) and mineral apposition rate were higher (50–90%) in HRE and LRE animals compared with controls. PTM bone microarchitecture was enhanced with LRE, resulting in greater trabecular thickness ( P = 0.03) and bone volume fraction (BV/TV; P = 0.04) vs. CC. Resorption surface was reduced by nearly 50% in both exercise paradigms. Increased PTM bone mass in the LRE group translated into a 161% greater elastic modulus ( P = 0.04) vs. CC. LRE and HRE increased FN vBMD (10%; P < 0.0001) and bone mineral content (∼20%; P < 0.0001) and resulted in significantly greater FN strength vs. CC. For the vast majority of variables, there was no difference in the cancellous bone response between the two exercise groups, although LRE resulted in significantly greater body mass accrual and bone formation response. These results suggest that jumping at minimal resistance provides a similar anabolic stimulus to cancellous bone as jumping at loads exceeding body mass.

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 Effect of 7 Months of Physical Training and Military Routine on the Bone Mass of Young Adults

2019 ◽  
Vol 184 (7-8) ◽  
pp. e353-e359
Author(s):  
Josiel Almeida de Avila ◽  
Mauro Augusto Schreiter Melloni ◽  
Mauro Alexandre Pascoa ◽  
Vagner Xavier Cirolini ◽  
Camila Justino de Oliveira Barbeta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Bone Mass ◽  
Bone Mineral ◽  
Physical Training ◽  
Great Influence ◽  
Small Sample ◽  
Fat Free Mass ◽  
Z Score ◽  
Mineral Density ◽  
Bone Response

Abstract Introduction Physical activity (PA) has a great influence on bone mineral density (BMD) and bone mineral content (BMC), however longitudinal studies that seek to relate bone mass to physical activity are scarce and have a small sample size. The aim of this study was to evaluate and compare the effect of 7 months of military physical training (MPT), impact sports (IS), and swimming in the bone mass of young military adults. Materials and Methods A prospective study was conducted with 213 military school students (male and aged 19.2 ± 1.2 years) divided into three groups: MPT (n = 144), IS (n = 56), and Swimming (n = 13). Dual-energy X-ray absorptiometry was used to determine body composition (percentage of fat, fat mass, and fat-free mass) and bone mass (BMD, BMD Z-Score, total BMC, arm BMC, leg BMC, and trunk BMC), at the beginning of the military service and after 7 months of training. Results It was observed a significant increase in BMD, BMD Z-Score, total BMC and BMC of all segments analyzed for all groups (p < 0.01). There was a significantly greater variation in BMD of the IS group in relation to the MPT group (p < 0.01), and in the arm BMC of the MPT group in relation to the IS group (p < 0.05). Conclusion After 7 months of training, there were significant increases in BMC and BMD of all the groups evaluated. The bone response was associated with the muscular group used in the physical exercise and the IS group showed greater gain in BMD.

scholarly journals Programming Effect of the Parental Obesity on the Skeletal System of Offspring at Weaning Day

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 424
Author(s):  
Radoslaw Piotr Radzki ◽  
Marek Bienko ◽  
Dariusz Wolski ◽  
Monika Ostapiuk ◽  
Pawel Polak ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Mineral ◽  
High Energy ◽  
Diet Group ◽  
Male Rats ◽  
Bending Test ◽  
Male Rat ◽  
Skeletal System ◽  
Mineral Density ◽  
Trabecular Thickness

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.

scholarly journals The Association between Bone Mineral Density and Periodontal Disease in Middle-Aged Adults

2021 ◽  
Vol 18 (6) ◽  
pp. 3321
Author(s):  
Hsin-Hua Chou ◽  
Sao-Lun Lu ◽  
Sen-Te Wang ◽  
Ting-Hsuan Huang ◽  
Sam Li-Sheng Chen
Keyword(s):  
Bone Mineral Density ◽  
Young Adults ◽  
Bone Mass ◽  
Periodontal Disease ◽  
Bone Mineral ◽  
Intervention Program ◽  
Past History ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Periodontal Index

The association between osteoporosis and periodontal disease (PD) has been revealed by previous studies, but there have been few studies on the association in younger adults. We enrolled a total of 7298 adults aged 40 to 44 who underwent PD screening between 2003 and 2008. Data on quantitative ultrasound for the measurement of bone mineral density (BMD) were collected for the diagnostic criteria of osteopenia and osteoporosis. The Community Periodontal Index (CPI) was measured for defining PD. A multiple logistic regression model was used to assess the effect of low bone mass on the risk of PD. Of 7298 enrollees, 31% had periodontal pockets >3 mm, 36.2% had osteopenia, and 2.1% had osteoporosis. The 39.8% of PD prevalence was high in adults with osteoporosis, followed by 33.3% in osteopenia. A negative association was found between BMD and CPI value (p < 0.0001). Low bone mass was associated with the risk of PD (adjusted OR: 1.13; 95% CI:1.02–1.26) after adjusting the confounding factors, including age, gender, education level, overweight, smoking status, past history of osteoporosis, and diabetes mellitus. An association between BMD and PD among young adults was found. An intervention program for the prevention of PD and osteoporosis could be considered starting in young adults.

scholarly journals P114 Effect of vitamin D on parathyroid hormone, serum calcium and bone mineral density in patients with primary hyperparathyroidism being managed conservatively

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Mahrukh Khalid ◽  
Vismay Deshani ◽  
Khalid Jadoon
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Mineral Density ◽  
Neck Of Femur ◽  
Vitamin D Levels ◽  
Significant Difference

Abstract Background/Aims  Vitamin D deficiency is associated with more severe presentation of primary hyperparathyroidism (PTHP) with high parathyroid hormone (PTH) levels and reduced bone mineral density (BMD). We analyzed data to determine if vitamin D levels had any impact on PTH, serum calcium and BMD at diagnosis and 3 years, in patients being managed conservatively. Methods  Retrospective analysis of patients presenting with PHPT. Based on vitamin D level at diagnosis, patients were divided into two groups; vitamin D sufficient (≥ 50 nmol/L) and vitamin D insufficient (≤ 50 nmol/L). The two groups were compared for age, serum calcium and PTH levels at diagnosis and after mean follow up of 3 years. BMD at forearm and neck of femur (NOF) was only analyzed in the two groups at diagnosis, due to lack of 3 year’s data. Results  There were a total of 93 patients, 17 males, mean age 70; range 38-90. Mean vitamin D level was 73.39 nmol/L in sufficient group (n = 42) and 34.48 nmol/L in insufficient group (n = 40), (difference between means -38.91, 95% confidence interval -45.49 to -32.33, p &lt; 0.0001). There was no significant difference in age, serum calcium and PTH at the time of diagnosis. After three years, there was no significant difference in vitamin D levels between the two groups (mean vitamin D 72.17 nmol/L in sufficient group and 61.48 nmol/L in insufficient group). Despite rise in vitamin D level in insufficient group, no significant change was observed in this group in PTH and serum calcium levels. BMD was lower at both sites in vitamin D sufficient group and difference was statistically significant at NOF. Data were analyzed using unpaired t test and presented as mean ± SEM. Conclusion  50% of patients presenting with PHPT were vitamin D insufficient at diagnosis. Vitamin D was adequately replaced so that at 3 years there was no significant difference in vitamin D status in the two groups. Serum calcium and PTH were no different in the two groups at diagnosis and at three years, despite rise in vitamin D levels in the insufficient group. Interestingly, BMD was lower at forearm and neck of femur in those with sufficient vitamin D levels and the difference was statistically significant at neck of femur. Our data show that vitamin D insufficiency does not have any significant impact on PTH and calcium levels and that vitamin D replacement is safe in PHPT and does not impact serum calcium and PTH levels in the short term. Lower BMD in those with adequate vitamin D levels is difficult to explain and needs further research. Disclosure  M. Khalid: None. V. Deshani: None. K. Jadoon: None.

scholarly journals Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Combination Treatment ◽  
Mass Gain ◽  
Ovariectomized Rats ◽  
Concomitant Treatment ◽  
Mineral Density ◽  
Ovx Rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.

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.

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