scholarly journals Negligible Effect of Estrogen Deficiency on Development of Skeletal Changes Induced by Type 1 Diabetes in Experimental Rat Models

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Aleksandra Janas ◽  
Ewa Kruczek ◽  
Piotr Londzin ◽  
Sławomir Borymski ◽  
Zenon P. Czuba ◽  
...  

Although postmenopausal osteoporosis often occurs concurrently with diabetes, little is known about interactions between estrogen deficiency and hyperglycemia in the skeletal system. In the present study, the effects of estrogen deficiency on the development of biochemical, microstructural, and mechanical changes induced by streptozotocin-induced diabetes mellitus (DM) in the rat skeletal system were investigated. The experiments were carried out on nonovariectomized (NOVX) and ovariectomized (OVX) control and diabetic mature female Wistar rats. Serum levels of bone turnover markers (CTX-I and osteocalcin) and 23 cytokines, bone mass and mineralization, histomorphometric parameters, and mechanical properties of cancellous and compact bone were determined. The results were subjected to two-way ANOVA and principal component analysis (PCA). Estrogen deficiency induced osteoporotic changes, with increased bone resorption and formation, and worsening of microstructure (femoral metaphyseal BV/TV decreased by 13.0%) and mechanical properties of cancellous bone (the maximum load in the proximal tibial metaphysis decreased by 34.2%). DM in both the NOVX and OVX rats decreased bone mass, increased bone resorption and decreased bone formation, and worsened cancellous bone microarchitecture (for example, the femoral metaphyseal BV/TV decreased by 17.3% and 18.1%, respectively, in relation to the NOVX controls) and strength (the maximum load in the proximal tibial metaphysis decreased by 35.4% and 48.1%, respectively, in relation to the NOVX controls). Only in the diabetic rats, profound increases in some cytokine levels were noted. In conclusion, the changes induced by DM in female rats were only slightly intensified by estrogen deficiency. Despite similar effects on bone microstructure and strength, the influence of DM on the skeletal system was based on more profound systemic homeostasis changes than those induced by estrogen deficiency.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Urszula Cegieła ◽  
Joanna Folwarczna ◽  
Maria Pytlik ◽  
Grażyna Zgórka

Some plant species belonging toTrifoliumL. genus are a source of isoflavones considered to exert phytoestrogenic activities. The aim of the present study was to examine the effects of standardized extract obtained from aerial parts ofTrifolium mediumL., in comparison with the extract ofTrifolium pratenseL., on the development of estrogen deficiency-induced osteoporosis in rats. BothTrifoliumextracts, at doses corresponding to 10 and 20 mg/kg of isoflavone aglycones daily, or estradiol (0.2 mg/kg daily), were administered orally to ovariectomized (OVX) rats for 4 weeks. Serum bone turnover markers, bone mass, mineralization, and mechanical properties were studied. In OVX control rats, mechanical properties of the tibial metaphysis and femoral neck were strongly worsened in comparison with sham-operated control rats, and those of femoral diaphysis were unaffected. Estradiol counteracted the worsening of the tibial strength and increases in bone turnover markers. Both extracts significantly increased the strength of the femoral diaphysis and calcium and phosphorus content in the bone mineral, but onlyT. pratenseextract increased the strength of the tibial metaphysis. In conclusion, effects of bothTrifoliumextracts differed from those of estradiol. It is possible that other than isoflavone extract constituents contributed to their skeletal effects.


2016 ◽  
Vol 63 (2) ◽  
Author(s):  
Joanna Folwarczna ◽  
Maria Zych ◽  
Barbara Nowińska ◽  
Maria Pytlik ◽  
Magdalena Bialik ◽  
...  

Diosgenin is a steroidal sapogenin present in fenugreek and Dioscorea spp. as glycosides (saponins). Diosgenin has already been reported to inhibit osteoclastogenesis and to stimulate osteogenic activity of osteoblastic cells in vitro, and to exert some antiosteoporotic effects in rats in vivo. The aim of the present study was to investigate the effects of diosgenin administration on the skeletal system of rats with normal estrogen level and with estrogen deficiency induced by bilateral ovariectomy. The experiments were carried out on 3-month-old non-ovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving diosgenin (50 mg/kg p.o. daily) for 4 weeks. Serum bone turnover markers, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diosgenin improved some investigated parameters in both non-ovariectomized and ovariectomized rats, in which estrogen deficiency induced osteoporotic changes. Diosgenin increased compact bone formation and probably inhibited cancellous bone resorption, which led to improvement of mechanical properties of compact and cancellous bone. In conclusion, this in vivo study demonstrated that diosgenin may be one of sparse compounds increasing bone formation.


1998 ◽  
Vol 274 (2) ◽  
pp. E328-E335 ◽  
Author(s):  
C. K. Lea ◽  
A. M. Flanagan

The effect of androstenedione (ADIONE) slow-release pellets on cancellous bone volume (BV/TV) at the tibial metaphysis was investigated in ovariectomized (OVX) rats at various times from 21 to 180 days. Plasma levels of ADIONE and testosterone (T) in OVX rats were significantly reduced at 21 days and were restored close to levels in the sham rats with the 1.5-mg ADIONE pellet. OVX animals with and without ADIONE pellets resulted in close to a 50% reduction in BV/TV by day 21. By day 180, OVX rats had only ∼5% BV/TV, whereas that in ADIONE-treated OVX rats was significantly greater at ∼12%. The reduced BV/TV was associated with increased bone resorption and formation. In a separate 90-day experiment, we found that the antiandrogen, Casodex, abrogated the ADIONE-induced skeletal-protective effect in OVX rats, whereas the antiaromatase, Arimidex, had no effect. This provides evidence that ADIONE protects against the development of osteopenia in the estrogen-deficient rat and mediates its effect through androgens and not estrogens.


2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  

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.


Folia Medica ◽  
2017 ◽  
Vol 59 (2) ◽  
pp. 139-158 ◽  
Author(s):  
Julia Fedotova ◽  
Daria Zarembo ◽  
Jozef Dragasek ◽  
Martin Caprnda ◽  
Peter Kruzliak ◽  
...  

AbstractBackground:Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance.Materials and methods:The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT).Results:Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats.Conclusion:Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ilona Kaczmarczyk-Sedlak ◽  
Weronika Wojnar ◽  
Maria Zych ◽  
Ewa Ozimina-Kamińska ◽  
Joanna Taranowicz ◽  
...  

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance areAstragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra,andPueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17β-estradiol, it can mimic estradiol’s effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.


2003 ◽  
Vol 95 (3) ◽  
pp. 1032-1037 ◽  
Author(s):  
Akiko Honda ◽  
Naota Sogo ◽  
Seigo Nagasawa ◽  
Takuya Shimizu ◽  
Yoshihisa Umemura

The effect of jump exercise on middle-aged osteopenic rats was investigated. Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. After the experiment, the right tibia and femur were dissected, and blood was obtained from each rat. OVX rats were observed to have increased body weights and decreased bone mass in their tibiae and femurs. Jump-exercised rats, on the other hand, had significantly increased tibial bone mass, strength, and cortical areas. The bone mass and strength of OVX exercised rats increased to approximately the same extent as Sham exercised rats, despite estrogen deficiency or osteopenia. Our data suggest that jump exercise has beneficial effects on lower limb bone mass, strength, bone mineral density, and morphometry in middle-aged osteopenic rats, as well as in Sham rats.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lu-lin Liu ◽  
Gong-wen Liu ◽  
Hui Liu ◽  
Kai Zhao ◽  
You-jia Xu

Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.


2021 ◽  
pp. 1-22
Author(s):  
Jonathan M. Scott ◽  
Elizabeth A. Swallow ◽  
Corinne E. Metzger ◽  
Rachel Kohler ◽  
Joseph M. Wallace ◽  
...  

Abstract In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.


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