scholarly journals Metabolomics and physiological analysis of the effect of calcium supplements on reducing bone loss in ovariectomized rats by increasing estradiol levels

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hongmei Mao ◽  
Wenjun Wang ◽  
Lili Shi ◽  
Chen Chen ◽  
Chao Han ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Calcium Supplementation ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Type I ◽  
Serum Estradiol ◽  
Mineral Density ◽  
Estradiol Levels

Abstract Background Data from the 2010–2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen. Objective This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats. Methods Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO3 (OVX-LC-H). CaCO3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed. Results The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO3 supplementation (p < 0.01). The administration of 2800 mg/kg CaCO3 decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced. Conclusions The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

scholarly journals Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats

2001 ◽  
Vol 86 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Joseé Gala ◽  
Manuel Di´az-curiel ◽  
Concepcioó de la Piedra ◽  
Jesu´s Calero
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Exercise Programme ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Standard Diet ◽  
Mineral Density ◽  
Left Femur ◽  
Ovx Rats

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Female Rats ◽  
Wild Type ◽  
Mineral Density ◽  
Transgenic Rats ◽  
Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

scholarly journals Relationship between Bone Mineral Density and Maturity Index in Cervical Smears, Serum Estradiol Levels and Body Mass Index

2013 ◽  
Vol 5 (6) ◽  
Author(s):  
Homayoun Sheikholeslami ◽  
Majid Sotodeh ◽  
Amir Javadi ◽  
Neda Nasirian ◽  
Amir Mohammad Kazemifar ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Mass Index ◽  
Body Mass ◽  
Bone Mineral ◽  
Maturity Index ◽  
Serum Estradiol ◽  
Mineral Density ◽  
Cervical Smears ◽  
Estradiol Levels

scholarly journals Recovery Effects of a 180 mT Static Magnetic Field on Bone Mineral Density of Osteoporotic Lumbar Vertebrae in Ovariectomized Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Shenzhi Xu ◽  
Hideyuki Okano ◽  
Naohide Tomita ◽  
Yoshito Ikada
Keyword(s):  
Magnetic Field ◽  
Bone Mineral Density ◽  
Bone Mineral ◽  
Static Magnetic Field ◽  
Lumbar Vertebrae ◽  
Exposed Group ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Moderate Intensity ◽  
Mineral Density

The effects of a moderate-intensity static magnetic field (SMF) on osteoporosis of the lumbar vertebrae were studied in ovariectomized rats. A small disc magnet (maximum magnetic flux density 180 mT) was implanted to the right side of spinous process of the third lumbar vertebra. Female rats in the growth stage (10 weeks old) were randomly divided into 4 groups: (i) ovariectomized and implanted with a disc magnet (SMF); (ii) ovariectomized and implanted with a nonmagnetized disc (sham); (iii) ovariectomized alone (OVX) and (vi) intact, nonoperated cage control (CTL). The blood serum 17--estradiol (E2) concentrations were measured by radioimmunoassay, and the bone mineral density (BMD) values of the femurs and the lumbar vertebrae were assessed by dual energy X-ray absorptiometry. The E2concentrations were statistically significantly lower for all three operated groups than those of the CTL group at the 6th week. Although there was no statistical significant difference in the E2concentrations between the SMF-exposed and sham-exposed groups, the BMD values of the lumbar vertebrae proximal to the SMF-exposed area statistically significantly increased in the SMF-exposed group than in the sham-exposed group. These results suggest that the SMF increased the BMD values of osteoporotic lumbar vertebrae in the ovariectomized rats.

scholarly journals Plasma nitrate+nitrite levels are regulated by ovarian steroids but do not correlate with trabecular bone mineral density in rats

1998 ◽  
Vol 159 (1) ◽  
pp. 27-34 ◽  
Author(s):  
RL van Bezooijen ◽  
I Que ◽  
AG Ederveen ◽  
HJ Kloosterboer ◽  
SE Papapoulos ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Ovariectomized Rats ◽  
No Production ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Oestrogen Treatment ◽  
Plasma Nitrate

Nitric oxide (NO) is a mediator of bone metabolism and its production is under the control of gender hormones in several cell types or tissues. Changes in endogenous NO production, measured as plasma nitrate+nitrite levels, may therefore contribute to ovariectomy (OVX)-induced bone loss. We studied plasma nitrate+nitrite levels and trabecular bone mineral density (TBMD) 4 weeks after sham-operation or OVX in rats receiving various hormonal treatments. OVX decreased plasma nitrate+nitrite levels significantly and this was accompanied by a significant decrease in TBMD. Treatment with oral ethinyl oestradiol (EE) and subcutaneous 17beta-oestradiol dose-dependently prevented the decrease in plasma nitrate+nitrite levels after OVX, but treatment with oral 17beta-oestradiol did not. Oestrogen treatment, 17beta-oestradiol (s. c. or orally) or EE (orally), prevented the OVX-induced decrease in TBMD. Treatment of sham-operated rats with the anti-oestrogen ICI164, 384 induced a significant decrease in TBMD that corresponded to 54% of the decrease observed after OVX, but did not affect plasma nitrate+nitrite levels. Treatment of ovariectomized rats with Org 2058, a pure progestagen, did not prevent bone loss, but prevented the decrease in plasma nitrate+nitrite levels dose-dependently. Treatment with tibolone, a synthetic steroid with combined weak oestrogenic, progestagenic, and androgenic properties, or with progestagen in combination with EE completely prevented bone loss after OVX. These treatments, however, only partly prevented the OVX-induced decrease in plasma nitrate+nitrite levels. In conclusion, OVX decreased both TBMD and plasma nitrate+nitrite levels. Although plasma nitrate+nitrite levels were under the control of both oestrogen and progesterone, TBMD was affected by oestrogen only. Decreased systemic production of NO is, therefore, not involved in OVX-induced bone loss in rats.

scholarly journals Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

2019 ◽  
Vol 39 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Katalin Gulyás ◽  
Ágnes Horváth ◽  
Edit Végh ◽  
Anita Pusztai ◽  
Ágnes Szentpétery ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Mineral ◽  
Certolizumab Pegol ◽  
Joint Destruction ◽  
Type I ◽  
Mineral Density ◽  
Tnf Α

Abstract Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.

scholarly journals Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

2016 ◽  
Vol 38 (1) ◽  
pp. 283-294 ◽  
Author(s):  
Zhanhai Yin ◽  
Yan Zhang ◽  
Zheyang Wang ◽  
Lin Ding ◽  
Ainiwaerjiang Damaolar ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Femoral Neck ◽  
Bone Mineral ◽  
Neck Region ◽  
Ovariectomized Rats ◽  
Type I ◽  
Mrna Levels ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Ovx Rats

Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

scholarly journals Relationship of Serum Sex Steroid Levels and Bone Turnover Markers with Bone Mineral Density in Men and Women: A Key Role for Bioavailable Estrogen1

1998 ◽  
Vol 83 (7) ◽  
pp. 2266-2274 ◽  
Author(s):  
Sundeep Khosla ◽  
L. Joseph Melton ◽  
Elizabeth J. Atkinson ◽  
W. M. O’Fallon ◽  
George G. Klee ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Life Span ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Resorption Marker ◽  
Type I ◽  
Mineral Density ◽  
Men And Women ◽  
Aging Men

Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally with age in men. Thus, it has been difficult to attribute bone loss in aging men to either T or E deficiency. Here, we show in a population-based, age-stratified sample of 346 men, aged 23–90 yr, that serum total T and E (estradiol plus estrone) levels decreased over the life span by 30% and 12%, respectively, but bioavailable (or nonsex hormone-binding globulin-bound) T and E levels decreased by 64% and 47%, respectively. In these men and in a parallel cohort of 304 women, aged 21–94 yr, serum PTH increased 84% and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx) excretion, a bone resorption marker, increased 77% and 80% between age 50–85 yr in the men and women, respectively. By univariate analyses, serum bioavailable T and E levels correlated positively with bone mineral density (BMD) at the total body, spine, proximal femur, and distal radius and negatively with urinary NTx excretion in men and women. Urinary NTx excretion was also negatively associated with BMD in both sexes. By multivariate analyses, however, serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women. Thus, bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women. These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E deficiency not just in postmenopausal women, but also in men.

scholarly journals Effect of calcium supplementation combined with fucoidan and chitooligisaccaride on bone mineral density in ovariectomized rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Mi‐Hyun Kim ◽  
Sunju Yun ◽  
Myung‐Hwa Kang ◽  
Mi‐Kyeong Choi ◽  
Jung Dae Lee ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Calcium Supplementation ◽  
Ovariectomized Rats ◽  
Mineral Density
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