scholarly journals Effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized rats

2021 ◽  
Vol 18 (6) ◽  
pp. 1285-1289
Author(s):  
Fang Yu ◽  
QingNa Lv ◽  
ZhiHong Tong ◽  
WenJi Song ◽  
ZhengNan Zhao ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mrna Expression ◽  
Potential Effect ◽  
Bone Morphogenetic Protein 2 ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Total Flavonoids ◽  
Rat Serum ◽  
Ovx Rats ◽  
Biochemical Indices

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from rat serum and bone. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis, namely, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats through the WNT signaling and BMP-2 signaling pathways.

scholarly journals Effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized rats

2021 ◽  
Vol 18 (7) ◽  
pp. 1513-1517
Author(s):  
ZhengNan Zhao ◽  
XiangLong Yang ◽  
Fang Yu ◽  
WenJi Song ◽  
HaiDong Liang
Keyword(s):  
Bone Loss ◽  
Mrna Expression ◽  
Potential Effect ◽  
Bone Morphogenetic Protein 2 ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Total Flavonoids ◽  
Ovx Rats ◽  
Post Operation ◽  
Biochemical Indices

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from the serum and bone of the rats. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis: alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats via WNT signaling and BMP-2 signaling pathways.

scholarly journals The Preventive Effect of Biochanin A on Bone Loss in Ovariectomized Rats: Involvement in Regulation of Growth and Activity of Osteoblasts and Osteoclasts

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shu-Jem Su ◽  
Yao-Tsung Yeh ◽  
Huey-Wen Shyu
Keyword(s):  
Bone Loss ◽  
Mrna Expression ◽  
Biological Effects ◽  
Biochanin A ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Ovx Rats

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX ratsin vivoand on the development of osteoblasts and osteoclastsin vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factorα(TNF-α) and interleukin-1β(IL-1β).In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.

Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels in ovariectomized rats

2009 ◽  
Vol 87 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Yong-Qi Li ◽  
Hui Ji ◽  
Yang Shen ◽  
Li-Ju Ding ◽  
Pei Zhuang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
Chronic Treatment ◽  
Transforming Growth Factor ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Receptor Antagonists ◽  
Ovx Rats ◽  
At1 Receptor Antagonists

Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-β1 (TGF-β1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1–L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-β1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-β1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels and did not accelerate ovariectomy-induced bone loss in rats.

scholarly journals The miR-1906 mimic attenuates bone loss in osteoporosis by down-regulating the TLR4/MyD88/NF‐κB pathway

2021 ◽  
Vol 107 (4) ◽  
pp. 469-478
Author(s):  
H. Xie ◽  
L. Cao ◽  
L. Ye ◽  
G. Shan ◽  
W. Song
Keyword(s):  
Bone Loss ◽  
Cell Viability ◽  
Mrna Expression ◽  
Biochemical Parameters ◽  
Lumbar Vertebrae ◽  
Whole Body ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Cellular Toxicity ◽  
Ovx Rats

AbstractIn this study, the ability of microRNA-1906 (miR-1906) to attenuate bone loss in osteoporosis was evaluated by measuring the effects of a miR-1906 mimic and inhibitor on the cellular toxicity and cell viability of MC3T3‐E1 cells. Bone marrow-derived macrophage (BMM) cells were isolated from female mice, and tartrate-resistant acid phosphatase signalling was performed in miR-1906 mimic-treated, receptor-activated nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced osteoclasts. In-vivo, osteoporosis was induced by ovariectomy (OVX). Rats were treated with 500 nmol/kg of the miR-1906 mimic via intrathecal administration for 10 consecutive days following surgery. The effect of the miR-1906 mimic on bone mineral density (BMD) in OVX rats was observed in the whole body, lumbar vertebrae and femur. Levels of biochemical parameters and cytokines in the serum of miR-1906 mimic-treated OVX rats were analysed. The mRNA expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-38 and NF-κB in tibias of osteoporotic rats (induced by ovariectomy) was observed using quantitative reverse-transcription polymerase chain reaction. Treatment with the miR-1906 mimic reduced cellular toxicity and enhanced the cell viability of MC3T3‐E1 cells. Furthermore, osteoclastogenesis in miR-1906 mimic-treated, RANKL-induced osteoclast cells was reduced, whereas the BMD in the miR-1906 mimic-treated group was higher than in the OVX group of rats. Treatment with the miR-1906 mimic also increased levels of biochemical parameters and cytokines in the serum of ovariectomised rats. Finally, mRNA expression levels of TLR4, MyD88, p-38 and NF-κB were lower in the tibias of miR-1906 mimic-treated rats than in those of OVX rats. In conclusion, the miR-1906 mimic reduces bone loss in rats with ovariectomy-induced osteoporosis by regulating the TLR4/MyD88/NF‐κB pathway.

scholarly journals Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/β-catenin pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yimei Hu ◽  
Panyun Mu ◽  
Xu Ma ◽  
Jingru Shi ◽  
Zhendong Zhong ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Bone Loss ◽  
Bone Formation ◽  
Chinese Herb ◽  
Estrogen Deficiency ◽  
Ovariectomized Rats ◽  
Cartilage Tissue ◽  
Total Flavonoids ◽  
Ovx Rats ◽  
Rhizoma Drynariae

Abstract Background Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether the Rhizoma drynariae total flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss. Methods Three-month-old Sprague–Dawley rats were ovariectomized (OVX) and then treated with CaCO3, RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, β-catenin, and phosphorylated β-catenin (p-β-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0 Results RDTF combined with CaCO3 could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3 also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3 supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, β-catenin and p-β-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3 could activate the Wnt3a/β-catenin pathway. Conclusions RDTF combined with CaCO3 could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

scholarly journals Effects of Kalsis, A Dietary Supplement, on Bone Metabolism in the Ovariectomized Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mercedes Montero ◽  
Manuel Díaz-Curiel ◽  
David Guede ◽  
Jose Ramón Caeiro ◽  
Marta Martín-Fernández ◽  
...  
Keyword(s):  
Bone Loss ◽  
Group Treatment ◽  
Food Supplement ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Ovx Rats ◽  
Carboxyterminal Telopeptide ◽  
Trabecular Number

We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (n=12): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (μCT) in femur and serum osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP),β-isomer of carboxyterminal telopeptide of collagen I (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase (TRAP) were performed. Treatment with Kalsis prevented BMD loss in OVX group.μCT showed a decrease in BV/TV, and trabecular number, and an increase in trabecular separation in OVX rats. Kalsis administration attenuated partially bone loss observed byμCT due to ovariectomy. BGP, PINP, and the resorption index (CTX/TRAP) were increased in OVX group. Treatment with Kalsis maintained this increase. The mechanism of action of this supplement is not through a decrease in bone remodelling rate. The antioxidant action of this food supplement, due to the synergism of all its components, as a cause of its beneficial effect is suggested.

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.

scholarly journals Effects of the Peroxisome Proliferator-Activated Receptor (PPAR)-δ Agonist GW501516 on Bone and Muscle in Ovariectomized Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2178-2189 ◽  
Author(s):  
M. P. Mosti ◽  
A. K. Stunes ◽  
M. Ericsson ◽  
H. Pullisaar ◽  
J. E. Reseland ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Loss ◽  
Ovariectomized Rats ◽  
Whole Body ◽  
Control Group ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Mineral Density ◽  
Muscle Morphology ◽  
Ovx Rats

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

scholarly journals Shockwave Therapy Modulates the Expression of BMP2 for Prevention of Bone and Cartilage Loss in the Lower Limbs of Postmenopausal Osteoporosis Rat Model

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 614
Author(s):  
Shan-Ling Hsu ◽  
Wen-Yi Chou ◽  
Chieh-Cheng Hsu ◽  
Jih-Yang Ko ◽  
Shun-Wun Jhan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cyclin D1 ◽  
Family Member ◽  
Peak Load ◽  
Lower Limbs ◽  
Bone Morphogenetic Protein 2 ◽  
Cartilage Loss ◽  
Protective Effects ◽  
Shockwave Therapy ◽  
Ovx Rats

Osteoporosis (OP) causes bone loss and weakness, increasing the risk of bone fracture. In this study, rats were divided into Sham, OP, SW(F) (0.25 mJ/mm2 with 1600 impulses to the left medial femur), and SW(T) (0.25 mJ/mm2 with 1600 impulses to the left medial tibia). The bone strength results following SW(T) were better than SW(F) in the modulus, extension at peak load, handleability, and strain at break. SW(T) had the best prevention for bone loss in both lower limbs of ovariectomized (OVX) rats. The cartilage cellular matrixes of both knees were improved in SW(T) and SW(F) compared to that of OP. Serum bone morphogenetic protein 2 (BMP2) in rats undergoing SW(T) or SW(F) was significantly improved compared to that in Sham and OP. The expressions of BMP2, BMP4, and SMAD family member 4 (Smad4) in addition to the Wnt family member 3A (Wnt3a) and Cyclin D1 signaling key factors were significantly induced in the cartilage of both knees by shockwave (SW). SW(T) presented the best efficacy to induce serum BMP2 to prevent bone loss from both lower limbs. Here, we display the protective effects of SW therapy to induce BMP2, BMP4, Smad4, Wnt3a, and Cyclin D1 signaling factors for cartilage loss in both knees of OVX rats.

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.

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