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Weight-bearing training, as one of resistance exercises, is beneficial to bone health. Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. Animals lacking MSTN show increased bone mineral density (BMD). The aim of this study was to investigate the preventive effect of weight-bearing training on bone loss in ovariectomized rats and whether it was related to MSTN. In this study, the rats were randomly assigned to three group: Sham-ovariectomized (Sham), ovariectomized (OVX), ovariectomized and weight-bearing training (OWT). The rats in the OWT group ran at 20-m/min bearing with 35% of their body weight for 6 days/week. After 10 weeks, compared with the OVX group, weight-bearing training increased the BMD of total femur and trabecular bone by 8.13% and 57.44%, respectively. The OVX-induced destruction of bone microarchitecture including the thickness and number of trabeculae and bone volume fraction was all significantly improved (9.26%, 47.68%, 63.03%) in the OWT group. The OVX-induced degradation of bone mechanical properties was significantly enhanced in the OWT group (maximum load increased by 35.46%, stiffness increased by 89.19%, energy absorption increased by 53.4%; elastic modulus increased by 26.3%). Ten-week weight-bearing training also significantly upregulated the mRNA and protein expression of Wnt1 and β-catenin, which is crucial in bone development. Compared with the Sham group, MSTN in serum and muscle increased in the OVX group, but it decreased in the OWT group compared with the OVX group. Its receptor ActRIIB and downstream molecules Smad2/3 in the OVX group were downregulated in bone by weight-bearing training. The results indicated that MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats., (© 2021. University of Navarra.)

Objective: To study the curative effect of bionic tiger-bone powder on osteoporosis in ovariectomized rats and investigate its mechanism., Methods: Overall, a 120 female Wistar rats were randomly divided into Sham (sham-operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger-bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger-bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L 6 vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three-point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson's trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting., Results: Compared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P < 0.05), while the CTX level was lower (P < 0.05). Bone collagen fiber structures in the TB and TB + VD groups were repaired, and the collagen content was significantly higher than that in the OVX group (P < 0.05). In the TB group, BMP-2, P-SMAD1/5, RUNX2 and OPG levels were increased in bone tissue (P < 0.01), RANKL levels were decreased (P < 0.01), and the bone microstructure and biomechanical strength were improved., Conclusion: Bionic tiger-bone powder promotes osteogenesis by activating the BMP2/SMAD/RUNX2 signaling pathway, suppresses osteoclasts by downregulating the OPG/RANK/RANKL signaling pathway, increases bone collagen content, and improves bone microstructure and bone biomechanical strength., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To explore the effect of physical exercise (EXE), strontium ranelate (SR), or their combination on bone status in ovariectomized (OVX) rats., Design: Sixty female Wistar rats were randomized to one of five groups: sham (Sh), OVX (O), OVX+EXE (OE), OVX+SR (OSR), and OVX+EXE+SR (OESR). Animals in EXE groups were subjected to 10 drops per day (45 cm in height); rats in SR groups received 625 mg/kg/day of SR, 5 days/week for 8 weeks. Bone mineral density (BMD) and bone mineral content (BMC, dual-energy X-ray absorptiometry (DXA)), mechanical strength of the left femur (three-point bending test), and femur microarchitecture of (micro-computed tomography imaging, microCT) analyses were performed to characterize biomechanical and trabecular/cortical structure. Bone remodeling, osteocyte apoptosis, and lipid content were evaluated by ELISA and immunofluorescence tests., Results: In OVX rats, whole-body BMD, trabecular parameters, and osteocalcin (OCN) levels decreased, while weight, lean/fat mass, osteocyte apoptosis, and lipid content all increased. EXE after ovariectomy improved BMD and BMC, trabecular parameters, cross-sectional area (CSA), moment of inertia, and OCN levels while decreasing osteocyte apoptosis and lipid content. SR treatment increased BMD and BMC, trabecular parameters, CSA, stiffness, OCN, and alkaline phosphatase (ALP) levels. Furthermore, fat mass, N-telopeptide (NTX) level, osteocyte apoptosis, and lipid content significantly decreased. The combination of both EXE and SR improved bone parameters compared with EXE or SR alone., Conclusion: EXE and SR had positive and synergistic effects on bone formation and resorption.

Introduction: Intermittent 1-34 parathyroid hormone (iPTH) administration, a bone-forming treatment, is widely used as a therapy for severe osteoporosis. It can only be used for a maximum of 24 mo and must be followed by an antiresorptive drug to retain the new formed tissue. Mechanical load, in the form of low-intensity and high-frequency vibration, has received considerable attention due to its ability to prevent bone loss., Aim: To investigate the ability of whole body mechanical vibration (MV) to potentiate the anabolic effects of iPTH and to inhibit bone resorption following discontinuation of iPTH treatment in estrogen-deficient rats., Methodology: Fifty-four 6-month-old female Wistar rats were ovariectomized (OVX) or sham-operated. After 5 mo, they were divided into 7 groups: Sham - non-OVX; Control - OVX, vehicle for 60 d; MV - OVX, submitted to MV for 60 d; PTH60d - OVX, injected with iPTH for 60 d; PTH+MV - OVX, injected with iPTH combined with MV for 60 d; PTH30d - OVX, injected with iPTH for 30 d, and untreated for 30 d; PTH30d/MV30d - OVX, injected with iPTH for 30 d, followed by MV for 30 d. Bone mineral density (BMD) and body composition (lean mass and fat) were evaluated at OVX (T0), the beginning (T1), and at the end (T2) of treatments by dual X-ray absorptiometry (DXA). Femurs were processed for histomorphometry (bone volume - BV/TV and cortical thickness - Ct.Th) and tibias for biomechanical test., Results: Body composition and BMD were similar among the groups at T0. In T2, MV presented higher fat than other groups (except PTH60d) and PTH30d/MV30d showed greater lean mass than Control. At T1, Sham presented the highest BMD, but between T1 vs T2 there was an increase in all iPTH-treated groups. At T2, BMD was higher in PTH60d and PTH+MV than in the Control and MV groups. The highest BV/TV was observed in the PTH+MV group, followed by PTH60d. Cortical thickness was increased in PTH60d and PTH+MV compared to Sham. Vibration applied post-iPTH (PTH30d/MV30d) improved the force at failure in tibias when compared to Sham and Control groups., Conclusion: MV potentiated iPTH anabolic effects in cancellous bone; however, MV was unable to maintain bone mass after stopping iPTH in ovariectomized rats., (Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of marine fish collagen oligopeptide and calcium aspartate alone or in combination on bone mineral density in ovariectomized rats., Methods: Sixty three-month-old SPF Wistar female rats were randomly divided into 6 groups according to their body weight: sham operation group, model control group(ovariectomy), calcium aspartate group(ovariectomy), marine fish collagen oligopeptide group(ovariectomy), aspartate calcium + marine fish collagen oligopeptide group(ovariectomy) and calcium carbonate control group(ovariectomy), 10 rats in each group. The sham operation group and the model control group were given the same volume of pure water by gavage, and the other groups were intragastrically administered with calcium aspartate(116. 7 mg/kg), marine fish collagen oligopeptide(250 mg/kg), calcium aspartate(116. 7 mg/kg) + marine fish collagen oligopeptide(250 mg/kg), calcium carbonate(35. 6 mg/kg), and the test substance was continuously administered for 90 days. After 90 days, the animals were sacrificed, and the liver and kidney of the rats were taken to calculate the organ coefficient and pathological examination. The rat femurs were taken to measure bone mineral density and bone calcium content and rat serum was used to determine serum calcium, phosphorus concentration and alkaline phosphatase(ALP) activity., Results: Bone mineral density and bone calcium content in the model group were significantly lower than those in the sham operation group(P<0. 05), indicating that the osteoporosis model was successfully established by oophorectomy. There was no significant difference in the organ index of each group(P>0. 05), liver/kidney HE staining microscopic examination showed no abnormal changes, indicating the safety of the test substances. The bone mineral density of the aspartate calcium + marine fish collagen oligopeptide group was significantly greater than that of the model group(P<0. 05). The bone mineral density of the aspartate calcium group and the marine fish collagen oligopeptide group was larger than that of the model group, but there was no significant difference(P>0. 05). Compared with that in the model group, the calcium content of calcium aspartate + marine fish collagen oligopeptide group was significantly higher(P<0. 05). Compared with that in the calcium aspartate group, the calcium content of calcium aspartate + marine fish collagen oligopeptide group was higher(P<0. 05), there was no significant difference in serum calcium concentration between groups(P>0. 05). Compared with that in the model group, serum phosphorus concentration in the aspartate calcium group, marine fish collagen oligopeptide group, aspartate calcium + marine fish collagen oligopeptide group was significantly higher(P<0. 05) and ALP activity was significantly reduced(P<0. 05)., Conclusion: The combination of calcium aspartate and marine fish collagen oligopeptide has a significant effect on increasing bone mineral density, also indicating that marine fish bone collagen oligopeptide could promote absorption of calcium aspartate.

Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3β (GSK3β) to GSK3β and increased ratio of p-β-catenin to β-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/β-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs., (© 2018 John Wiley & Sons, Ltd.)

To investigate the effect of Xianling Gubao capsule in preventing postmenopausal osteoporosis, forty-eight female Wistar rats were randomly divided into four groups: sham group (Sham), ovariectomized group (OVX), ethinylestradiol group (EE) and Xianling Gubao capsule group (XLGB). Rats in each group received ovariectomy, except for sham group. The XLGB group received Xianling Gubao capsule at the dose of 378 mg·kg⁻¹·d⁻¹. The dosage of EE group was 200 μg·kg⁻¹·d⁻¹, and OVX and Sham groups were only fed with equal volume of distilled water. All of the rats were put to death two months later. Bone mineral density, bone biomechanics, bone histomorphometry Micro-CT scanning and organ index of vital organs were calculated and pathologically observed. There was no significant difference in the body weight of rats and organ indexes of lung, kidney, heart and spleen in the experimental groups. There was also no significant change in their pathological observation, but the uterine index of OVX group and XLGB group was significantly lower than that of Sham group. According to the results of BMD test, compared with the OVX group, femurs and vertebrae BMD of the other three groups were increased, with statistically significant differences. On the basis of the results of bone biomechanical test, compared with OVX group, the maximum load values of femur and vertebrae of the other three groups were increased, with statistically significant differences, while the change of elastic modulus was not statistically significant. According to the bone histomorphometry results of VG staining, compared with Sham group, the number of trabecular bone was significantly lower than that in OVX group. Compared with OVX group, the number of trabecular bone in EE group and XLGB group was increased, but with no significant difference between EE and XLGB groups. The results of serum biochemical indexes showed that compared with Sham group, osteocalcin (OC) decreased, while tartrate resistant acid phosphatase 5b (TRACP 5b) increased in OVX group, with statistically significant differences. Compared with OVX group, the OC content of XLGB group and EE group increased, while the content of TRACP 5b decreased, with statistically significant differences. On the basis of the results of Micro-CT scanning, the change trends of femur volume BMD, number of trabecular bone (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone separation (Tb.Sp), bone volume/tissue volume (BV/TV) in the groups were consistent with those of bone histomorphometry. There was no significant change in femoral cortical bone between the two groups. Xianling Gubao capsule can prevent osteoporosis in ovariectomized rats. The possible mechanism is the dual activity of inhibiting bone resorption and improving bone formation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Context Eucommiae Cortex and Radix Dipsaci, occurring in a ratio of 1:1 in Du-Zhong-Wan (DZW), a Chinese herbal medicine, is available as a water extract followed by ethanol precipitation for the treatment of osteoporosis, fractures and menopausal syndrome. Objective This study investigates the protective effects of DZW in ovariectomy (OVX)-induced bone loss in a rat osteopenia model. Materials and methods Sixty Sprague-Dawley rats were randomly divided into the sham-operated group (SHAM) and five OVX subgroups: OVX with vehicle (OVX), 17β-estradiol (E2) and with three graded doses of DZW. Daily oral administration of the different samples started on the fifth week and lasted for 12 weeks, respectively. The body weight, uterus wet weight, serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and immunohistochemistry were examined. Results Compared with the SHAM group, the DZW treatment significantly reversed the osteoporotic changes in OVX rats. The DZW-H group showed that serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels reduced by 152.25% (p < 0.01) and osteocalein (OCN) levels dose dependently increased by 118.43% (p < 0.01) as compared with the OVX group. Compared with the OVX group, the DZW at different three dosages of DZW evidently increased the right femur BMD by 112.43, 114.56 and 116.45%, and dramatically promoted bone quality and bone strength (p < 0.05). Further, immunohistochemical evaluation also showed that DZW administration increased ER expression in uteri (p < 0.01). Conclusions DZW exhibits an anti-osteoporotic effect, probably mediated via phyto-estrogenic effects. It might be a potential herbal alternative for the management of postmenopausal osteoporosis.

Previous studies have suggested that silicon (Si) had positive effects on bone, but such benefits from Si may be dependent on calcium status. Also, several biochemical roles of Si in osteoblastic mineralization, the regulation of gene expression related to bone matrix synthesis, and the decrease in reactive oxygen species and pro-inflammatory mediators were reported, but these effects were mostly shown in cell culture studies. Hence, we tested the effect of Si supplementation on bone status and the gene expression related to bone metabolism and inflammatory mediators in young estrogen-deficient rats under calcium-replete condition (0.5 % diet). Results showed that 15-week supplementation of both high and very high doses of Si (0.025 and 0.075 % diet, respectively) could not restore the ovariectomy (OVX)-induced decrease of bone mineral density (BMD) of vertebrae, femur, and tibia. Also, several bone biochemical markers (ALP, osteocalcin, CTx) and mRNA expression of COL-I, RANKL, IL-6, and TNF-α in femur metaphysis were not significantly changed by Si in OVX rats. However, a very high dose (0.075 %) of Si supplementation significantly increased OPG expression and decreased the ratio of RANKL/OPG in mRNA expression comparable to that of sham-control animals. Taken together, Si supplementation did not increase BMD under calcium-replete condition but the decrease in the ratio of RANKL/OPG expression to the normal level suggests the possibility of a bone health benefit of Si in estrogen deficiency-induced bone loss.

The purpose of this study was to evaluate the effects of withdrawal of minodronic acid (MIN) for 3 months after 12 months of treatment in ovariectomized (OVX) rat. OVX rats were orally treated with MIN (6, 30, and 150 µg/kg/day) for 12 months and necropsied on the day after the last dosing or following 3 months of withdrawal. Lumbar and femoral BMD were decreased in OVX controls. MIN dose-dependently increased BMD. Withdrawal eliminated the effect of MIN on BMD loss after treatment at 6 µg/kg, but not after treatment at 30 and 150 µg/kg. In MIN-treated rats, trabecular thinning occurred during withdrawal after treatment at 6 µg/kg, but the trabecular microstructure was maintained at 30 and 150 µg/kg. In a mechanical test of the femoral diaphysis, stiffness of in OVX controls was decreased but ultimate load was similar to that in sham after withdrawal. MIN increased ultimate load and stiffness, but endosteal length decreased after withdrawal. Suppression of bone turnover by MIN based on bone turnover markers and histomorphometric indices was attenuated by withdrawal after treatment at 6 and 30 µg/kg and partially at 150 µg/kg. The MIN concentration in the humerus decreased during withdrawal, and half-life at 30 µg/kg was shorter than that at 150 µg/kg. These results show that the antiresorptive action of MIN was dose-dependently attenuated by 3-month withdrawal in a rat OVX model. An absence of BMD increase was only observed at a low dose but decreases in antiresorptive activity occurred over a wide dose range.

Objectives: Fish proteins are potential sources of natural medicines and food additives. There are many studies being performed to develop underutilized fish proteins. Therefore, the aim of this study was to determine how shark protein functions as a dietary supplement for bone health., Methods: Three groups of ovariectomized (OVX) rats were fed different diets containing 20% casein protein, 20% shark protein, or 20% cod protein for 4 wk. Bone mineral density of the right femur was measured by dual-energy x-ray absorptiometry and quantitative computed tomography. Furthermore, we prepared low-molecular-weight peptides from shark protein using protease for in vitro studies. Calcitriol was added to bone marrow cells and the receptor activator of the nuclear factor-κB ligand was added to RAW264 cells. After 7 d, the number of tartrate-resistant acid phosphatase-positive cells was counted., Results: In the shark protein-fed group, bone mineral density of the femur epiphysis was higher than that of the casein protein-fed group. In particular, the shark protein-fed group showed an increase in bone mineral density, represented mainly by trabecular bone. Shark protein hydrolysates inhibited osteoclast formation in bone marrow cells and RAW264 cells., Conclusions: These results suggest that shark protein might suppress the bone loss caused by estrogen deficiency through the suppression of osteoclast formation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Osteoporosis represents a prevalent disease that involves the degeneration of bone. The development of potent therapies is desired because the current clinical treatments are not able to provide a satisfying therapeutic effect. Recently, gold (Au) nanomaterials and chondroitin sulfate (CS) have been attracted a lot of attention in the field of drug delivery. The purpose of this research was to investigate exactly CS-AuNP function and its positive influences on anti-osteoporosis in ovariectomized (OVX) rats. The outcome of the OVX rats experimental results revealed effective anti-osteoporosis molecular targets of developed CS-AuNP formulation and their influence on the gut microbiota. Importantly, CS-AuNPs significantly improved lipid profiles, bone microstructure, metabolism markers, and bone mineral density. The findings provide more evidence that CS-AuNPs have effective therapeutic potential in anti-osteoporotic treatment by the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Bone broth has recently gained worldwide recognition as a superfood that supplements several nutrients lacking in modern human diets; however, little is known of its efficacy on osteoporosis. Therefore, we aimed to identify the components of chicken–vegetable bone broth (CVBB) that are associated with osteoporosis prevention and verified the efficacy of these components using in vivo studies. In biochemical and cell biological experiments, CVBB was fractionated using ion exchange chromatography (IEC), and the effect of each IEC fraction on osteoclast differentiation was evaluated based on tartrate‐resistant acid phosphatase (TRAP) activity, TRAP staining, and quantitative polymerase chain reaction analysis using mouse macrophage‐like cells (RAW264 cell). In animal experiments, an ovariectomized (OVX) rat model was generated, followed by whole bone broth (OVX/CVBB) or IEC fraction (OVX/CVBB‐Ext) administration and bone structural parameter characterization of OVX rat tibia based on micro‐CT. Four CVBB fractions were obtained using IEC, and the fraction containing both hyaluronan and chondroitin sulfate (CVBB‐Ext) led to the maximum inhibition of RAW264 cell differentiation. CVBB‐Ext downregulated the expression of osteoclast differentiation marker genes. In animal experiments, the OVX group showed a clear decrease in bone density compared to that in the Sham operation group. The OVX/CVBB and OVX/CVBB‐Ext groups showed increased bone mineral density and bone volume/tissue volume values compared to those in the OVX/control group. These results suggested that CVBB and CVBB‐Ext slowed osteoporosis progression. Therefore, we conclude that hyaluronan and chondroitin sulfate in CVBB are key substances that impede osteoporosis progression. Practical Application: This study provides practical information on the effects of bone broth ingredients on osteoporosis to expand the current knowledge on the efficacy of bone broth, which is a widely consumed food. These results may help in the future development of bone broth as a dietary supplement for managing osteoporosis. [ABSTRACT FROM AUTHOR]

Context Studies using experimental models have demonstrated that prebiotics are involved in antiosteoporotic mechanisms. Objective This study was conducted to determine the impact of supplementation with prebiotics in the basal diet of ovariectomized rats with induced osteoporosis as a preclinical model. Methods A comprehensive systematic search was carried out in the electronic databases PubMed, Science Direct, Web of Science, Scielo, and Google through March 2022 for studies that investigated the impact of prebiotics on bone mineral density (BMD), bone mineral content (BMC), and bone biomechanics. Results The search returned 844 complete articles, abstracts, or book chapters. After detailed screening, 8 studies met the inclusion criteria. Rats (n = 206), were randomly divided between control and treatment groups. Weighted mean differences (WMDs) with the 95%CIs were used to estimate the combined effect size. Compared with the control group, dietary intake of prebiotics significantly increased bone density in the BMD subgroups, with WMDs as follows: 0.03 g/cm3, 95%CI, 0.01–0.05, P  < 0.00001, n = 46; and 0.00 g/cm2, 95%CI, 0.00–0.02, P  < 0.00001, n = 81; total BMD: WMD, 0.01, 95%CI, 0.01–0.02, P  < 0.00001, n = 127; bone content in BMC: WMD, 0.02 g, 95%CI, 0.00–0.04, P  = 0.05, n = 107; and the 3-point-bend test: WMD, 15.20 N, 95%CI, 5.92–24.47, P  = 0.00001, n = 120. Conclusion Prebiotics improve indicators of osteoporosis, BMD, BMC, and bone biomechanics in ovariectomized rats. More studies are needed to increase the level of evidence. Systemic Review Registration Systematic Review Protocol for Animal Intervention Studies [ABSTRACT FROM AUTHOR]

Research shows that the consumption of soybean foods can reduce the incidence rate of bone fractures in women after menopause. The aim of this study was to investigate the effects of different complex of soy β‐conglycinin (7S) and isoflavones (7S‐ISO) on osteoporosis in ovariectomized rats. All treatments were administrated intragastrically to the groups every afternoon for 3 months. The treatments were administrated at 1 mL·(100 g)−1, the animals were given 50 mg·kg−1·d−1 ISO, and the concentration of protein was about 2 wt. %. The bone mineral density (BMD) and the bone biomechanics results of left tibia' maximum load in the 7S‐ISO group is significantly higher than in the ovariectomized group and the 7S group (p <.05). Otherwise, the serum tartrate‐resistant acid phosphatase (s‐TRACP), serum osteocalcin (s‐BGP), and serum estradiol (s‐E2) levels in 7S‐ISO were all significantly different from the OVX, OVX + casein, and the OVX + 7S group (p <.05). The serum calcium (s‐Ca) level was not significantly different among all the groups. 7S‐ISO may exhibit moderate estrogenic activities and as compared to 7S and ISO in osteoporosis (OP) of ovariectomized rats. Practical applications: The effects of soy proteins on the health of females have always been a concern. It has been extensively reported soy 7S globulin (7S) as a type of trimer glycoprotein can depress blood fats. The aim of this study was to investigate the effects of different complex of soy β‐conglycinin and isoflavones (ISO), the main storage proteins and polyphenols in soy, on osteoporosis in ovariectomized rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Paeonol can inhibit inflammation and relieve the clinical symptoms of chronic osteoarthritis. As a natural drug component with less side effects and more safety, it is of great clinical significance to explore the treatment of osteoporosis. OBJECTIVE: To investigate the effects of paeonol on the signal pathway of forkhead box O3a/Wnt and the density of vertebrae in ovariectomized osteoporosis (OVX-OP) rats. METHODS: Female Sprague-Dawley rats were randomly divided six groups (n=10 per group). Rats in the sham operation only underwent removal of adipose tissue adjacent to the ovary, and the other 50 rats were used to make OVX-OP rat models by bilateral ovariectomy. The rat models were randomly divided into OVX-OP group, estrogen group (ethinylestradiol 10 μg/kg/d), low- (paeonol 125 mg/kg/d), medium- (paeonol 250 mg/kg/d), and high-dose (paeonol 500 mg/kg/d) groups. The rats were administered by gavage. Sham operation group and OVX-OP group were given the same amount of normal saline. The intervention lasted for 12 weeks. The levels of serum estrogen, osteoprotegerin and osteocalcin were measured by enzyme-linked immunosorbent assay. Bone mineral density of the femur and vertebrae was measured by dual energy X-ray animal bone mineral density meter. The biomechanical indexes of the femur and vertebrae, elastic modulus, maximum load and yield load, were measured by orthopedic biomechanical tester. The expression levels of forkhead box O3a and Wnt2 mRNA were detected by real-time fluorescence quantitative PCR. The expression levels of forkhead box O3a, Wnt2 and nucleus β-catenin proteins were detected by western blot. RESULTS AND CONCLUSION: After the treatment, the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels, and nucleus β-catenin protein level were significantly lower in the OVX-OP group than the sham operation group (P < 0.05), while serum osteocalcin and vertebral forkhead box O3a mRNA and protein levels were significantly higher in the OVX-OP group (P < 0.05). Compared with the OVX-OP group, low-, medium, and high-dose paeonol significantly increased the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels in the vertebrae (P < 0.05), and decreased the levels of serum osteocalcin and vertebral FOXO3a mRNA and protein (P < 0.05). Moreover, the above-mentioned indexes were better in the high-dose paeonol group than the estrogen group (P < 0.05). To conclude, paeonol can increase bone mineral density of the vertebrae, improve the biomechanical condition, and relieve osteoporosis in OVX-OP rats, which may be related to the inhibition of forkhead box O3a and the promotion of Wnt2/β-catenin pathway activation. [ABSTRACT FROM AUTHOR]

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes. Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the impact of eggshell calcium (Biomin H® dietary supplement) and its combinations with alfacalcidol (1α‐hydroxyvitamin D3) and menaquinone‐7 (vitamin K2) on ovariectomy‐induced bone loss in rats. Adult female rats (n = 48) were divided into 6 groups of 8 individuals each: sham‐operated rats (SHAM); ovariectomized (OVX) rats untreated; OVX rats treated with Biomin H® (BIO); OVX rats simultaneously receiving Biomin H®, vitamin D3 (BIO + D3); OVX rats simultaneously treated with Biomin H®, vitamin K2 (BIO + K2) and OVX rats treated with Biomin H®, vitamin D3, vitamin K2 (BIO + D3 + K2) during 8 weeks. Biochemical parameters, bone mineral density (BMD), bone mineral content (BMC) and femoral bone microstructure were determined. Plasma calcium and phosphate were increased in BIO + D3 and BIO + D3 + K2 groups as compared to OVX. Alkaline phosphatase was elevated in OVX, BIO versus SHAM, BIO + D3 + K2 groups. When compared to OVX group, decreased urine deoxypyridinoline was observed in all treated groups and femoral BMD, BMC were higher in BIO, BIO + D3, BIO + D3 + K2 groups. The BIO + K2 rats had similar densitometrical values than OVX individuals. Microcomputed tomography revealed increased trabecular relative bone volume (due to an increase in trabecular number) in BIO + D3, BIO + D3 + K2 as compared to OVX. The higher relative bone volume in BIO + D3, BIO + D3 + K2 groups was also accompanied by an increase in bone surface. In the cortical bone, an enhanced periosteal bone apposition was identified in BIO, BIO + D3, BIO + K2, BIO + D3 + K2 groups. The rats from BIO + D3 + K2 group had a higher area of primary osteon's vascular canals. In BIO + D3, BIO + K2, BIO + D3 + K2 groups, an increased area of secondary osteons was determined in comparison with OVX. Our results indicate the beneficial effect of triple application of Biomin H®, vitamin D3, vitamin K2, as well as simultaneous administration of Biomin H®, vitamin D3 on the inhibition of ovariectomy‐induced bone loss in a rat model of osteoporosis. [ABSTRACT FROM AUTHOR]

Estrogen, produced mainly in the ovaries, plays a role in sexual development, metabolism, and bone formation. Thus, estrogen deficiency due to menopause can lead to overweight, dyslipidemia, and osteoporosis. In this study, we compared the effects of extracts of Sargassum fusiforme, Pueraria lobata, and their mixtures at various ratios on osteosarcoma SaOS-2 cells and investigated the effect of PS31 (P. lobata: S. fusiforme = 3:1, KGC02PS) on postmenopausal symptoms in ovariectomized rats. PS31 supplementation, as little as 100 mg/kg BW, effectively reduced ovariectomy-induced weight gain, and total triglyceride, total cholesterol, and low-density lipoprotein-cholesterol concentrations in serum. In addition, PS31 supplementation prevented bone density loss, inhibited bone resorption, and reduced the expression of catabolic factors in bone. However, PS31 supplementation did not affect uterus weight and expression of c-Jun and c-Fos, which suggests that the mechanism of action of PS31 is distinct from that of estrogen. Taken together, we demonstrated that PS31 supplementation alleviated postmenopausal symptoms, including overweight, dyslipidemia, and osteoporosis. Therefore, PS31 could be potentially used as food supplement to prevent postmenopausal symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Postmenopausal osteoporosis and dyslipidemia are well-known skeletal and metabolic changes in middle-aged women. We investigated the effects of combined treatments with a selective estrogen receptor modulator (SERM) and exercise on bone and fat parameters in ovariectomized (OVX) rats.Materials and Methods: Sixteen-week-old female Sprague-Dawley rats underwent bilateral ovariectomy, and rats were randomized to BZA (bazedoxifene at 0.3 mg/kg/day), Exe (treadmill exercise at 12-15 m/min, 60 min/day, 5 days/week), Comb (BZA and Exe), and Cont (control treated with vehicle and no exercise) groups 8 weeks after ovariectomy. After 4 or 8 weeks of treatment, bone mineral density (BMD) of the total femur and lumbar spine and whole-body percentage fat mass were determined by dual-energy X-ray absorptiometry, and mechanical testing of the femoral shaft, and bone and fat histomorphometric analyses of the proximal tibia were performed.Results: Treadmill exercise had decreased bone marrow adipocytes from 4 weeks of treatment and whole-body percentage fat mass at 8 weeks. BZA increased BMD at the lumbar spine and decreased the whole-body percentage fat mass from 4 weeks and bone marrow adipocytes at 8 weeks. Combination therapy increased BMD for the lumbar spine and decreased bone marrow adipocytes and whole-body percentage fat mass from 4 weeks.Conclusion: Combination therapy with BZA and exercise appears effective to improve bone and fat parameters in OVX rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Apigenin has been shown to hold the effects of antivirus, anti-inflammation, anti-oxidation and tranquilizer and sedative. OBJECTIVE: To study the effect of different doses of apigenin on osteoporosis in rats and to explore the underlying mechanism. METHODS: The study was approved by the Laboratory Animal Ethical Committee of Southern Medical University. Forty-two adult male Sprague-Dawley rats were selected, and the rat models of osteoporosis were established by ovariectomy. The rats were divided into seven groups (n=6/group): the sham operation group, the control group, the positive control group, and the 20, 40, and 60, and the 80 mg/kg apigenin groups according to the dose of apigenin. The sham operation group did not receive the removal of the ovaries. The positive control group was supplemented with diethylstilbestrol (0.02 mg/kg), vitamin D and calcium daily. The control group was given the subcutaneous injection of same volume of purified water. The apigenin groups were given the subcutaneous injection of various doses of apigenin, respectively, once daily, for 8 weeks. The femoral bone mineral density and serum levels of calcium, phosphorus, bone alkaline phosphatase, amino-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen were measured at 4 and 8 weeks after intervention, respectively. RESULTS AND CONCLUSION: (1) Compared with the control group, when the dose of apigenin was 40, 60 and 80 mg/kg, the bone mineral density, and serum levels of calcium and phosphorus were increased significantly at 4 and 8 weeks (P < 0.05), and the levels of amino-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen and bone alkaline phosphatase were decreased significantly (P < 0.05). (2) Compared with the positive control group, when the dose of apigenin was 60 and 80 mg/kg, the bone mineral density, serum levels of calcium and phosphorus, the levels of amino-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen and bone alkaline phosphatase showed no significant difference at 4 and 8 weeks (P > 0.05). When the dose of apigenin was 20 and 40 mg/kg, compared with the positive control group, the bone mineral density, and serum levels of calcium and phosphorus were decreased significantly at 4 and 8 weeks (P < 0.05), and the levels of amino-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen and bone alkaline phosphatase were increased significantly (P < 0.05). (3) Compared with the sham operation group, in the control group, the bone mineral density, and serum levels of calcium and phosphorus were decreased significantly at 4 and 8 weeks (P < 0.05), and the levels of amino-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen and bone alkaline phosphatase were increased significantly (P < 0.05). (4) These results suggest that it is indeed effective to establish a rat osteoporosis model by ovariectomy. The therapeutic effect of apigenin on osteoporosis is dose-related, and a certain dose of apigenin has an anti-osteoporosis effect. [ABSTRACT FROM AUTHOR]

Purpose: Osteoporosis is one of the major health concerns among the elderly population, especially in postmenopausal women. Many menopausal women over 50 years of age lose their bone density and suffer bone fractures. In addition, many mortality and morbidity cases among the elderly are related to hip fracture. This study aims to investigate the effect of Lactobacillus helveticus (L. helveticus) on bone health status among ovariectomized (OVX) bone loss-induced rats. Methods: The rats were either OVX or sham OVX (sham), then were randomly assigned into three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108–109 colony forming units). The supplementation was force-fed to the rats once a day for 16 weeks while control groups were force-fed with demineralized water. Results: L. helveticus upregulated the expression of Runx2 and Bmp2, increased serum osteocalcin, bone volume/total volume and trabecular thickness, and decreased serum C-terminal telopeptide and total porosity percentage. It also altered bone microstructure, as a result increasing bone mineral density and bone strength. Conclusion: Our results indicate that L. helveticus attenuates bone remodeling and consequently improves bone health in OVX rats by increasing bone formation along with bone resorption reduction. This study suggests a potential therapeutic effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Achyranthes bidentata is an important Traditional Chinese Medicine for the treatment of osteoporosis. In this study, A. bidentata polysaccharide (ABPB), which was extracted with alkali from the root of A. bidentata at room temperature, significantly increased the bone mineral density, bone mineral content, trabecular thickness, trabecular number and biomechanical properties of ovariectomized (OVX) rats, indicating that ABPB had prominent curative effects on osteoporosis in OVX rats. A novel polysaccharide (ABPB-3) was purified from ABPB, and its structure was characterized as a repeating unit consisting of →4)- α - d -Gal p A-(1→, →2,4)- α - l - R ha p -(1→, →5)- α - l -Ara f -(1→, →2,3,5)- α - l -Ara f -(1→, →3)- β - d -Gal p -(1→, →3,4,6)- β - d -Gal p -(1→, terminated with α - l -Ara f , α - l - R ha p and β - d -Gal p . Up to now, there were no literature reports relevant to the structure of ABPB-3. In the zebrafish model of glucocorticoid-induced osteoporosis (GIOP), ABPB-3 significantly increased the relative fluorescence intensity of the skull bone mass in a concentration-dependent manner, indicating that it stimulated bone formation activity. Thus, ABPB and ABPB-3 have the potential to be used for the anti-osteoporosis medicine. [ABSTRACT FROM AUTHOR]

Objective To investigate the evolution characteristics of bone microstructure in rats with diabetes combined with castration. Methods Forty 6-month-old female SD rats were randomly divided into sham operation group,castration group,diabetes mellitus group,and diabetes combined with castration group. Bone mineral density and bone microstructure of the femurs were measured using micro-CT after 6 weeks and 15 weeks. Deposition changes of collagen fiber were observed by van Gieson collagen staining. The changes of the trabecular thickness (Tb.Th) and the trabecula separation (Tb.Sp) were analyzed by HE staining. Results Compared with the sham group,the levels of bone β-collagen degradation products and Tb.Sp significantly increased,bone mineral density and Tb. Th significantly decreased,and the differences were statistically significant (P<0.05) in the 6-week and 15-week castration group. The levels of β-collagen degradation products and Tb. Sp significantly increased,bone mineral density and Tb. Th significantly decreased,and the collagen decreased in the 15-week castration group.The difference was statistically significant (P<0.05) in the 15-week diabetes mellitus group. The levels of β-collagen degradation products and Tb. SP significantly increased,bone mineral density,collagen,and Tb.Th significantly decreased,and the differences were statistically significant (P<0.05) in the 6-week and 15-week diabetes combined with castration group. Conclusion In the early stage of diabetes mellitus combined with castration,osteoporosis is mainly caused by castration. However,in the later period,osteoporosis continues to develop due to slow bone decomposition of diabetes. [ABSTRACT FROM AUTHOR]

Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of Artemisia princeps (AP) extract on bone metabolism and its potential role in the prevention of osteoporosis in ovariectomized rats. Twenty-six female Sprague-Dawley rats were divided into five groups and treated as follows: sham-operated control group (SHAM); ovariectomized control group (OVX), ovariectomized group treated by gavage with 10 mg/kg/day alendronate (ALEN); ovariectomized group treated by gavage with 100 mg/kg/day Artemisia princeps (AP100); ovariectomized group treated by gavage with 300 mg/kg/day Artemisia princeps (AP300). Treatment of ovariectomized rats with AP extracts for 15 weeks prevented the reduction in bone thickness and trabecular bone mineral density caused by urinary Ca and Cr excretion, and also prevented the increase in bone turnover by maintaining the serum Ca/P ratio. As a result, the microarchitecture of the trabecular bone and cortical bone after ovariectomy was markedly improved by administration of AP extracts. In conclusion, AP prevented bone loss and osteoclast activity associated with high bone turnover in ovariectomized rats by controlling the serum Ca/P ratio and through anti-inflammatory and anti-oxidant properties. Our data implicate AP as a promising therapeutic option for the improvement of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Antioxidant lycopene supplementation has been shown to decrease oxidative stress and have beneficial effects on bone health. However, it remains unclear whether lycopene exerts its beneficial effect on bone metabolism through mitigation of oxidative stress in vivo. The aim of this study was to investigate whether lycopene intake protects against bone loss by reducing oxidative stress in ovariectomized rats. Female Sprague-Dawley 6-week-old rats were ovariectomized and randomly divided into four groups according to the lycopene content of their diet: 0, 50, 100, and 200 ppm. The tibial bone mineral density (BMD) in the 50, 100, and 200 ppm groups was significantly higher than that in the 0 ppm group. Serum and urinary bone resorption marker levels were significantly lower in the 50, 100, and 200 ppm groups than in the 0 ppm group. There was no significant difference in systemic oxidative stress markers among all groups. However, systemic oxidative stress levels were inversely correlated with the tibial BMD. Our findings suggest that lycopene intake significantly inhibits bone loss by suppressing bone resorption in ovariectomized rats. Further studies are necessary to clarify the effect of lycopene on oxidative stress in local tissues such as bone tissue. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the roles or effects of oviductus ranae (OR) or oviductus ranae eggs (ORE) in preventing and treating postmenopausal osteoporosis. Methods: In vivo experiment: Sixty female adult Wistar rats were randomly divided into 5 groups of 12. To provide an osteoporosis model 4 groups of rats were ovariectomized (OVX), with the 5th being sham operated. Medication commenced 7 days after the operation and lasted continuously for 12 weeks. Sham operated and OVX groups were given equivalent volumes of 5% Tween-80. The other three groups intragastrically received conjugated estrogens (CE), OR or ORE of the corresponding doses. At the 12th week, serum estrogen, bone gla protein (BGP), serum calcium, phosphorus, and alkaline phosphatase (ALP) were assayed; bone mineral densities (BMD) were measured and bone scanning was conducted; uteri were weighed, and weight, volume and length of the femoral bones were determined; and cortical thickness of femoral heads and area of bone trabecula were measured by image analyzer. In vitro experiment: Eighty 10-month old SD rats, with equal numbers of males and females, were randomly divided into 8 groups. Osteoblasts were isolated from neonatal rat calvariae, and the cells were exposed to various concentrations of serum from OR and ORE groups to study the impact of these sera on osteoblastic proliferation, ALP activity and mineralization. Osteoclastic numbers were determined using tartrate resistant acid phosphatase (TRAP). Results: In vivo experiment: The body weight of the four OVX groups increased significantly ( P<0.01). Uterine weight of the CE group was the highest ( P<0.01); Compared with the model group, estrogen level, BMD, bone scanning/bone imaging index weight of the femoral bones, cortical thickness of femoral heads in the OR and ORE groups increased significantly ( P<0.05, P<0.01); femoral volume in the ORE group increased significantly ( P<0.05); and the content of osteocalcin, phosphorus, and ALP in serum decreased significantly ( P<0.05, P<0.01). In vitro experiment: Sera from OR and ORE groups had notable effects on the proliferation of osteoblasts ( P<0.05 and P<0.01, repsectively) and stimulated the formation of calcium nodes ( P<0.05, P<0.01), while the enhancement of ALP activity in osteoblasts was significant ( P<0.05, P<0.01). The number of TRAP-positive cells was significantly reduced as well ( P<0.01). Conclusions: OR and its eggs could effectively suppress OVX-induced osteoporosis in rats, and increase bone turnover possibly by both an increase in osteoblastic activity and a decrease in osteoclastic activity. The present study provides evidence that OR and its eggs could be considered a complementary and alternative medicine for the treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

TAK-778, a derivative of ipriflavone, has been shown to induce bone growth both in vitro and in vivo. Recently, it has been shown that TAK-778 can enhance osteoblast differentiation of human bone marrow cells via an estrogen receptor (ER)-dependent pathway. However, the mechanism by which TAK-778 exerts its effect in vivo has not been determined. Considering the evidence that TAK-778 acts via ER-mediated signaling in vitro, in the present study we tested if TAK-778 induced osteogenesis via an ER-dependent pathway using an ovariectomized (OVX) rat model. Two weeks after test animals underwent ovariectomy, TAK-778 and/or tamoxifen was administered orally over 3 months. Vehicle-treated and sham-operated rats served as controls. The bone mineral density (BMD) of the lumbar vertebrae and sagittal two-dimensional images of the L3 vertebral body were measured. In addition, bone formation rates (BFR) and serum calcium and osteocalcin levels were measured. The results indicated that TAK-778 significantly increased BMD, serum calcium and osteocalcin levels, and BFR when compared to that of the vehicle-treated group. However, tamoxifen, a well-known ER antagonist, clearly inhibited the increase in these parameters induced by TAK-778. In addition, micro-computed tomography scans showed that treatment with TAK-778 increased the structure model index, bone volume/tissue volume, and trabecular thickness parameters and decreased the trabecular separation/spacing in OVX rats. Tamoxifen suppressed these effects when administered in combination with TAK-778. Taken together, the present study showed that TAK-778 enhanced bone formation in OVX rats and that this effect was dependent on an ER-mediated pathway. [ABSTRACT FROM AUTHOR]

Regular activity has effects on bone size, shape, and density, resulting in an increase in mechanical strength. The mechanism of action that underlies this improvement in bone strength is mainly linked to an increase in bone formation. Zoledronic acid (Z), in contrast, may prevent bone strength changes in ovariectomized (OVX) rodents by its potent antiresorptive effects. Based on these assumptions we hypothesized that combined effects of exercise (E) and Z may produce higher benefits on bone changes resulting from estrogen deficiency than either intervention alone. At 6 months of age, 60 female Wistar rats were OVX or sham operated (SH) and divided into five groups: SH, OVX, OVX-E, OVX-Z, and OVX-ZE. OVX rats were treated with a single IV injection of Z (20 microg/kg) or vehicle and submitted or not to treadmill exercise (15 m/min, 60 min/day, 5 days/week) for 12 weeks. Whole-body BMD and bone turnover markers were analyzed longitudinally. At sacrifice, femurs were removed. BMD by DXA, three-point bending test, and microCT were performed to study biomechanical and trabecular structure parameters, respectively. After 12 weeks, bone volume fraction decreased in OVX rats, whereas bone turnover rate, trabecular spacing, and structure model index increased compared with those in the SH group (P < 0.05). Zoledronic acid prevented the ovariectomy-induced trabecular bone loss and its subsequent trabecular microarchitectural deterioration. Treadmill exercise running was shown to preserve the bone strength and to induce bone turnover changes in favor of bone formation. However, the combined effects of zoledronic acid and running exercise applied simultaneously did not produce any synergetic or additive effects. [ABSTRACT FROM AUTHOR]

Abstract: We examined the combined effects of human parathyroid hormone 1–34 (hPTH) and elcatonin (ECT: a synthetic derivative of eel calcitonin) to prevent loss of bone mass, architecture and strength in ovariectomized (OVX) rats. Fifty-four female rats (aged 13 weeks) were assigned to one of nine groups: Sham (fake surgery performed), OVX, ECT (15 U/kg administered), PTH5, PTH10 and PTH20 (5, 10 or 20 μg/kg administered), and E+PTH5, E+PTH10 and E+PTH20 (15 U/kg of ECT and 5, 10 or 20 μg/kg of hPTH administered). The drug or vehicle was subcutaneously administered three times a week for 12 weeks. The femurs were removed at the completion of the experiment. The right distal femoral metaphysis was used for measuring bone mineral density (BMD), analyzing trabecular bone structure by micro-computed tomography (μCT), and conducting the bone strength test, and the left femur was used for histomorphometric analysis. Trabecular bone volume (BV/TV) and other bone mass parameters were greater in the ECT and PTH groups than in the OVX group. The number of nodes (N.Nd/TV) and trabecular number (Tb.N) were significantly greater in the ECT group, and trabecular thickness (Tb.Th) and trabecular bone pattern factor (TBPf) were significantly greater in the PTH group. These results indicate that these drugs preserve the bone architecture by different means. Analysis by means of μCT revealed that BV/TV, Tb.N, fractal D and N.Nd/TV were significantly greater in the E+PTH groups than in the PTH groups at each concentration. Trabecular separation (Tb.Sp) was significantly lower in the E+PTH5 and E+PTH10 groups than in the respective PTH5 and PTH10 groups. When the maximum load was applied in a compression test on the distal femur, the E+PTH groups had higher values than the PTH groups, however, the three point bending strength of the diaphysis of femur in the E+PTH10 and E+PTH20 groups tended to be low compared to those in the PTH10 and PTH20 groups. These results indicate that combination therapy using PTH and ECT preserves the trabecular microarchitecture better than single-drug therapy using ECT or PTH in OVX rats, however, it is necessary to optimize the calcitonin (CT) dosage and administration in order to achieve the optimal combined effect of PTH and CT. [Copyright &y& Elsevier]

Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial. [Display omitted] [ABSTRACT FROM AUTHOR]

Bone mineral turnover was studied in sham and ovariectomized (ovax) retired breeder rats after 16 wk of dietary treatment. Rats were fed either a commercial rat diet (CRD) containing high calcium and cholecalciferol or egg-white diets (EWD) containing 2 g Ca/kg, 1,25-(OH)2cholecalciferol (5 μg/kg), and either 10 or 200 mg zinc/kg. In rats fed EWD, high Zn enhanced femoral Zn deposition and concentration but did not affect serum Ca levels, bone mineral content (BMC), or turnover. Serum Ca levels and BMC were greater in sham rats and there was a gain in femoral Ca and phosphorus compared with the loss ofthese minerals in ovax rats. In CRD-fed ovax rats, values for these variables were similar to those of CRD-fed shams and there was no bone mineral loss. These data suggest that ovarian function may be a prerequisite for the beneficial effects ofdiets containing 1,25-(OH)2cholecalciferol and low Ca on bone metabolism [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), 'Wangbulryuhaeng' in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrate-resistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factor-κB ligand-induced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and c-Fos were measured using western blotting and reverse transcription-PCR. The expression levels of osteoclast-related genes were also examined. To further investigate the anti-osteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using micro-computed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclast-related genes by downregulating transcription factors, such as NFATc1 and c-Fos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosis-like symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Size reduction of YBP promoted protein digestion instead of Ca2+ and P5+ release. • The anti-osteoporosis effect of YBP involved B-ALP, OCN, S-CTX, ES and TRAP. • No relationship between YBP size and its anti-osteoporosis efficiency was observed. As a kind of promising resource, animal bone has been widely processed into functional foods. However, there is little research about the effect of particle size on the physicochemical properties and digestibility of yak bone powder (YBP), as well as its anti-osteoporosis activity. In this study, the YBP with median particle sizes (MPS) ranging from 19.68 to 128.37 μm were prepared, and their digestibility and anti-osteoporosis activity were investigated. The results showed that smaller MPS significantly increased water holding capacity and protein solubility without changing composition. The MPS reduction greatly promoted protein digestion, producing more peptides<3 kDa and free amino acids while decreased Ca2+ and P5+ release during gastrointestinal digestion. The in vivo results revealed the positive effect of YBP on ovariectomy-induced osteoporosis in rats. The bone mineral density of ovariectomized (OVX) rats was obviously improved by regulating bone turnover markers (B-ALP, OCN, S-CTX, ES and TRAP), thus potentially shedding light on osteoporosis remission. However, different MPS exhibited a weak effect on osteoporosis in OVX rats. Therefore, YBP could be produced in relatively large particle size without sacrificing food sensory quality, the processing time of which could also be shortened for higher productivity and lower cost. [ABSTRACT FROM AUTHOR]

• miR-141 overexpression improved osteoporosis of jawbones in ovariectomized rats. • miR-141 overexpression decreased RANKL, BGP and TRAP levels in serum. • miR-141 overexpression increased Runx2 and OSX expression in jawbones. • miR-141 regulated Wnt/β-catenin pathway in jawbones of ovariectomized rats. This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/β-catenin pathway. Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, β-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/β-catenin pathway. Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and β-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05). Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]