Bone Loss In Ovariectomized Rats Research Articles

Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats.

Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague–Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU–DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis.

Genistein in Combination with Fructooligosaccharides Prevents Bone Loss in Ovariectomized Rats

Osteoporosis is an age‐related chronic condition characterized by low bone mineral density, especially in postmenopausal women. Certain nutritional factors can reduce the risk of osteoporosis and thereby reduce the risk of fractures. Isoflavones are compounds found in plants such as soy that are structurally similar to estrogen. Geniestein and daidzein are the two important soy isoflavones which may play a role in prevention of bone loss. These isoflavones may have superior health benefits in presence of prebiotics such as fructooligosaccharides (FOS). The current study was designed to examine the bone protective effects of genistein and daidzein in the presence and absence of FOS in an ovariectomized (Ovx) rat model of osteoporosis. For this purpose, three month‐old female Sprague‐Dawley rats were either sham‐operated (Sham) or Ovx to induce bone loss. Rats were divided into seven groups with 12 rats per group: group 1 (Sham, control diet), group 2 (Ovx, control diet), group 3 (Ovx, daidzein‐rich isoflavones; 5 μg/g body weight), group 4 (Ovx, genistein‐rich isoflavones; 5 μg/g body weight), group 5 (Ovx, genistein‐rich isoflavones + FOS; 5 μg/g body weight), group 6 (Ovx, daidzein‐rich isoflavones; 10 μg/g body weight), and group 7 (Ovx, genistein‐rich isoflavones; 10 μg/g body weight). Animals were fed a semi‐synthetic‐powdered AIN‐93M diet. The dietary treatments began immediately after surgery and continued for 50 days, a period sufficient to detect treatment effects. Bone mineral content (BMC) and density (BMD) of whole body, tibia, femur, and 4th lumbar vertebra were measured using dual energy X‐ray absorptiometry. Additionally, serum osteocalcin, serum total alkaline phosphatase (ALP), and urinary deoxypyridinoline (Dpd) were assessed. As expected, Ovx resulted in significant bone loss compared to the Sham. Ovx rats that received genistein plus FOS had significantly higher whole body BMD (P<0.05) in comparison to Ovx control rats. Additionally, genistein plus FOS completely prevented loss of 4th lumbar vertebral and left tibial BMD (P<0.05). The results suggest that genistein plus FOS prevented bone loss, in part, by maintaining high rate of bone formation as evidenced by higher serum levels of ALP and osteocalcin. The overall findings of this study suggest that beneficial effect of genistein on bone is profoundly affected by FOS; however, the mechanism of action needs further investigation.

Effects of alendronate on lumbar intervertebral disc degeneration with bone loss in ovariectomized rats

Background ContextOsteoporosis adversely affects disc degeneration cascades, and prophylactic alendronate (ALN) helps delay intervertebral disc degeneration (IDD) in ovariectomized (OVX) rats. However, there remains no information regarding whether ALN affects IDD with bone loss. PurposeThis study aimed to observe the effects of ALN on degenerative discs with bone loss induced by OVX in rats. Study DesignThis study used controlled in vivo experiments in rodents. MethodsThirty female Sprague-Dawley rats were randomly assigned to undergo sham surgery (n=10) or OVX surgery (n=20); 3 months later, the OVX animals were injected with either ALN (OVX+ALN, 15 µg/kg/2w, n=10) or normal saline (OVX+vehicle treatment [V], n=10). At 3 months after the ALN intervention, van Gieson staining and immunohistochemistry were used to investigate histologic and metabolic changes in the discs. Bone mineral density (BMD), micro-computed tomography, and biomechanical tests were conducted to determine the biological properties of the vertebrae. ResultsThe OVX+ALN group exhibited significantly reduced morphologic degenerative alterations in both the nucleus pulposus and annulus fibrosus, with a markedly lower IDD score than that of the OVX+V group. The OVX+ALN samples showed increased disc height and decreased cartilage end plate thickness and bony area compared with the OVX+V group. Compared with saline, ALN administration markedly inhibited the type I collagen, matrix metalloprotease (MMP)-1, and MMP-13 expression levels while increasing the type II collagen and aggrecan expression levels in the disc matrix. Compared with the OVX+V group, OVX+ALN vertebrae revealed significantly enhanced BMD with increased biomechanical strength, as well as increased percent bone volume and trabecular thickness. ConclusionsALN has favorable effects on disc degeneration with bone loss and helps to alleviate IDD while enhancing the biological and mechanical properties of vertebrae and end plates.

Psoralidin, a prenylated coumestan, as a novel anti-osteoporosis candidate to enhance bone formation of osteoblasts and decrease bone resorption of osteoclasts

Traditional Chinese medicines (TCM) have been proven to prevent osteoporosis, but their clinical applications are not widely recognized due to their complicated ingredients. Psoralidin, a prenylated coumestan, has been reported to prevent bone loss of ovariectomized rats, but detailed mechanisms are still not clear. In current study, we found that both psoralidin and coumestrol promoted osteoblast proliferation and differentiation, as evidenced by improvements in cell proliferation and alkaline phosphatase activity; increased formation of ALP colonies and calcified nodules; enhanced secretion of collagen-I, BMP-2, osteocalcin and osteopontin; and stimulation of the expression of IGF-1, β-catenin, Runx-2, Osterix, and OPG, as well as the mRNA ratio of OPG/RANKL, while significantly decreasing the expression of RANKL. In addition, both psoralidin and coumestrol inhibited osteoclast formation and osteoclastic bone resorption, as demonstrated by the lower tartrate-resistant acid phosphatase activity and smaller area, with fewer resorption pits formed. Interestingly, psoralidin showed much stronger effects than coumestrol at enhancing osteoblast proliferation/differentiation or inhibiting osteoclast differentiation and bone resorption. Moreover, we found that both psoralidin and coumestrol suppressed COX-2 and ROS production in rat osteoblastic calvarias cells, and psoralidin showed stronger effects than coumestrol. Furthermore, we detected that by blocking estrogen receptors with ICI 182.780 (an estrogen receptor antagonist), the osteoprotective effects of psoralidin and coumestrol were also blocked. Our findings demonstrated that psoralidin and coumestrol exert their bone-protective effects by enhancing bone formation of osteoblasts and inhibiting bone resorption of osteoclasts. These roles might be mediated by their antioxidant activity and transduced through estrogen receptor signaling.

Extracorporeal shock waves alone or combined with raloxifene promote bone formation and suppress resorption in ovariectomized rats.

Osteoporosis is a metabolic skeletal disease characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. We examined the beneficial effect of shock waves (SW) alone or in combination with raloxifene (RAL) on bone loss in ovariectomized rats (OVX). Sixteen weeks after surgery, OVX were treated for five weeks with SW at the antero-lateral side of the right hind leg, one session weekly, at 3 Hz (EFD of 0.33 mJ/mm2), or with RAL (5 mg/kg/die, per os) or with SW+RAL. Sera, femurs, tibiae and vertebrae were sampled for following biochemical and histological analysis. SW, alone or combined with RAL, prevented femur weight reduction and the deterioration of trabecular microarchitecture both in femur and vertebrae. All treatments increased Speed of Sound (SoS) values, improving bone mineral density, altered by OVX. Serum parameters involved in bone remodeling (alkaline phosphatase, receptor activator of nuclear factor kappa-B ligand, osteoprotegerin) and osteoblast proliferation (PTH), altered by ovariectomy, were restored by SW and RAL alone or in combination. In tibiae, SW+RAL significantly reduced cathepsin k and TNF-α levels, indicating the inhibition of osteoclast activity, while all treatments significantly increased runt-related transcription factor 2 and bone morphogenetic-2 expression, suggesting an increase in osteoblastogenic activity. Finally, in bone marrow from tibiae, SW or RAL reduced PPARγ and adiponectin transcription, indicating a shift of mesenchymal cells toward osteoblastogenesis, without showing a synergistic effect. Our data indicate SW therapy, alone and in combination with raloxifene, as an innovative strategy to limit the hypoestrogenic bone loss, restoring the balance between bone formation and resorption.

Puerarin and zinc additively prevent mandibular bone loss through inhibiting osteoclastogenesis in ovariectomized rats.

Puerarin and zinc play a key role in preventing osteoporotic-related bone loss. Previous research on puerarin or zinc mainly focused on the anti-osteoporotic effects of long bone. However, it is obscure for puerarin or zinc to prevent mandibular osteoporosis. Here, we explore the effects on additive coadministration of puerarin and zinc on preventing mandibular bone loss in ovariectomized rats, and evaluate the underlying mechanisms ex vivo. Rats were ovariectomized and administrated puerarin, zinc or both. After 12 weeks, bone mineral density (BMD) and histomorphometry of mandibles were measured by micro-CT. The mechanical properties were determined using a three-point bending test. Then, osteogenic differentiation of primary bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow mononuclear were performed ex vivo. The culture supernatant and serum level of bone biochemical markers including osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were detected by ELISA. Culture supernatant and serum levels of calcium were measured using a Plasma Emission Spectrometer. One-way ANOVA was used for statistical analyses. The results showed that administration of puerarin plus zinc prevented the decrease in mandibular BMD and bone morphometrical parameters more effectively than single use of puerarin or zinc (p<0.05), which was similar to the biomechanical tests (p<0.05). Furthermore, puerarin and zinc additively up-regulated OPG, OPN protein levels, Ca ion level and down-regulated RANKL, TRAP protein levels. In conclusion, puerarin and zinc additively prevent mandibular bone loss through inhibiting osteoclastogenesis in ovariectomized rats, which will shed more light on the potential use of puerarin and zinc in the prevention/treatment of oral bone loss clinically.

Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats

Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis.

Methoxyisoflavones formononetin and isoformononetin inhibit the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions.

Recent studies have shown that immune system plays a major role in pathophysiology of postmenopausal osteoporosis. Previously we have shown that phytoestrogens like daidzein and medicarpin exhibit immunoprotective effects, by virtue of which they alleviate bone loss. With this background, methoxyisoflavones like formononetin (formo) and isoformononetin (isoformo) that have been studied for preventing bone loss in ovariectomized rats were tested for their immunomodulatory effects in estrogen-deficient bone loss mice model. Adult Balb/c mice (N = 8/group) were given oral dose of formo and isoformo at 10 mg/kg body weight, post ovariectomy (Ovx) daily for 6 weeks. Animals were autopsied and long bones were harvested to study bone microarchitecture. Peripheral blood mononuclear cells were isolated for fluorescence-activated cell sorting and RNA analysis. Serum was collected for enzyme-linked immunosorbent assay. It was observed that formo and isoformo treatment to Ovx mice led to significant restoration of Ovx-induced deterioration of trabecular microarchitecture. Pro-osteoclastogenic subset Th17 and B cells were decreased in formo/isoformo-treated Ovx mice in comparison with vehicle-treated Ovx group. Formo and isoformo treatment to Ovx mice also led to decreased expression of Th17 diffentiation factors and promoted T-regulatory cell differentiation. Formo was more effective in enhancing the FOXP3 expression compared with isoformo. IL-17A-induced osteoclastogenesis and inhibition of osteoblast apoptosis were also suppressed by formo and isoformo treatment, with formo having a more potent effect. Our study demonstrates the immunomodulatory activity of methoxyisoflavones, formo, and isoformo, which translate into improved skeletal parameters, thereby preventing Ovx-induced bone loss.

Spaceflight-induced vertebral bone loss in ovariectomized rats is associated with increased bone marrow adiposity and no change in bone formation.

There is often a reciprocal relationship between bone marrow adipocytes and osteoblasts, suggesting that marrow adipose tissue (MAT) antagonizes osteoblast differentiation. MAT is increased in rodents during spaceflight but a causal relationship between MAT and bone loss remains unclear. In the present study, we evaluated the effects of a 14-day spaceflight on bone mass, bone resorption, bone formation, and MAT in lumbar vertebrae of ovariectomized (OVX) rats. Twelve-week-old OVX Fischer 344 rats were randomly assigned to a ground control or flight group. Following flight, histological sections of the second lumbar vertebrae (n=11/group) were stained using a technique that allowed simultaneous quantification of cells and preflight fluorochrome label. Compared with ground controls, rats flown in space had 32% lower cancellous bone area and 306% higher MAT. The increased adiposity was due to an increase in adipocyte number (224%) and size (26%). Mineral apposition rate and osteoblast turnover were unchanged during spaceflight. In contrast, resorption of a preflight fluorochrome and osteoclast-lined bone perimeter were increased (16% and 229%, respectively). The present findings indicate that cancellous bone loss in rat lumbar vertebrae during spaceflight is accompanied by increased bone resorption and MAT but no change in bone formation. These findings do not support the hypothesis that increased MAT during spaceflight reduces osteoblast activity or lifespan. However, in the context of ovarian hormone deficiency, bone formation during spaceflight was insufficient to balance increased resorption, indicating defective coupling. The results are therefore consistent with the hypothesis that during spaceflight mesenchymal stem cells are diverted to adipocytes at the expense of forming osteoblasts.

Olive oil exhibits osteoprotection in ovariectomized rats without estrogenic effects.

The present study was designed to evaluate the effect of olive oil on bone and uterus in ovariectomized rats. A total of 34 surgically ovariectomized or sham-operated virgin Sprague-Dawley rats were divided into four groups: i) Sham-operated control rats (sham group); ii) Ovariectomized rats (OVX group); iii) Olive oil-supplemented ovariectomized rats (olive group); and iv) Diethylstilbestrol-supplemented ovariectomized rats (E2 group). At 12 weeks following left ventricular blood sacrificed to detect plasma estradiol (E2), interleukin-1β (IL-1β) and IL-6 levels. Bone mineral density (BMD) of the lumbar spine was evaluated using dual-energy X-ray absorptiometry, and the left femur proximal 1/3 slices were observed using transmission electron microscopy. Uterine wet weight and the uterus index (ratio of uterine wet weight and body weight) were compared, and the uterine endometrium was observed using a light microscope. In the OVX group, serum E2 was significantly lower and IL-1β and IL-6 levels were significantly higher compared with the sham group. By contrast, serum E2 levels increased and IL-1β levels decreased in the olive group, but showed no significant difference compared with the sham group. The lumbar spine BMD in the olive group was increased compared with OVX group. Electron microscopy revealed sparse collagen fibers in the OVX group, with decreased density and multi-cavity, showing pathological features of osteoporosis. By contrast, the situation was improved in the E2 and olive groups, in which organelles such as the rough endoplasmic reticulum, mitochondria and Golgi apparatus were visible and active. Compared with the sham group rats, the uterine wet weight and uterine index decreased in the OVX and olive groups; however, no statistically significant difference was observed in the E2 group. Furthermore, endometrial hyperplasia was not observed in the olive group, which were apparently different from E2 group. The present results suggest that olive oil can effectively reduce bone loss in ovariectomized rats, and with no or only mild effects on the uterine endothelium.

Effect of Hesperidin With and Without a Calcium (Calcilock) Supplement on Bone Health in Postmenopausal Women.

Citrus fruits contain unique flavanones. One of the most abundant of the flavanones, hesperidin, has been shown to prevent bone loss in ovariectomized rats. The objective of the study was to measure the effect of hesperidin with or without calcium supplementation on bone calcium retention in postmenopausal women. The study was a double-blind, placebo-controlled, randomized-order crossover design of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Bone calcium retention was determined from urinary excretion of the rare isotope, (41)Ca, from bone. Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (P < .04). Calcium supplementation (Calcilock), in combination with hesperidin, is effective at preserving bone in postmenopausal women.

Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin.

IntroductionOsteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. Single use of aspirin or adipose-derived stromal cells (ASCs) has been recognized recently to be effective against osteoporosis. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. The underlying mechanisms were investigated in vitro and in vivo.MethodsFirstly, allogeneic rASCs were isolated and cultured, and the conditioned medium (CM) from the maintenance of rASCs was collected. Secondly, the OVX rats were administrated CM, rASCs, aspirin (ASP) or rASCs + ASP, respectively. Twelve weeks later, the anti-inflammatory and osteogenic effects were assessed by micro-CT, undecalcified histological sections, dynamic histomorphometric analyses and serologic assays for biochemical markers. Finally, a Transwell migration assay in vitro and cell-trafficking analyses in vivo were used to explore the effects of aspirin on rASC migration.ResultsSystemic administration of aspirin and rASCs attenuated OVX-induced bone loss better than single use of aspirin or ASCs (p < 0.05, respectively). Next, we analyzed the underlying mechanisms of the anti-inflammatory and chemotactic abilities of aspirin. Aspirin suppressed serum levels of the pro-inflammatory cytokines on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and the anti-inflammatory ability was positively associated with bone morphometry. Also, aspirin exhibited excellent chemotactic effects in vitro and accelerated the homing of allogeneic rASCs into bone marrow during early in vivo stages.ConclusionsCo-administered aspirin and allogeneic ASCs can partially reverse OVX-induced bone loss in rats. This effect appears to be mediated by the anti-inflammatory and chemotactic abilities of aspirin.

Positive skeletal effect of two ingredients of Psoralea corylifolia L. on estrogen deficiency-induced osteoporosis and the possible mechanisms of action

Estrogen replacement therapy (ERT) is utilized as a major regime for treatment of postmenopausal osteoporosis at present. However, long-term supplement of estrogen may cause uterine hyperplasia and hypertension leading to a high risk of endometrial cancer and breast cancer. Psoralea corylifolia L. has long been used as tonic and food additives in many countries. Previous studies had found two ingredients in P. corylifolia L.: bavachin and bakuchiol exhibited osteoblastic activity. The present study was designed to investigate the protective effect of bakuchiol and bavachin on ovariectomy-induced bone loss and explore the possible mechanism. In vivo, bakuchiol and bavachin could prevented estrogen deficiency-induced bone loss in ovariectomized rats without uterotrophic activity. In vitro studies suggested that bakuchiol and bavachin induced primary human osteoblast differentiation by up-regulating the Wnt signalling pathway. This study suggests that such a bone-protective role makes them a promising and safe estrogen supplement for the ERT.

Enhancement of osteogenesis post-splenectomy does not attenuate bone loss in ovariectomized rats.

The roles of different immune cell populations and cytokines in bone metabolism have been extensively investigated. However, the influence of whole immune organ removal on osteopathology remains unknown. In the current study, we investigated the effects of splenectomy on bone metabolism and microarchitecture in rats with or without concurrent ovariectomy. Ovariectomized (OVX) rats were used as osteoporosis model. Sixty 12-week-old female rats were randomized into 4 groups (n = 15): sham, splenectomized (SP), ovariectomized, as well as ovariectomized and splenectomized (OVX + SP). Bone microarchitecture was assessed by micro CT analysis at 4 week and 12 week post-operation, respectively. Bone pathology and metabolism were evaluated via immunohistochemical staining. The serum levels of alkaline phosphatase (ALP), tumor necrosis factor-alpha (TNF-α), tartrate-resistant acid phosphatase 5b (Tracp5b), and C-terminal telopeptide (CTx) were analyzed at 4 and 12 weeks post-operation. Removal of the spleen led to alterations in the homeostasis of bone metabolism and increased bone formation in rats. In this study, our findings indicate that the spleen is involved in skeletal metabolism.

Black rice (Oryza sativa L.) extracts induce osteoblast differentiation and protect against bone loss in ovariectomized rats.

Osteoporosis, an age associated skeletal disease, exhibits increased adipogenesis at the expense of osteogenesis from common osteoporotic bone marrow cells. In this study, black rice (Oryza sativa L.) extracts (BRE) were identified as osteogenic inducers. BRE stimulated the alkaline phosphatase (ALP) activity in both C3H10T1/2 and primary bone marrow cells. Similarly, BRE increased mRNA expression of ALP and osterix. Oral administration of BRE in OVX rats prevented decreases in bone density and strength. By contrast, BRE inhibited adipocyte differentiation of mesenchymal C3H10T1/2 cells and prevented increases in body weight and fat mass in high fat diet fed obese mice, further suggesting the dual effects of BRE on anti-adipogenesis and pro-osteogenesis. UPLC analysis identified cyanidin-3-O-glucoside and peonidin-3-O-glucoside as main anti-adipogenic effectors but not for pro-osteogenic induction. In mechanism studies, BRE selectively stimulated Wnt-driven luciferase activities. BRE treatment also induced Wnt-specific target genes such as Axin2, WISP2, and Cyclin D1. Taken together, these data suggest that BRE is a potentially useful ingredient to protect against age related osteoporosis and diet induced obesity.

Voluntary wheel running mitigates the stress-induced bone loss in ovariectomized rats.

In estrogen-deficient rodents with osteopenia, repetitive exposure to mild-to-moderate stress, which mimics the chronic aversive stimuli (CAS) of the modern urban lifestyle in postmenopausal women, has been hypothesized to cause the bone microstructure to further deteriorate. Recently, we have provided evidence in rats that voluntary impact exercise, e.g., wheel running, is as effective as pharmacological treatments for stress-induced anxiety and depression. The present study, therefore, aims to investigate whether a 4-week CAS exposure aggravates trabecular bone loss in ovariectomized (Ovx) rats, and whether CAS-induced bone loss can be rescued by voluntary wheel running. CAS was found to elevate the serum levels of corticosterone, a stress hormone from the adrenal gland. Dual energy X-ray absorptiometry revealed a decrease in bone mineral content (BMC) in the tibiae of CAS-exposed Ovx rats as compared to the CAS-free Ovx rats (control), while having no detectable effect on bone mineral density (BMD). Bone histomorphometric analysis of the proximal tibial metaphysis showed that CAS decreased trabecular bone volume and increased trabecular separation, which were completely restored to the baseline values of Ovx rats by voluntary wheel running. This CAS-induced trabecular bone loss in Ovx rats was probably due to an enhancement of osteoclast-mediated bone resorption, as indicated by increases in osteoclast surface and active erosion surface. Moreover, wheel running as well as non-impact exercise (endurance swimming) effectively increased the tibial BMD and BMC of CAS-exposed Ovx rats. It can be concluded that exercise is an effective intervention in mitigating CAS-induced bone loss in estrogen-deficient rats.

The protective effect of lycopene intake on bone loss in ovariectomized rats.

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 200ppm. The tibial bone mineral density (BMD) in the 50, 100, and 200ppm groups was significantly higher than that in the 0ppm group. Serum and urinary bone resorption marker levels were significantly lower in the 50, 100, and 200ppm groups than in the 0ppm 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.

The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats.

[Purpose]Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats.[Methods]Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitamin D3 and nicotine (VDN) (control rats [Con], n = 7), which is an animal model for endothelial dysfunction and bone loss; voluntary climbing resistance exercise with OVX plus VDN (climbing rats [Clim], n = 6), and swimming exercise with OVX plus VDN (swimming rats [Swim], n = 7). The period of exercise training was 8 weeks.[Results]The endothelin-1 (ET-1) protein levels were significantly lower in the Clim and Swim groups than in the Con. The endothelial nitric oxide synthase protein levels were significantly higher in the Swim group than in the Con, but they did not differ between the Clim and Con groups. The cortical bone mineral density in the tibia and breaking energy of the femur were significantly higher in the Clim group than in the Con, but this positive effect was not seen in the Swim group.[Conclusion]Voluntary climbing exercise decreased arterial ET-1 protein levels and prevented bone loss in a postmenopause-model rat combining OVX and VDN. Conversely, swimming suppressed endothelial dysfunction of the arteries but did not prevent bone loss. Thus, the type of exercise should be cautiously chosen for enhancing vascular function and bone status, especially in females after menopause.

Eldecalcitol improves endothelial function in the femoral artery and prevents bone loss in ovariectomized rats

Eldecalcitol improves endothelial function in the femoral artery and prevents bone loss in ovariectomized rats

Comparing the disease modifying effects of alendronate to risedronate in the rat anterior cruciate ligament transection model of osteoarthritis

Comparing the disease modifying effects of alendronate to risedronate in the rat anterior cruciate ligament transection model of osteoarthritis