Narrow Results

Dang-Gui-Ji-Hwang Yeum (DGJHY; an Oriental prescription), has been successfully used for the management of osteoporotic disorders in China, Japan and Korea. In this study, we have characterized the effect of DGJHY on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in sham, OVX and DGJHY-administered OVX rats. Light microscopic analyses showed a porous or an eroded appearance on the tibial trabecular bone surface in OVX rats, whereas those of the sham and DGJHY-administered OVX rats were composed of fine particles. The trabecular bone area and the trabecular thickness in OVX rats were significantly lower than those of sham rats. Moreover, these reductions in OVX rats were significantly reversed by the administration of DGJHY for 7 weeks, and osteoclast numbers were also significantly reduced. Although no differences were observed between OVX and DGJHY-administered OVX rats and the sham animals at the T₃ level, we have found significant differences between these two groups at the T₄ level. However, serum phosphorus, calcium, mechanical strength and the surface appearance of osteoblasts in the DGJHY-administered OVX rats were similar to those of OVX rats. These results suggest that DGJHY is effective at preventing bone loss in OVX rats.

This study was designed to (1) test the preventive and therapeutic effects of acupuncture on osteopenia in ovariectomized (OVX) rats, and (2) assess whether treatment of different acupuncture points causes different effects on tibiae, femora or lumbar spines. Thirty-five female Sprague-Dawley rats were divided into four groups: Sham (sham-operated, non-acupuncture); Model (OVX, non-acupuncture); Acp-A [OVX, bilateral needling of points Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6)]; and Acp-B (OVX, bilateral needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23)). Operations were performed at 8 weeks of age, 1 week later the study was started and continued for 16 weeks. Ovariectomy resulted in decreased bone mineral density (BMD) compared to the sham group over time, and Acp-A tended to have higher BMD than the other OVX groups, especially for tibiae. In addition, the bone ash weight of the Acp groups tended to be heavier than the model group. Deoxypyridinoline, the urinary marker of bone resorption, also appeared to be decreased in both acupuncture groups. Similarly, microarchitecture and bone morphometry of lumbar vertebrae and tibiae, such as bone volume, trabecular thickness, trabecular number, mineralizing surface, bone formation rate, mineral apposition rate, number of nodes and number of node-terminus struts, also showed the same improvement in the acupuncture groups as compared to the model control group. Our findings showed that acupuncture may prevent the development of osteopenia in rats induced by ovariectomy. Needling of Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6) seems more effective than needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23) in bone anabolic regulation.

In order to examine the effects of Kami-kihi-to (KKT or Jia-Wei-Gui-Pi-Tang) on osteopenia, we measured bone mineral density using computed X-ray absorptometry and monitored metabolism and bone tissue in an ovariectomized (OVX) rat model.

Bone mineral density was significantly lower in the OVX group than in normal group 3 months after ovariectomy. However, the bone mineral density of the OVX group administered KKT was clearly higher than that of the untreated OVX group.

Locomotor activity was regular in the normal group and in the OVX groups before administration of KKT. After 6-month administration of KKT, in OVX groups, the pattern of locomotor activity became diphasic with clear active and resting phases, as was also observed in the normal group. The locomotor activity did not decrease in the OVX groups after administration of KKT. At 6 months, the continuity of the trabecular bone was higher in the OVX group administered KKT than in the untreated OVX group. These results indicate that KKT improved the menopausal symptoms and increased the locomotor activity of the OVX group, thereby increasing bone mineral density.

The effects of Korean Safflower (Carthamus tinctorius L) seed oil (SSO) on osteoporosis induced-ovariectomized rats were investigated. A total of 90 female Sprague-Dawley rats, 4-month-old, weighing 200–230 g were randomly assigned into 3 groups (30 animals/group). The animals in group I were sham operated and those of group II and III were ovariectomized (Ovx). After eight weeks, the animals of group I and II received solvent vehicle daily, whereas those of group III were administered SSO orally (1 ml/kg) daily for 30 days. The changes in the serum levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein-3 (IGBP-3), estrogen, total alkaline phosphatase (TALP), bone-specific alkaline phosphatase (BALP), calcium and phosphorous in serum, and also the histomorphology of the proximal tibia metaphysis and femur/body weight (F/B) ratio were examined in all the groups at every 10 days interval. Thirty days later, IGF-I, IGF-II, IGBP-3 and BALP levels were significantly increased (p < 0.05) in group III as compared to groups I and II. There were no significant differences in serum levels of estrogen, TALP and F/B ratio between groups II and III, but estrogen levels were higher in group I. These results suggest that the safflower seeds have possible roles in the improvement of osteoporosis induced-ovariectomized rats.

We investigated whether treatments with beta-blockers or other administrations that have similar actions to β-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels (p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis.

This study examined the estrogenic activity produced by aqueous extracts of silkworm (Bombyx mori) pupae in ovariectomized (OVX) rats. The components of silkworm pupae were extracted in distilled water at room temperature for 6 hours. The ovaries of six-week old female rats were then bilaterally removed. One week after OVX, the animals were treated with 200, 400 or 600 mg/kg/day of silkworm pupae extracts. The body weights of the OVX rats increased remarkably compared to the control rats, however their relative uterus weights to body weights decreased significantly. Treatment with the aqueous extracts of silkworm pupae dramatically improved the decreased uterus weights of OVX rats, with the highest increase observed in treatment with 200 mg/kg/day of the aqueous extracts. Additionally, treatment with aqueous extracts (200 mg/kg/day) of silkworm pupae significantly elevated the serum 17β-estradiol contents of OVX rats when compared to the control animals. To examine the toxic effects of silkworm pupae on the hepatic functions of OVX rats, the levels of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were measured. The serum GOT and GPT levels did not change in response to the administration of aqueous extracts (200, 400 and 600 mg/kg/day) for 4-weeks. Taken together, these results suggest that the aqueous extracts of silkworm pupae may have estrogenic activity, which suggests that silkworm pupae may be useful in the prevention and/or treatment of menopausal disorders caused by deficiencies in female sexual hormones, including estrogen.

Post-menopause, there is an increase in body weight, visceral adiposity, and risk of developing non-alcoholic fatty liver disease (NAFLD), which leads to various cardiovascular diseases (CVDs). Some natural products have proven useful for counteracting the detrimental effects of menopause. The rhizome of Ligusticum chuanxiong Hort. (LC) is a well-known medicinal herb widely used in Chinese communities for the treatment of CVDs. The hepatic and vascular protective effects of LC ethanolic extract under postmenopausal conditions were investigated on ovariectomized (OVX) rats supplemented with or without LC ethanolic extract (600 mg/kg body weight/day, p.o.) or 17β-estradiol (1 mg/kg body weight/day, p.o.) for 12 weeks. The current findings demonstrated that consumption of LC ethanolic extract could reduce the body weight gain, improve serum lipid profile (lowering low density lipoprotein cholesterol but raising high density lipoprotein cholesterol), combat NAFLD, and protect vascular endothelium in the OVX rats. The beneficial effects of LC may be associated with its antioxidant or vasorelaxant compounds, which enhance the levels of hepatic antioxidant enzymes and up-regulate endothelial nitric oxide synthase mRNA expression, respectively. Taken together, LC may be a promising natural supplement for postmenopausal women to prevent NAFLD and CVDs.

This study design is to evaluate the mid-term changes in bone mineral density (BMD) with combined calcium-restricted and ovariectomized miniature porcine models as a large animal model in osteoporosis. The combined old practice hangs on for almost 30 years. Four 6-month-old (T0) female miniature pigs were enrolled in this study. The pigs were fed a normal diet prior to the ovariectomy at the age of 1 year and 3 months (T1) but switched to a diet with restricted calcium content afterwards. Each of the pigs received dual-energy X-ray absorptiometry (DXA) once before ovariectomy, and once every three months (T2, T3, T4) after the ovariectomy to evaluate the changes in BMD. The body weight of all four subject pigs increased significantly during this study ($p<0.05$). The initial changes in both the BMD levels (T1/T2) were found to be statistically insignificant ($p=0.325$ and $p=0.137$, respectively). However, upon comparison of later BMD changes (T3/T4, T1/T3 and T1/T4), statistically significant elevations were found ($p<0.05$ for all three comparisons). Ovariectomy and calcium-restricted diets are ineffective in achieving an osteoporotic porcine model based on BMD assessments. BMD levels of the subject pigs continued to rise until the point at which body growth had stopped because the ideal pigs for surgical experiments were far from maturity. This finding is not unexpected; after all, the subject pigs are not senile. Without violations of the physiology and Institutional Animal Care and Use Committee (IACUC) regulations, moreover, pigs could be fed by strictly calcium-restricted diets or deprived of soybean component feed. Furthermore, the alternative protocols in osteoporotic porcine model shall perform experiments as soon as possible after ovariectomy. We should take other studies about artificial osteoporotic pigs more into consideration whether it is based on a rational method.

Fixation of osteoporotic fracture is always a challenging procedure in orthopedic surgery. Loosening of fixation implants from osteoporotic bone is not uncommon. A large osteoporotic animal model that resembles human osteoporotic changes is therefore essential in osteoporosis research. It can be used to test for better fixation techniques and biomaterials developed for the enhancement of osteoporotic fractures. However, many factors should be considered in developing osteoporotic animal models; these include the comparability to human skeletal physiology, the risk of zoonotic disease, the ease of handling, as well as the possibility of regional and climatic accommodation of the animals. Among the large animals, goat is the most suitable one to fulfill the requirements in the authors' institution and region. This chapter describes the methodologies developed and adopted for developing an osteoporotic goat model. Ovariectomy (OVX), one of the common methods to induce osteoporosis in animals, is systemically described. The importance of a low-calcium diet for accelerating bone loss in OVX goats is incorporated and discussed. The chapter also illustrates different methods of monitoring the development of osteoporosis as well as the relative results. These include the monitoring of serum estradiol concentration, monitoring of changes in bone mineral density (BMD) using peripheral quantitative computed tomography (pQCT) on iliac crest biopsies and calcanei, analysis of the trabecular microarchitecture of iliac crest biopsies using micro-computed tomography (micro-CT), microradiography of iliac crest biopsies, and biomechanical indentation test on calcanei and humeral heads.