OBJECTIVE: To explore compounds, targets and mechanism of METHODS: The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data. RESULTS: Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A. CONCLUSION The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.
Drugs, Chinese Herbal ; Female ; Humans ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy* ; Osteoporosis, Postmenopausal

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.
Humans ; Female ; Osteoporotic Fractures ; Osteoporosis, Postmenopausal/drug therapy* ; Postmenopause ; Osteoporosis ; Bone Density ; Estrogens ; Iron/therapeutic use*

To propose the new concept of multidimensional omics, and define that the multidimensional omics is a proper method for studying the material base and mechanism of traditional Chinese medicine (TCM) compounds. Zhuanggu Zhitong capsule was taken for example to study its effect against experimental postmenopausal osteoporosis. From the perspective of chemi-omics, genomics and proteomics of TCM, it systematically interpreted the efficacious materials and mechanisms of Zhuanggu Zhitong capsule in preventing and treating experimental postmenopausal osteoporosis, while taking the lead in designing a three dimensional form to intuitively exhibit the results of the multidimensional omics study. This study provides a new idea and solution for studies on the efficacious materials and mechanisms of TCM compounds.
Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Female ; Gene Expression ; drug effects ; Genomics ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; metabolism ; Proteomics

OBJECTIVETo observe the effect of Chinese herbal medicine Qianggu drink ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in ovariectomized rats and to explore its mechanism.

METHODSSixty female SD rats (weight 230 to 280 gram) were randomized into three groups: Qianggu drink ([Chinese characters: see text]) group (treatment group), Miacalcic group (control group) and blank group. The osteoporosis model was established successfully after all rats were ovariectomized for 10 weeks. The treatment group was used intragastric infusion with Qianggu drink ([Chinese characters: see text]) 0.001 ml/kg once a day. The control group was used hypodermic injection once a day with Miacalcic 0.72 U/kg. Five rats were killed respectively and the lumbar specimens were taken and cut for bone histomorphometric analysis at 45, 90, 135 and 180 days after the treatment.

RESULTSThe thickness of trabecular bone in treatment group had the statistical significance with control group at 135 days after ovariectomized rats were given the medicine. The data of BV/TV and the thickness and space of trabecular bone had statistical significance compared with control group and blank group 180 days later.

CONCLUSIONQianggu drink ([Chinese characters: see text]) could effectively improve the histomorphometry indexes. The mechanism probably plays by stimulating osteogenesis and inhibiting the cytoactive of osteoclast and the trend of bone transform.

Animals ; Female ; Humans ; Lumbar Vertebrae ; drug effects ; pathology ; Osteoporosis, Postmenopausal ; drug therapy ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThere are no conclusive studies evaluating the interaction between icariin and exercise for treatment of osteoporosis; the efficacy and safety of this treatment combination remains to be evaluated. The purpose of this study was to investigate the effects of icariin treatment combined with exercise therapy on bone parameters and body weight of ovariectomized rats.

METHODSOvariectomized rats were used as a model of postmenopausal osteoporosis and were exposed to either icariin treatment, exercise, hormone replacement therapy, or a combination of the above. Untreated, ovariectomized rats and sham operated rats were used as controls. After 3 months of experimental interventions the effects of the treatments on the body and uterine weights, the physical and biomechanical properties of bones, and the expression of the osteoblast-specific gene Osterix (Osx), were assessed.

RESULTSThe weight gain of the ovariectomized rats was greater than that of the treated experimental groups. Uterine weight and serum estradiol levels were significantly greater in sham operated and estrogen-treated ovariectomized rats than in the other groups. Biomechanical parameters were improved significantly in ovariectomized rats treated with exercise alone or treated with exercise and icariin. Osx expression was increased in ovariectomized rats treated with exercise and icariin or treated with just icariin.

CONCLUSIONSExercise combined with icariin had a synergistic effect in the early prevention of osteoporosis in ovariectomized rats. The effects of icariin and exercise on osteoporosis are worth further exploration.

Animals ; Female ; Flavonoids ; therapeutic use ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; therapy ; Ovariectomy ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effectiveness of alendronate Chinese national product in the prevention and treatment of postmenopausal osteoporosis.

METHODSThe 56 postmenopausal women with osteopenia or osteoporosis were randomly divided into two groups: treated with alendronate 10 mg/d (28 cases) orally and placebo (28 cases), for 6 months. All subjects received 600 mg/d of calcium carbonate and vitamin D 1,000 U/d. Bone mineral density (BMD) of the lumbar spine, femoral neck, trochanter and Ward's triangle were measured by dual energy X-ray absorptiometry as well as the markers of bone turnover were analysed at the beginning and the end of the study.

RESULTSThe results showed that lumbar spine BMD increased by 5% in the alendronate group (P < 0.01), but decreased in BMD of the lumbar spine and femur in the placebo group (P < 0.05) after 6 months of treatment. In the alendronate group the marker of bone resorption and bone formation were significantly decreased after alendronate therapy. There were no change in placebo group.

CONCLUSIONSAlendronate (Chinese national product) is effective in reducing bone turnover and promoting bone mass of postmenopausal osteoporosis.

Absorptiometry, Photon ; Aged ; Alendronate ; therapeutic use ; Bone Density ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; prevention & control

The present study was designed to determine if levels of serum cytokines, such as interleukin (IL) -1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are different in osteoporotic and non-osteoporotic postmenopausal women, and to evaluate the effects of calcitonin and alendronate therapies over a six month period on serum cytokine levels in postmenopausal osteoporotic women. Serum levels of IL-2, TNF-alpha and IL-8 were found to be significantly higher (p < 0.05), and serum IL-10, and IL-6r significantly lower in the calcitonin (N=60) and the alendronate (N=60) treatment groups than in the control group (N=50) (p < 0.05). But, no significant difference was apparent between the calcitonin and alendronate treated groups before treatment. Statistically significant changes occurred in patients, with respect to the levels of serum IL-6r, and IL-8 after one month (p < 0.05), in IL-2r, IL-6r, IL-8, IL-10 after three months, and in IL-1beta, IL-6r, IL-8, IL-10 and TNF-alpha after six months of calcitonin therapy (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-8 and IL-10 after three months, and in TNF-alpha after six months in the calcitonin treated group and in the control group, whereas these parameters were significantly different at baseline. In the alendronate treated group, statistically significant changes occurred in the levels of serum IL-1alpha and IL-6 after three months, and in IL-1beta, IL-6, IL-6r and TNF-alpha after six months (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-10 after three months or in TNF-alpha after six months between the alendronate treatment group and the control group, whereas these parameters were significantly different at baseline. In conclusion, we suggest that; 1) not only IL-1, IL-6, TNF-alpha and IL-11 but also IL-2, IL-8 and IL-10 may have roles in the etiopathogenesis of osteoporosis, 2) calcitonin therapy have a more distinct influence on serum levels of some cytokines and have an earlier effect than alendronate therapy (especially upon IL-2r, IL-8, and IL-10). Nevertheless, further longitudinal studies are needed to identify the cytokines involved in the pathogenesis of postmenopausal osteoporosis and to evaluate the influence of different treatments on these cytokines.
Aged ; Alendronate/*therapeutic use ; Calcitonin/*therapeutic use ; Cytokines/*metabolism ; Female ; Human ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy/*metabolism ; Time Factors

This study evaluated the outcome indicators of the randomized controlled trials(RCTs) of traditional Chinese medicine(TCM) in the treatment of postmenopausal osteoporosis(PMOP) to provide a reference for the related research. Four Chinese databa-ses(CNKI, VIP, Wanfang and CBM) and three English databases(Cochrane Library, EMbase and PubMed) were searched syste-matically to screen RCTs of TCM in the treatment of PMOP according to the pre-set criteria, and the quality of the included trials was evaluated by the Cochrane risk-of-bias tool. A total of 29 627 articles were initially retrieved, and finally, 43 articles were included, including 34 in Chinese and 9 in English. As revealed by the results, the outcome indicators of 43 RCTs were mainly divided into six categories, with biochemical indicators accounting for 54.59%, bone mineral density(BMD) for 26.57%, quality of life for 6.28%, fracture for 1.94%, safety for 5.31%(including adverse reactions or events) and others for 5.31%. Biochemical indicators showed the maximum occurrence, followed by BMD. Many problems were found in the selection of outcome indicators of the TCM RCTs in the treatment of PMOP, such as the confusion of primary and secondary outcome indicators, the lack of endpoint criteria and vital clinical outcome indicators substituted by intermediate indicators, inconsistent evaluation standard of syndrome curative efficacy and neglected blinding in the measurement of subjective outcome indicators. The problems also included importance given to the efficacy indicators instead of the adverse outcome indicators, unnormalized indicator name, large quantitative range of the indicators, unconventional application of TCM efficacy criteria, seldom used confidence interval, relative effect indicator and absolute effect indicator.
Bone Density ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Medicine, Chinese Traditional ; Osteoporosis, Postmenopausal/drug therapy* ; Quality of Life ; Treatment Outcome

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D3 (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.
Adult ; Aged ; Alendronate/adverse effects/*therapeutic use ; Cholecalciferol/adverse effects/deficiency/*therapeutic use ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy ; Vitamin D Deficiency/*drug therapy

OBJECTIVETo observe the clinical effect of acupuncture combined with TDP for treatment of postmenopausal patients with deficiency of liver and kidney syndrome and to explore its mechanism.

METHODSOne hundred and twelve cases were randomly divided into an acupuncture group and a medication group, 56 cases in each group. The acupuncture group was treated with acupuncture combined with TDP, Shenshu (BL 23), Mingmen (GV 4) and Guanyuan (CV 4) were selected as main points; the medication group was treated with oral administration of Nylestriol and Oryzanol. The therapeutic effects were evaluated after treatment of 3 months in the two groups, and the changes of estrogen,bone mineral density and endometrium of patients were observed before and after treatment.

RESULTSThe total effective rate of 94.6% in acupuncture group was superior to 75.0% in medication group (P<0.01), the acupuncture group was better than the medication group in increasing bone mineral density and decreasing the endometrial thickness (P<0.05, P<0.01), the medication group was better than the acupuncture group in decreasing the levels of serum follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increasing the estradiol (E2) level (all P<0.01).

CONCLUSIONThe clinical effect of acupuncture combined with TDP for treatment of postmenopausal patients with deficiency of liver and kidney syndrome is significant, and it can increase bone mineral density, decrease endometrial thickness and obviously regulate the estrogen level.

Acupuncture Therapy ; Bone and Bones ; metabolism ; Estrogens ; metabolism ; Female ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Middle Aged ; Osteoporosis, Postmenopausal ; metabolism ; physiopathology ; therapy