OBJECTIVESTo investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency.

METHODSIn this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.

RESULTSThe mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3.

CONCLUSIONSThe CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

Cytokines ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; Humans ; Janus Kinases ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; RNA, Messenger ; genetics ; metabolism ; STAT Transcription Factors ; metabolism ; Signal Transduction ; Up-Regulation ; Yin Deficiency ; drug therapy ; genetics

Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing'e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (β-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of β-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.
Biomarkers ; blood ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Calcium, Dietary ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Hydroxycholecalciferols ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; blood ; drug therapy ; Proteins ; drug effects ; metabolism ; Random Allocation ; Vitamin D ; analogs & derivatives ; blood

OBJECTIVETo observe the effect of total flavones of Epimedium leptorrhizum (YYH-C) on osteoporosis in ovariectomized rats.

METHODOvariectomized female rats were randomly divided into the model group, YYH-C lower, middle and high dose (0.7, 1.4, 2.8 g x kg(-1)) groups, the positive drug Bujiale (0.15 mg x kg(-1)) group, and the sham group. The rats were orally ad-ministrated with drugs for three months. Parathyroid hormone (PTH), procollagen I N-terminal peptide (PINP), alkaline phosphatase (ALP), calcium (Ca) and phosphrous (P) in serum were detected. Femur bones and vertebrae bones of left side were collected to determined bone metrological indexes, including bone mineral density (BMD), bone Ca, and bone ash weight/dry weight percentage. Femur bones of right side were collected to for a morphological observation of bone.

RESULTCompared with the sham group, the model group showed significantly higher PTH and ALP content but obviously lower PINP and Ca content. The three YYH-C 3 groups could resist the decrease of PINP. Specifically, low and middle dose groups could remarkably inhibit the increase of PTH, and the high dose group could increase the Ca content in serum, but without significant effect on the rise in ALP. There was no significant difference in P content in serum in each group. BMD, ash weight/dry weight percentage, Ca and P content of the model group were significantly lower than those in the sham group. The high dose YYH-C group could significantly increase BMD. All of the three YYH-C groups could notably increase ash weight/dry weight percentage and Ca, P content in femur bones and vertebrae bones. YYH-C could significantly increase average thickness, area, area percentage of bony trabeculae, cortical bone area percentage of femoral shaft and the number of osteoblasts on the surface of bony trabeculae, and decrease the number of osteoclasts.

CONCLUSIONYYH-C can effectively control the bone mass loss of rats with ovariectomy-induced osteoporosis, prevent the changes in bone microstructure, and inhibit bone absorption, so as to resist high turn-over osteoporosis after ovariectomy. [Key words] total flavones of Epimedium leptorrhizum; ovariectomized rat; osteoporosis

Alkaline Phosphatase ; metabolism ; Animals ; Bone Density ; drug effects ; Calcium ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Epimedium ; chemistry ; Female ; Flavones ; administration & dosage ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; metabolism ; physiopathology ; Ovariectomy ; Parathyroid Hormone ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of eight specifications of Cervi Cornu Pantotrichum on the osteoporosis of ovariectomized rats and grade the eight different specifications of Cervi Cornu Pantotrichum.

METHODTotally 100 SD female rats were divided randomly into 10 groups, namely the normal group, the model group and eight Cervi Cornu Pantotrichum groups of different specifications. Their bilateral ovaries were excised to reproduce the osteoporosis model. Meanwhile, the rats were given the eight different specifications of Cervi Cornu Pantotrichum for consecutively 12 weeks. Subsequently, the effects of the different specifications of Cervi Cornu Pantotrichum on bone mineral density and serum biochemical indicators of rats were observed. A clustering analysis was made for the eight specifications of Cervi Cornu Pantotrichum, with the serum content of ALP, BMP-2 and BGP as influencing factors.

RESULTAfter 12 weeks, the eight different specifications of Cervi Cornu Pantotrichum could significantly improve ALP, BMP-2, BGP in serum and bone mineral density of ovariectomized rats. And the cluster analysis showed similar results to the quality classification of traditional commercial herbs Cervi Cornu Pantotrichum.

CONCLUSIONDifferent specifications of Cervi Cornu Pantotrichum can antagonize the osteoporosis of ovariectomized rats, and their effects are related to the quality of commercial herbs.

Animals ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Deer ; Disease Models, Animal ; Female ; Horns ; chemistry ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; metabolism ; physiopathology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia.

METHODSTotally 38 patients of postmenopausal women with breast cancer, who received aromatase inhibitors (AIs), were assigned to the treatment group (21 cases) and the control group (17 cases) by using random digit table. All patients took Caltrate D Tablet (containing Ca 600 mg and Vit D3 125 IU), one tablet daily. Patients in the treatment group took SJR, 6 g each time, twice daily for 6 successive months. The bone mineral density (BMD) level was detected before treatment and at months 6 after treatment. Levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type II collagen (CTX-II) were detected by enzyme linked immunosorbent assay (ELISA). The drug safety was also assessed.

RESULTSCompared with before treatment, BMD of L2-4 and femur neck obviously increased in the treatment group at month 6 after treatment (P < 0.01), serum BALP and TRAP decreased (P < 0.05). Compared with before treatment, BMD of L2-4 and femur neck obviously decreased in the control group at month 6 after treatment (P < 0.05), serum BALP and TRAP increased (P < 0.01). Compared with the control group, lumbar and femur neck BMD obviously increased, serum levels of BGP and BALP obviously decreased, and serum levels of CTX-II and TRAP obviously increased in the treatment group at month 6 after treatment (P < 0.01). No serious adverse event occurred during the treatment period. Bone fracture occurred in one case of the control group (5.8%).

CONCLUSIONSJR could attenuate bone loss of postmenopausal women with breast cancer who received AIs, increase BMD and improve abnormal bone metabolism.

Acid Phosphatase ; blood ; Aged ; Alkaline Phosphatase ; blood ; Aromatase Inhibitors ; adverse effects ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; Collagen Type II ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Isoenzymes ; blood ; Middle Aged ; Osteocalcin ; blood ; Osteoporosis, Postmenopausal ; chemically induced ; prevention & control ; Peptide Fragments ; blood ; Tartrate-Resistant Acid Phosphatase

OBJECTIVETo observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism.

METHODSTotally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-β in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-β mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-β mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05).

CONCLUSIONSThere was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estrogens ; deficiency ; metabolism ; Female ; Flow Cytometry ; Humans ; Interleukin-17 ; Mice ; Mice, Inbred BALB C ; Osteoporosis, Postmenopausal ; drug therapy ; RNA, Messenger ; Spleen ; T-Lymphocyte Subsets ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transforming Growth Factor beta ; metabolism

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

Postmenopausal osteoporosis is one of the commonest systemic bone metabolism diseases among menopausal women, mainly caused by lowering internal estrogen. Although Hormone Replacement Therapy (HRT) is an effective method in clinical practice for years, it shows side-effect in increasing gynecological carcinoma. It has already been proved by clinical tests that multiple traditional Chinese medicine formulas and their monomer ingredients and phytoestrogen-like active constituents contained in traditional Chinese medicines are effective on treating osteoporosis with relatively less side-effects comparing with HRT. They show protective and therapeutic effects by acting on estrogen receptors of targeted tissues and targeted cells and then affecting expressions of bone metabolism-related regulatory proteins and factors in downstream signal conduct paths. Recent studies on estrogen related receptor (ERR) provide new possibilities and pathways for mechanism of traditional Chinese medicine and their active constituents in osteoporosis.
Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Osteoporosis, Postmenopausal ; drug therapy ; Receptors, Estrogen ; metabolism

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

OBJECTIVETo compare therapeutic effects of warm needle moxibustion and medication on osteoporosis and to study the mechanism.

METHODSForty cases were randomly divided into an acupuncture group and a medication group, 20 cases in each group. The acupuncture group was treated by warm needle moxibustion at Dazhu (BL 11), Ganshu (BL 18), Shenshu (BL 23), Zusanli (ST 36), Yanglingquan (GB 34) etc. once other day, for 3 months; and the medication group was treated by oral administration of tablet Caltrate with Vit D2 for 3 months. The changes of bone mass density (BMD), estradiol (E2), osteocalcin (bone growth protein, BGP), urine calcium/creatinine (Ca/Cr) in the two groups before and after treatment and therapeutic effects were investigated.

RESULTSAfter treatment, BMD significantly increased (P<0.05, P<0.01) in the acupuncture group and did not signifi cantly changed in the medication group (P>0.05) with a significant difference between the two groups (P<0.05). After treatment E2 level significantly increased as compared with before treatment in both of groups (P<0.01); after treatment BGP significantly decreased as compared with before treatment in both of groups (P<0.01); after treatment Ca/Cr significantly decreased as compared with before treatment in the acupuncture group (P<0.05) ; af ter treatment, there were significant differences in BGP and Ca/Cr between the two groups (P<0.05 or P<0.01). The clinically controlled rate in the acupuncture group and in the medication group were 35.0%, 5.0%, respectively, the therapeutic effect of the acupuncture group being better than that of the medication group (P<0.01).

CONCLUSIONThe therapeutic effect of warm needle moxibustion on osteoporosis is better than that of oral administration of tablet Caltrate with Vit D2 and it can increase levels of hormones and delay bone loss. It is an effective method for preventing and treating postmenopausal osteoporosis.

Acupuncture Points ; Aged ; Bone Density ; Bone and Bones ; metabolism ; physiopathology ; Calcium ; urine ; Creatinine ; urine ; Estradiol ; metabolism ; Female ; Humans ; Middle Aged ; Moxibustion ; Osteocalcin ; metabolism ; Osteoporosis, Postmenopausal ; drug therapy ; metabolism ; physiopathology ; therapy