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

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 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

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 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 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

Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and risedronate, is widely used in the treatment with osteoporosis in Japan. Etidronate increases the lumbar bone mineral density (BMD), and prevents new vertebral fractures, in patients with osteoporosis, while alendronate and risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2, should be initially chosen for the treatment of osteoporosis, because they are more efficacious than vitamin K2. Available evidence suggest that risedronate prevents deterioration of the connectivity of the trabeculae in ovariectomized rats, whereas vitamin K2 increase the trabecular thickness, and that a combination of risedronate and vitamin K2 has a synergistic effect on preventing the deterioration of trabecular bone architecture induced by estrogen deficiency. Some studies have shown that combined treatment with etidronate and vitamin K2 appears to be more effective than etidronate alone in the prevention of new osteoporotic vertebral fractures. Based on these findings, combined treatment with vitamin K2 and bisphosphonates may be more efficacious in the prevention new vertebral fractures than a single treatment with bisphosphonate in postmenopausal women with osteoporosis. Thus, this combined treatment should be recommended for the treatment of postmenopausal osteoporosis. It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency.
Aged ; Bone Density/drug effects ; Bone and Bones/drug effects/metabolism ; Diphosphonates/*administration & dosage ; Drug Therapy, Combination ; Female ; Human ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy ; Vitamin K 2/*administration & dosage

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

BACKGROUNDRaloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis.

METHODSThis was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis.

RESULTSAt the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P > 0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P < 0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo.

CONCLUSIONSRaloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Aged ; Aged, 80 and over ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Female ; Humans ; Lipids ; blood ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; Raloxifene Hydrochloride ; adverse effects ; therapeutic use

OBJECTIVETo investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis.

METHODSA total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed.

RESULTSA total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group.

CONCLUSIONThe effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.

Aged ; Biomarkers ; metabolism ; Bone Density ; drug effects ; genetics ; Bone Diseases, Metabolic ; genetics ; metabolism ; Bone Remodeling ; drug effects ; genetics ; Bone and Bones ; drug effects ; Double-Blind Method ; Female ; Humans ; Middle Aged ; Osteoporosis ; drug therapy ; Osteoporosis, Postmenopausal ; drug therapy ; Polymorphism, Genetic ; Postmenopause ; drug effects ; Raloxifene Hydrochloride ; pharmacology ; therapeutic use ; Selective Estrogen Receptor Modulators ; pharmacology ; Women