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Clinical Study Of Related Factors Of Wnt/β-catenin Signaling Pathway And Bone Metabolism And Therapeutic Effect Of Qine’E Pill In Postmenopausal Osteoporosis

Posted on:2014-02-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:X J XuFull Text:PDF
GTID:1224330398985738Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Part one Serum β-catenin levels associated with the ratio of RANKL/OPG in patients with postmenopausal osteoporosisObjective:To demonstrate the role of Wnt/p-catenin canonical pathway in postmenopausal osteoporosis by evaluating serum β-catenin levels in patients with postmenopausal osteoporosis and analyzing their possible relationship with serum osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), the ratio of RANKL/OPG, sclerostin (SOST), and bone turnover markers.Methods:480patients with postmenopausal osteoporosis and170healthy postmenopausal women were enrolled in the study. Serum β-catenin, OPG, RANKL, and sclerostin levels were measured by enzyme-linked immunosorbent assay. Bone status was assessed by measuring bone mineral density and bone turnover markers. Estradiol levels were also detected.Results:Serum P-catenin levels were lower in postmenopausal osteoporotic women compared to non-osteoporotic postmenopausal women (26.26±14.81vs39.33±5.47pg/ml, P<0.001). Serum P-catenin was positively correlated with osteoprotegerin (r=0.232, P<0.001) and negatively correlated with the ratio of RANKL/OPG, body mass index, and sclerostin (r=-0.128, P=0.005; r=-0.117, P=0.010; r=-0.400, P<0.001; respectively) in patients with postmenopausal osteoporosis. No correlation of P-catenin with age, height, weight, estradiol, RANKL, and bone turnover markers was observed in postmenapausal osteoporosis. In healthy postmenopausal women, there was no association between β-catenin and other parameters.Conclusion:The results indicate that lower serum P-catenin may be involved in the pathogenesis of postmenopausal osteoporosis. Functional communication between RANKL/RANK/OPG system and Wnt pathways plays an important role in postmenopausal osteoporosis. Part two Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosisObjective:To gain insight into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin levels in postmenopausal women and investigated its possible associations with bone turnover markers, including p-isomerized C-terminal crosslinking of type I collagen (β-CTX), intact N-terminal propeptide of type I collagen (PINP), N-mid fragment of osteocalcin (N-MID-OT), and25-hydroxy vitamin D (25(OH)D) in patients with postmenopausal osteoporosis.Methods:We detected serum sclerostin, and measured lumbar spine bone mineral density in650Chinese postmenopausal women. We also assessed serum levels ofβ-CTX, PINP, N-MID-OT,25(OH)D, and estradiol. In addition, we analysed the correlations of serum sclerostin with BMD and bone turnover markers in postmenopausal osteoporosis.Results:Serum sclerostin levels were lower in postmenopausal osteoporotic women compared with non-osteoporotic postmenopausal women (38.79±7.43pmol/L vs52.86±6.69pmol/L, P<0.001). Serum sclerostin was positively correlated with lumbar spinal bone mineral density (r=0.391, P<0.001) and weakly negatively correlated with p-CTX, PINP, N-MID-OT (r=-0.225, P<0.001; r=-0.091, P=0.046; r=-0.108, P=0.018; respectively) in postmenopausal osteoporosis. There was no significant association of serum sclerostin with age, body mass index,25(OH)D, and estradiol (r=-0.004, P=0.926; r=0.067, P=0.143; r=0.063, P=0.165; r=-0.045, P=0.324; respectively).Conclusion:The results indicate that sclerostin may be involved in the pathogenesis of postmenopausal osteoporosis and plays a role in bone turnover. Part three The effect of Qing’E pill on BMD and bone turnover markers in patients with postmenopausal osteoporosisObjective:This study aimed to observe the long-term effect of Chinese herbal Qing’E pill on BMD and bone turnover markers in patients with postmenopausal osteoporosis.Methods:60patients with postmenopausal osteoporosis were randomly divided into Qing’E pill treatment group and placebo control group. The patients in both groups received treatment for6months, and a follow-up of1year. The BMD, bone turnover markers, and estrogen levels were detected in each patient at baseline, after6months of treatment, after1year of medication discontinuation respectively.Results:There was no significantly increased bone mineral density in either observation period, whereas P-CTX, a bone resorption marker was decreased after6months in Qing’E treatment group (P<0.01). However, BMD levels were significantly decreased at both the observation periods in control group. There was no significant difference in bone turnover markers compared with them in the baseline.Conclusion:Qing’E pill has a long-term effect on maintaining BMD, and an effect on inhibiting bone resorption in patients with postmenopausal osteoporosis.
Keywords/Search Tags:β-catein, Postmenopausal osteoporosis, Osteoprotegerin, Receptor, activator of nuclear factor kappa B ligand, Bone turnover markers, Bone mineraldensitySclerostin, Bonemineral densityQing’E pill, Bone mineral density, Boneturnover markers
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