| Objective The pathogenesis of postmenopausal osteoporosis was summarized from the theoretical point of view,and the relationship between matrix Gla protein(MGP) and bone metabolism of PMOP was analysed.Then explore the mechanism of fetuin A-matrix Gla proteincalcium phosphate mineralization complexes(FMC) involved in the pathogenesis of PMOP.Besides,to study the clinical curative effect of traditional Chinese medicine Epimedium capsules in the treatment of postmenopausal osteoporosis patients(kidney yang deficiency syndrome).Methods1.Theoretical research:We summarize the pathogenesis of PMOP through reviewing systematically modern literature and analyse the relationship between abnormal bone mineralization and PMOP to provide the basis for the experimental study. Beside,we summarise the mechiansim and treatment of PMOP in tradional Chinese medicine(TCM).2.Correlation between serum matrix Gla protein and bone metabolism:120 postmenopausal osteoporosis women and 60 healthy ostmeno-pausal women were enrolled. Serum MGP m RNA was determined by fluorescent real-time quantitative polymerase chain reaction(PCR).The serum levels of β-crosslinking telopeptide(β-CTX),Ⅰprocollagen(PINP),estradiol(E2)and parathyroid hormone(PTH)were also determined in both group. BMD was analyzed by dual energy X-ray absorptiometry(DXA).3.Study on the mechanism of Fetuin-A-MGP-Calcium phosphate mineral complex(FMC) to participate in PMOP:23 postmenopausal osteoporosis patients and 23 cases of normal postmenopausal women were enrolled. Take part of their lumbar bone tissue after lumbar surgery. Serum Fetuin-A、MGP、BMP2、RUNX2 was measured using enzyme-linked immunosorbent assay(ELISA). The m RNA and the protein of fetuin A, MGP, BMP2 and Runx2 in lumbar bone tissue was measured by PCR and immunohistochemistry separately.4.Efficacy of traditional Chinese Medicine:90 postmenopausal osteoporosis patients were randomly divided into A group(Placebo control group),B group(Epimedium capsules lower dose group)and C group(Epimedium capsules higher dose group). All the patients in three groups received treatment for 24 weeks. Before and after the treatment for 24 weeks, serum Fetuin-A and MGP was measured using enzyme-linked immunosorbent assay(ELISA).The serum levels of β-CTX、P1NP were measured by electrochemiluminescence ECL.BMD was analyzed by dual energy X-ray absorptiometry(DXA)Statistical analysis:all data were analyzed using SPSS 20.0statistical software and were represented by mean ± standard deviation.the results of P<0.05 was considered statistically significant.Results1.Clinical and experimental research have shown that the formation of FMC is an important mechanism to maintain normal bone mineralization, but the specific mechanism of FMC involvement in the pathogenesis of OP/PMOP is still unknown. Renal deficiency was regarded as key point to onset of OP/PMOP in TCM. So the clinical curative effect and function mechanism of Reinforcing Kidney Chinese medicine needed be studied.2.There was statistical difference of MGP m RNA、BMD、β-CTX、PINP between osteoporosis group and non-osteoporosis group in female( P<0.05). The level of MGP m RNA in PMOP group were significantly lower compared to control group(0.835±0.415 VS4.524±0.769, P<0.001),and had a positive correlation with lumbar spine bone mineral density(r=0.376,P=0.000) and estradiol level(r=0.227,P=0.013). No significant correlation was founded between the serum MGP m RNA and age,BMI,β-CTX,PINP,Ca,P,PTH in both group.3.Compared with normal group,the levels of serum Fetuin-A and MGP,the lumbar m RNA expression of BMP2 and Runx2 was significantly lower while MGP m RNA was higher in PMOP group.The level of serum BMP2, Runx2 and the lumbar m RNA expression of Fetuin-A in the two groups expressed no statistical significance(P>0.05).Multivariate logistic regression analysis showed that lumbar m RNA expression of MGP, BMP2 and Runx2 correlated with BMD(OR 1.016,95% CI0.809-0.991,P = 0.029; OR 1.230,95% CI 1.063-1.424, P = 0.015;OR 1.107,95%CI1.016-1.205, P = 0.048,respectively).Fetuin-A,MGP, BMP2 and Runx2 were all showed in bone marrow stromal cell cytoplasm obverseved by Immunohistochemistry.Besides, Fetuin-A, BMP2 and Runx2 were showed in the surrounding trabecular bone osteoblasts while MGP were showed in bone osteoclasts. Under the light microscope,the positive expression was brown yellow granules.Compared with normal group, MGP levels in the PMOP group was significantly higher and BMP2 and Runx2 level was significantly lower(P<0.05 or P<0.01).The level of Fetuin-A in the two groups was not significant difference(P>0.05).4.After 24 weeks treatment,B group and C group can effectively improve the clinical symptoms of the patients(P < 0.05), and group C can quickly relieve pain(P < 0.01). The BMD of C group and B group in lumbar and femoral neck were all improved significantly(P<0.05),and the BMD of C group in lumbar increased more significantly(P<0.01).Fetuin-A and MGP were improved obviously in C group and B group(P<0.05 or P < 0.01),while no obvious changes of Fetuin-A and MGP in A group(P>0.05).The serum bone metabolism markers of patients in three groups have no significant difference(P >0.05)Conclusions1.MGP may be involved in the pathogenesis of postmenopausal osteoporosis and E2 may influence the regulation of serum MGP level2.FMC is likely affect bone mineralization and involved in the pathogenesis of PMOP. Under the guidance of TCM theory, the application of nourishing kidney therapy for postmenopausal osteoporosis has a certain theoretical basis and also experimental research support.3.The synthesis of serum FMC and the aggregation of MGP in local bone tissue may affect the BMP2/Smad/Runx2 pathway and inhibite the normal bone mineralization, thus affecting the occurrence of PMOP.4. Epimedium capsules can improve kidney yang deficiency syndrome and increase BMD in postmenopausal patients. The effect and dosage of Epimedium capsules was positively correlated, its mechanism may associated with increasing serum levels of FMC. |
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