Postmenopausal Bone Mass And Hormone Therapy To Inhibit Bone Loss In Prospective Studies

Part 1 Changes of body mass during the process of ovary agingObjectiveWomen aged 35-64 year old from community were investigated and followed up once one year later,with the objective of the changes of body mass density during the process of ovary aging.Materials and methodsThe study belonged to analysis one including baseline inestigatrion and 1 year follow up.743 women aged 35-64 years who lived Beijing community attended our survey by the stratum clustering sample method.We conducted the survey by face-to-face interview with the questionnaire.The items of the questionnaire are detailed as follow:the basic conditions(such as age,career, education,income,etc),illness medical history,sex hormone treatment history, menstruation condition.Examination items:1.BMD examination:using DEXA BMD instrument made of American Lunar company.Examine the lunar 2-4(L_2-4) and femur Neck,Wards,and Troch,the total and upper site of BMD.The CV are 0.5%-1.1%。2.Serum E₂:Using the electrochemiluminescence(Elecsys 2010 automatic electrochemiluminescence instrument made of American Roche company). The cv are 6.4%of interest and 6%of intraset respectively.3.Serum Ca,P and ALP:Exaimine the serumCa,P and ALP using conventional biochemistry method,the CV are1.94%,3.13%and 5.01%of interest espectively.A year later these women were investigated again for the changes of the above situations and re-measured the above indexes.Statistics:All data were entered into database Epidata 3.02 and were analyzed by SPSS 12.0(statistics software package for social science).Qualitative data were analyzed by frequency,proportion;quantitative data were analyzed by mean and standard deviation.Chi-square test was applied to the comparison of the category data between menopausal status.Women were divided according to the menstruation condition standard by STRAW:premenopause(women's menstrual cycles are regular),early menopausal transition(women's menstrual cycles changes more than 7 days at least one cycle),late menopausal transition(amenorrhoea 2-11 months) early menopause(women without menstruation for no more than 5 years) and late postmenopause(women without menstruation over 5 years).Repeated measures modeling was used to evaluate the relationship between the lumbar and femur BMD and menopausal status.The level of statistical significance was set at p＜0.05.Results1.743 women aged 35-64 years(96.1%of the total participants) participated in he present study and were accepted for it;among which 522 women finished the follow-up,with the follow-up rate at 70.3%。2.The lumbar and femur BMD were significant different between the menopausal status(p=0.0001).The BMD of L_2-4,Neck,wards,total and upper site and as well as Troch descended as reproductive aging,the value of BMD were not different among the premenopause,early menopausal transition and late menopausal transition but statistically higher than the other groups.After one year,the BMD of all lumbar and femur declined,the BMD and total BMD declined statistically when women entered menopausal transition,the extent of late menopausal transition and early menopause was bigger than that of the other groups(p=0.0001).The most obvious site of bone loss was lumbar BMD in the menopausal transition and early menopause.The BMD changes of women at 45-54 ages were similar.3.The decline extent of Neck site was the biggest within the first 3 years from menopause as 2.6%,and as 1.6%-1.8%at the 4-10 years since menopause, followed by 0.6%;the decline extent of L_2-4 was the biggest within the first 3 years as 3.3%,and as 2.2%at the 4-5 years since menopause,followed by 0.6%-0.7%after 5 years since menopause.4.Ca,P and ALP are statistically different between the menopausal status.ALP value upgraded with reproductive aging.After one year,Ca and P declined, ALP increased,the extent is the biggest in the late menopausal transition group.ConclusionsWomen's lumbar and femur BMD begin decline when entering menopausal transition,the bone loss speed within 3-5 year of menopause,representing as high transfer bone loss. Part 2 Cohort study about the changes of bone mass based on menopausal transition early menopausal women from clinicObjectiveTo evaluate the changes of women's bone mineral density and biochemical markers of bone metabolism at menopausal transition period(age 40-55 years old, has irregular menstruation),or early menopause(age 45-60 years old, amenorrhea over six months,within five years).Materials and methods61 menopausal transition women and 47 early menopausal women were recruited from clinicl and were given the calcium medicine 900mg/day,Vit D 200 in/day,taking exercise(10 minutes once,twice a day).The research time is 5 years.2.Investigating items:1) BMD examination:using DEXA BMD instrument made of American Lunar company.Examine the lunar 2-4(L_2-4) and femur Neck,Wards,Troch.The CV are1.1%,1.7%,3.7%and 2.1%.Repeat these indexes measures once a year.2) Bone metabolism index:Examine the NTX using ELISA method from American OSTEX company.The CV are＜5%of intraset and＜10%of interest respectively.3) Serum E2:Using the electrochemiluminescence(Elecsys 2010 automatic electrochemiluminescence instrument made of American Roche company). The cv are 6.4%of interest and 6%of intraset respectively.3.Statistics:All data were entered into database Epidata3.02 and were analyzed by SPSS 12.0(statistic software package for social science),quantitative data were analyzed by mean and standard deviation;Results3.menopausal transition women's BMD at L_2-4 and Neck sites began to decline at the 3-year follow up between-1.9%and-3.9%;Wards site's BMD began to decline at the 4-year follow up between-3.2%and-5.2%. Early menopausal women's BMD at L_2-4 and Neck sites began to decline at the 1-2-year follow up between-1.2%and-8.5%,being Wards as the maximum site. 4.Menopausal transition and early menopausal women's NTX/Cr changes significantly at the 3-year follow up(p＜0.01)。ConclusionsBone loss speed at the first year after menopause,being Wards as the maximum site. Part 3 A random,double-blinded placebo study of hormone therapy on restraining from bone lossObjective1.To evaluate the effects of long-term HT starting from menopausal transition period((age of 40-55 years,having irregular menstruation) and early menopausal women(age of 45-60 years,amenorrhea between half a year and 5 years) on lumbar and femur BMD.2.To evaluate the effects of long-term HT starting from menopausal transition period(having irregular menstruation) and early menopausal women (amenorrhea between half a year and 5 years) on urinary Ca/Cr,Ntx/Cr and serum ALP.3.To evaluate the effects of long-term HT starting from menopausal transition period and early menopausal women on the whole health.Materials and methods1.124 menopausal transition women aged 40-55 years and 96 early menopausal women aged 45-60 year were randomly distributed into treatment group and placebo group.The treatment group was given E2V 1.0mg/d plus sequent MPA 6.0mg ^*12 days/month and calcium medicine 900mg/day,Vit D 200 iu/day.The placebo group was only given the calcium medicine 900mg/ day,Vit D 200 in/day,taking exercise(10 minutes once,twice a day).The research time is 5 years.2.Investigating items:1) BMD examination:using DEXA BMD instrument made of American Lunar company.Examine the lunar 2-4(L_2-4) and femur Neck,Wards,Troch.The CV are1.1%,1.7%,3.7%and 2.1%.Repeat these indexes measures once a year.2) Bone metabolism index:examine the second fasting urinary Ca/Cr using the conventional biochemistry method.Examine the NTX using ELISA method from American OSTEX company.The CV are＜5%of intraset and＜10% o finterest respectively.Examine the serum ALP,the CV are both 5.01%of intraset and interest.Serum Ca,P,Mg and ALP:Exaimine the serum Ca,P and ALP using conventional biochemistry method,the CV are1.94%,3.13%, and 5.01%of interest respectively. 3) Serum E2:Using the electrochemiluminescence(Elecsys 2010 automatic electrochemiluminescence instrument made of American Roche company). The cv are 6.4%of interest and 6%of intraset respectively.4) The osteoporosis centrum fracture:Using the image of thoracic and lumbar vertebra by Genant semi-quantify method at the 0,2 and 5 year of study.5) Examine the serum TC,TG,HDL and LDL level;fasting glucose and insulin level at the 0,1,2,3,4 and 5 year of follow up.3.Statistics:All data were entered into database Epidata3.02 and were analyzed by SPSS 12.0(statistic software package for social science).Qualitative data were analyzed by frequency,proportion;quantitative data were analyzed by mean and standard deviation;measurement data were compared by T test or ANOVA for continuous variables.Chi-square test was applied to the comparison of the category data between menopausal status using.Repeated measures modeling was used to evaluated effect of HT on the BMD as well as Ca/Cr,NTX/Cr and E2.The level of statistical significance was set at p＜0.05.ITT(intention-to-treat) analysis and PP(Per Protocol) analysis were both used.Results1.332 women were filtered,220 women were participated.Among the 96 early menopause women,29 women dropped and 38 dropped among the 124 menopausal transition.All participants were recruited ITT analysis.There were not statistically different between age,weight,educational level,the length of menopause and all sites of chronic diseases.2.E2:In the menopausal transition group,the E2 level was stable through the 5-year study and was not different from the baseline level in the HT group;the E2 level in the placebo group fluctuated with declined trend;The E2level were different in the first,third and fourth year between the two groups(p＜0.05).In the early menopause group,the E2 level after therapy was significantly higher than that of baseline(p＜0.01) and sustained the stable level;the E2 level in the placebo group did not marked change.There was significantly different between the groups in all the follow-up years expect 0 year.3.BMD:In the early menopause group,after the first year of therapy,the lumbar,femur Neck and Troch BMD increased significantly,then sustained the stable level;femur Wards BMD did not marked change;the BMD of all above sites declined in the placebo group;the BMD of all above sites were statistically different between the HT and placebo groups except the baseline. In the menopausal transition group,the BMD of all above sites after the first year of therapy increased significantly,then declined to the level of baseline; the lumbar,femur Neck and Wards BMD declined significantly in the 3-4 year of therapy,Troch BMD did not marked change.The BMD of all above sites were not statistically different between the HT and placebo group.Staging the women in to normal bone mass group and bone loss group(using the lumbar bone mass of above or under 1.062 g/ cm2 as limit),we found the BMD changes between the two groups was not significantly different except the lumbar site at the first year of follow-up.4.Bone transfer index:The urinary Ca/Cr was not different between HT and placebo group;Ntx/Cr value declined after the first year in the HT group and then sustained stably,which in the placebo group upgraded.There was significant different at the 3-5 year follow-up(p＜0.05) The serum ALP level in the HT group was significantly lower than placebo group but baseline.5.The serum lipids levels between the HT and placebo group were not significantly different,but the level of TC,TG and LDL increased significantly in the placebo group;while the level of HDL increased significantly in the HT group and decreased in the placebo group.The fasting glucose and insulin level were not significantly different between the HT and placebo group.At the sixth month,the morbidity of mammary tenderness was highest(as 61.90%in the menopausal transition HT group),then declined gradually.There were not significantly different but the first,second year(menopausal transition) and the first year(early menopause) between the HT and placebo group.The women of endometrium of≥5mm were not significantly different between the HT and placebo group in the five year study.Conclusions1.The 5 year therapy of E2V 1.0mg plus sequent MPA 6.0mg ^*12 days/month and calcium medicine 900mg/day and Vit D 200 iu/day,can increase or sustain the BMD early menopause women,staying the BMD of menopausal transition.2.The 5 year therapy of E2V 1.0mg plus sequent MPA 6.0mg ^*12 days/month and calcium medicine 900mg/day and Vit D 200 in/day have the similar effect of increasing or sustaining the BMD on the normal bone mass group and bone loss group.3.The 5 year therapy of E2V 1.0mg plus sequent MPA 6.0mg ^*12 days/month and calcium medicine 900mg/day and Vit D 200 in/day have no negative impact on serum glucose,lipid and insulin with few side-effects.