Association Between Serum Soluble Membrane Type Matrix Metalloproteinase-1 (MT1-MMP) Levels And Bone Mineral Density, And Biochemical Markers In Postmenopausal Women

Part One Association between serum soluble MT1-MMP levels and BMD,and biochemical markers in postmenopausal womenObjective:To investigate whether serum soluble active MT1-MMP levels co correlated inversely with BMD,serum NTX and serum BAP in postmenopausal women.Methods:Western analysis and ELISA were performed to detect serum soluble MT1-MMP levels of 206 Chinese postmenopausal women aged 43-80 years.BMD was measured by dual energy X-ray absorptiometry(DXA).Serum BAP and NTX were assayed using ELISA.Results:Cerum soluble MT1-MMP abundantly existed in human serum as protein lack of transmembrane domain.Serum MT1-MMP levels were detectable in all participants and the range of value was 221.2-863.0 ng/ml(435.6±98.2 ng/ml).We found a significant negative weaker correlation between MT1-MMP and BMD at lumbar spine, total hip(Thip),and femoral neck(FN)(all P＜0.05).After adjustment for age and BMI, We found a significant negative weaker correlation between MT1-MMP and BMD at lumbar spine(P＜0.05);the correlation with BMD at FN and Thip disappeared(all P＞0.05).Multiple linear stepwise regression analysis showed that MT1-MMP was not a determinant factor for BMD.The significant positive correlations between MT1-MMP,BAP and NTX were found,and remained significant after adjustment for age and BMI(all P＜0.05).Conclusion:Soluble MT1-MMP abundantly existed in human serum as protein lack of transmembrane domain.Circulating MT1-MMP and bone turnover markers are correlated,and serum soluble MT1-MMP levels may rise with increase in bone turnover. Part Two Effects of alendronate therapy on the Expression of serum soluble MT1-MMP and biochemical markers in postmenopausal womenObjective:To investigate the effects of alendronate therapy on the Expression of MT1-MMP and biochemical markers in postmenopausal women.Methods:We performed a randomized,double-blind clinical trial of Alendronate or control.Subjects were randomly allocated to daily 10mg Alendronate or placebo for 3 months.All subjects in both groups received a daily supplement of 600mg calcium carbonate and 125 IU vitamin D.Serum BAP and NTX were assayed using ELISA. Serum MT1-MMP was assayed using ELISA.Results:Serum MT1-MMP,BAP and NTX fell in response to alendronate(all P＜0.05). Serum MT1-MMP,BAP and NTX remained at baseline values in the placebo-treated group.Between baseline and alendronate treatment for 3 months,MT1-MMP decreased by 13.6%,BAP decreased by 33.2%,and NTX decreased 53.1%.Conclusion:MT1-MMP,BAP,and NTX decreased in response to alendronate therapy.