绝经后妇女MMP-2和TIMP-2水平及其与骨密度和骨代谢指标的关系

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目的探讨绝经后妇女血清基质金属蛋白酶2(MMP-2)和组织金属蛋白酶抑制因子2 (TIMP-2)水平及其与骨密度和骨代谢指标的关系。方法对192名48~65岁绝经后妇女用酶联免疫吸附法(ELISA)测定的血清MMP-2、TIMP-2以及骨碱性磷酸酶(BAP)、骨钙素、Ⅰ型胶原交联C端肽(CTx),尿Ⅰ型胶原交联N端肽(NTx),计算MMP-2/TIMP-2比值,用双能X线吸收法(DEXA)测定腰椎正位,股骨颈,Ward三角和大粗隆的骨密度,按WHO标准将绝经后妇女分为骨密度正常、低骨量和骨质疏松3组。结果(1)绝经后妇女骨质疏松患者血清MMP-2的水平(1 388±121)μg/L高于骨密度正常组(1 126±141)μg/L(P<0.05),而TIMP-2的水平(44.3±38.2)μg/L稍低于骨密度正常组(47.3±30.2)μg/L(P>0.05)。(2)血清MMP-2和MMP-2/TIMP-2比值与腰椎正位和Ward三角骨密度、血清BAP和骨钙素呈负相关(均P<0.05),和尿NTx/Cr呈正相关(P<0.05),MMP-2/TIMP-2比值还与股骨颈骨密度呈负相关(P<0.05)。TIMP-2与腰椎正位和Ward三角骨密度、血清BAP和骨钙素呈正相关(均P<0.05),和尿NTx/ Cr呈负相关(P<0.05)。在校正年龄和体重指数后,TIMP-2与腰椎正位骨密度和骨钙素无相关性(P>0.05)。(3)骨质疏松组中血清MMP-2和MMP-2/TIMP-2比值与腰椎正位、股骨颈和Ward三角骨密度、血清BAP和骨钙素呈负相关(均P<0.05),和尿NTx/Cr呈正相关(均P<0.05),TIMP-2和Ward三角骨密度和BAP呈正相关(均P<0.05);在低骨量组中仅MMP-2与腰椎正位和Ward三角骨密度、骨钙素呈负相关(P<0.05),和尿NTx/Cr呈正相关(P<0.05),MMP-2/TIMP-2比值与Ward三角骨密度和血清BAP呈负相关(均P<0.05)。结论绝经后女性尤其是骨质疏松症妇女血清MMP-2和MMP-2/TIMP-2比值与骨密度和骨代谢指标BAP、骨钙素和尿NTx/Cr具有关联性,血清MMP-2和MMP-2/TIMP-2比值增高可能为绝经后骨质疏松症伴随骨代谢转换过程增快的表现。 Objective To investigate the relationship between serum matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) levels and bone mineral density and bone metabolism in postmenopausal women. Methods Serum levels of MMP-2, TIMP-2 and bone alkaline phosphatase (BAP), osteocalcin and type Ⅰ collagen in 192 postmenopausal women aged 48-65 years were measured by enzyme-linked immunosorbent assay (ELISA) The ratio of MMP-2 / TIMP-2 was calculated by CTx and urine NTx. The lumbar spine, femoral neck, Ward triangle and femoral neck were measured by dual energy X-ray absorptiometry (DEXA) Large trochanter bone mineral density, according to WHO standards will be divided into normal bone mineral density, low bone mass and osteoporosis in 3 groups. Results (1) The serum level of MMP-2 in the postmenopausal women with osteoporosis was higher than that in the normal BMD group (1 126 ± 141) μg / L (1 388 ± 121) μg / L, 2 level (44.3 ± 38.2) μg / L was slightly lower than that of the normal BMD group (47.3 ± 30.2) μg / L (P> 0.05). (2) The serum MMP-2 and MMP-2 / TIMP-2 ratios were negatively correlated with BMD, BAP and osteocalcin (P <0.05) P <0.05). The ratio of MMP-2 / TIMP-2 also had a negative correlation with femoral neck BMD (P <0.05). There was a positive correlation between TIMP-2 and bone mineral density (BMD), serum BAP and osteocalcin (P <0.05), but negatively correlated with urine NTx / Cr (P <0.05). After adjusting for age and body mass index, there was no correlation between TIMP-2 and orthopedic bone mineral density and osteocalcin (P> 0.05). (3) The serum MMP-2 and MMP-2 / TIMP-2 ratios in osteoporosis group were negatively correlated with BMD, serum BAP and osteocalcin in lumbar spine, femoral neck and Ward triangle (all P <0.05) (P <0.05). The BMD of TIMP-2 and Ward triangle was positively correlated with BAP (all P <0.05). In the low bone mass group only MMP-2 positively correlated with lumbar spine and Ward triangle Bone mineral density, osteocalcin (P <0.05), and NTx / Cr urine (P <0.05). The ratio of MMP-2 / TIMP-2 was negatively correlated with Ward triangular bone mineral density and serum BAP <0.05). Conclusions The serum MMP-2 and MMP-2 / TIMP-2 ratios in postmenopausal women, especially those with osteoporosis, are closely related to bone mineral density and BAP, osteocalcin and urinary NTx / Cr. Serum MMP- Increased MMP-2 / TIMP-2 ratio may be the result of postmenopausal osteoporosis with the process of bone metabolism conversion.
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