绝经后妇女血清基质金属蛋白酶-1、-2和组织金属蛋白酶抑制因子-1水平及其与骨密度及骨转换生化指标的关系

Relationships between circulating matrix metalloproteinase-1, -2 and metalloproteinase-1 levels and bone biochemical markers and bone mineral density in Chinese postmenopausal women

目的探讨绝经后妇女血清成骨细胞分泌的基质金属蛋白酶1、2(MMP-1,MMP-2)和组织金属蛋白酶抑制因子1(TIMP1)与骨密度及骨转换生化指标之间的关系。方法用酶联免疫吸附试验测定297名48～80岁女性志愿者的血清MMP-1、MMP-2、TIMP-1、血清骨碱性磷酸酶(BAP)、血清骨钙素和血清Ⅰ型胶原氨基末端肽(NTX),用双能量X射线吸收测定术测定腰椎正位、L1L4总体、股骨颈、Ward′s区、总髋部的骨密度。结果(1)绝经后妇女血清MMP-1、TIMP-1水平与骨密度、骨转换生化指标无明显相关性。(2)血清MMP-2水平与骨密度呈较弱的负相关,校正年龄与体重指数后,与股骨颈、髋部骨密度的相关性消失。(3)MMP2与BAP、骨钙素、NTX正相关(相关系数分别为0.193、0.231、0.249,均P<0.01)。(4)绝经后骨质疏松症患者血清MMP2水平(1466μg/L±313μg/L)高于年龄匹配的正常对照组(1222μg/L±243μg/L)、低骨量组(1282μg/L±220μg/L)(P<0.01)。结论绝经后妇女血清MMP-2与骨转换生化指标相关联,血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。

Objective To study the serum matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels, and the correlations of MMP-1, MMP-2, and TIMP-1 with bone turn-over markers and bone mineral density (BMD) in aged postmenopausal Chinese women. Methods The serum MMP-1, MMP-2, TIMP-1, serum bone alkaline phosphatase (BAP), serum osteocalcin (OC), serum cross-linked N-telopeptides of type Ⅰ collagen (NTX) of 297 Chinese female volunteers aged 48-89 were measured using ELISA. BMD were measured using dual energy X-ray absorptiometry in aged postmenopausal Chinese women. Results (1) There were no significant negative relationships between MMP-1, TIMP-1 and BMD and bone biochemical markers. (2)A weak negative relationships were found between MMP-2 and BMD. Adjusted by age and body weight, the correlation of MMP-2 with BMD of neck of femur and hip disappeared. (3) Positive correlations between MMP-2 and BAP, OC, NTX was found (all r=0.193、0.231、0.249, P<0.01) (4) Serum MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis (1466 μg/L±313 μg/L) than in age-matched normal controls (1222 μg/L±243 μg/L) and osteopenia subjects (1282 μg/L±220 μg/L). Conclusion There are significant correlations between serum MMP-2 and bone metabolism, and MMP-2 may increase with increases in bone-turnover. The increases of serum MMP-2 appear possibly as a concomitant event in high bone turnover state, such as postmenopausal osteoporosis.