骨質疏鬆症是中老年婦女的嚴重健康問題，台灣隨著人口老化，將面臨骨質疏鬆症帶來的龐大醫療和 社會成本支出。定期的骨礦物質密度(bone mineral density，BMD)檢測雖可評估與預測骨質疏鬆症與骨 折機率，但BMD 的變化需要較久的時間，且僅代表骨形成與骨分解平衡之後的結果，無法反應骨骼實際代謝狀況，而骨骼代謝生化指標可早期反應骨骼代謝狀況，更有效的預測骨質疏鬆症與骨折發生 機率。近年來的研究已發現多個與BMD 相關的基因單核.酸多型性(single nucleotide polymorphism， SNP)，但仍缺乏基因多型性對骨骼代謝生化指標影響之相關研究，有鑒於骨骼代謝生化指標的高靈敏度，與在早期預防與治療骨質疏鬆症的重要角色，本二年期研究將針對台灣停經後婦女，探討(1)相關 基因SNP對骨形成指標血液bone-specific alkaline phosphatase 與osteocalcin 的影響；(2)相關基因SNP 對骨分解指標deoxypyridinoline crosslinks (Dpd)與pyridinoline crosslinks (Pyd)的影響；(3)相關基因SNP 與骨骼代謝指標對BMD 的交互影響；(4)骨質疏鬆症患者與同年齡對照組骨骼代謝生化指標的差異。本研究第一年將召募200名罹患骨質疏鬆症與200 名對照組停經後婦女，分析骨骼代謝指標，第二年將分析相關基因SNP。
Many polymorphisms of genes were reported to associate with osteoporosis, yet few studies have tested its combined effects for association with bone mineral density (BMD). Six polymorphisms were chosen for this osteoporosis study, including TNFα-857 (rs1799724), TNFα-308 (rs1800469), TGFβ1-509 (rs1800247), osteocalcin (rs1800629), PTH (rs6254), PTH (rs6256), The relation between several combined polymorphisms in different genomic regions and BMD variation was addressed. For all women combined, the proportion of low BMD among low, middle, and high BMI groups was significantly different. The combined genotypes with the largest difference in occurrence of low BMD were determined for different numbers of combined SNPs. Our data suggest that several polymorphisms of genes involved in osteoporosis pathway, that located on different chromosome and formed statistic-linked SNPs, together account for a higher occurrence of the low BMD.