目前还不了解COLIA1基因影响骨密度和骨折危险性的机制。不同基因型可能与Sp1有不同结合能力，从而影响到COLIA1 mRNA的转录。
四、转化生长因子(TGF-β)基因
TGF-β是调节骨形成和骨吸收的重要细胞因子。TGF-β基因由7个外显子组成，应用PCR-SSCP和DNA测序技术，发现骨质疏松妇女有多个位点的突变，如第5外显子76位上的C→T突变，使TGF-β前肽上的263位苏氨酸变化为异亮氨酸，(Thr263-Ile)，更有意义的是位于第5外显子上游8个碱基处的内含子序列中缺失了一个C(713-8delC)，与正常妇女相比，这种突变类型多见于骨质疏松妇女，且骨转换加快。713-8delC突变可能会影响mRNA剪接，造成TGF-β合成障碍，从而降低TGF-β对破骨细胞的抑制作用，使骨转换加快〔16〕。此外，在该基因信号序列区内新发现一个因T→C突变而使第10位上的亮氨酸被脯氨酸替换，CC基因型的绝经后妇女腰椎骨密度和血清TGF-β高于TT或TC型，T等位基因多见于骨质疏松者〔17〕。
五、其他候选基因
1.白细胞介素-6(IL-6)基因：IL-6对破骨细胞分化和功能起重要作用。它是介导雌激素不足引起骨丢失的重要细胞因子之一。IL-6基因可能也是调节骨量的候选基因之一。IL-6基因3’侧翼有一可变数目串联重复序列(VNTR)，可有A-F6种片断长度，其多态性与骨密度有关。C/F基因型妇女比F/F型有更高的腰椎骨量，且这一现象不仅见于绝经后，也见于绝经前妇女，提示该IL-6基因多态性可能与骨量峰值有关〔18〕。
2.白细胞介素-1(IL-1)受体拮抗剂基因：IL-1受体拮抗剂(IL-ra)能阻断去卵巢鼠的骨丢失，IL-1受体拮抗剂基因(IL-1RN)可能对绝经后早期的骨丢失有一定的遗传调控作用。人IL-1RN位于2q13-14，有4个外显子。第2内含子中有一VNTR，按重复数目可分为A1-A5五种等位基因。一项研究发现A2等位基因与腰椎骨量丢失速度和低骨量有关〔19〕。
多态性VNTR与骨量关系的内在机制尚待研究，在糖尿病中发现胰岛素基因的表达受胰岛素VNTR等位基因的调节〔20〕。此外，串联重复数目可能也会影响转录活性和mRNA稳定性。IL-6基因中的T/A重复序列也可能是另一位于IL-6基因附近的基因多态性标记，而IL-1RN第2内含子的VNTR更可能含有 与某些潜在蛋白质结合的位 点，它也可能与位于2号 染色体附近的致病基 因有不平衡连锁。
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