Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal.
Bone. 2012 Dec;51(6):981-9. doi: 10.1016/j.bone.2012.08.129. Epub 2012 Sep 5.
Osteocalcin (OC) is the most abundant non-collagenous bone protein and is determinant for bone mineralization. We aimed to compare OC bone expression and serum factors related to its carboxylation in hip fragility fracture and osteoarthritis patients. We also aimed to identify which of these factors were associated with worse mechanical behavior and with the hip fracture event.
In this case-control study, fragility fracture patients submitted to hip replacement surgery were evaluated and compared to a group of osteoarthritis patients submitted to the same procedure. Fasting blood samples were collected to assess apolipoproteinE (apoE) levels, total OC and undercarboxylated osteocalcin (ucOC), vitamin K, LDL cholesterol, triglycerides and bone turnover markers. The frequency of the apoε4 isoform was determined. Femoral epiphyses were collected and trabecular bone cylinders drilled in order to perform compression mechanical tests. Gene expression of bone matrix components was assessed by quantitative RT-PCR analysis.
64 patients, 25 submitted to hip replacement surgery due to fragility fracture and 39 due to osteoarthritis, were evaluated. Bone OC/collagen expression (OC/COL1A1) ratio was significantly lower in hip fracture compared to osteoarthritis patients (p<0.017) adjusted for age, gender and body mass index. Moreover, OC/COL1A1 expression ratio was associated with the hip fracture event (OR ~0; p=0.003) independently of the group assigned, or the clinical characteristics. Apoε4 isoform was more frequent in the hip fracture group (p=0.029). ucOC levels were higher in the fracture group although not significantly (p=0.058). No differences were found regarding total OC (p=0.602), apoE (p=0.467) and Vitamin K (p=0.371). In hip fracture patients, multivariate analysis, adjusted for clinical characteristics, serum factors related to OC metabolism and gene expression of bone matrix proteins showed that low OC/COL1A1 expression ratio was significantly associated with worse trabecular strength (β=0.607; p=0.013) and stiffness (β=0.693; p=0.003). No association was found between ucOC and bone mechanics. Moreover, in osteoarthritis patients, the multivariate analysis revealed that serum total OC was negatively associated with strength (β=-0.411; p=0.030) and stiffness (β=-0.487; p=0.009).
We demonstrated that low bone OC/COL1A1 expression ratio was an independent predictor of worse trabecular mechanical behavior and of the hip fracture event. These findings suggest that in hip fracture patients the imbalance of bone OC/COL1A1 expression ratio reflects disturbances in osteoblast activity leading to bone fragility.
骨钙素（OC）是最丰富的非胶原骨蛋白，是决定骨矿化的关键因素。我们旨在比较髋部脆性骨折和骨关节炎患者的 OC 骨表达和与羧化相关的血清因子。我们还旨在确定这些因素中哪些与更差的机械性能以及与髋部骨折事件相关。
在这项病例对照研究中，接受髋关节置换手术的脆性骨折患者进行了评估，并与接受相同手术的骨关节炎患者组进行了比较。采集空腹血样以评估载脂蛋白 E (apoE) 水平、总 OC 和未羧化骨钙素 (ucOC)、维生素 K、LDL 胆固醇、甘油三酯和骨转换标志物。确定 apoε4 同工型的频率。采集股骨骨骺并在骺部钻孔以进行压缩力学测试。通过定量 RT-PCR 分析评估骨基质成分的基因表达。
评估了 64 名患者，25 名因脆性骨折而接受髋关节置换手术，39 名因骨关节炎而接受髋关节置换手术。与骨关节炎患者相比，髋部骨折患者的骨 OC/COL1A1 表达（OC/COL1A1）比值显着降低（p<0.017），并调整了年龄、性别和体重指数。此外，OC/COL1A1 表达比值与髋部骨折事件相关（OR~0；p=0.003），与所分配的组或临床特征无关。apoε4 同工型在髋部骨折组中更为常见（p=0.029）。尽管不显着（p=0.058），但骨折组的 ucOC 水平较高。总 OC（p=0.602）、apoE（p=0.467）和维生素 K（p=0.371）无差异。在髋部骨折患者中，调整临床特征、OC 代谢相关的血清因子和骨基质蛋白的基因表达的多变量分析显示，低 OC/COL1A1 表达比值与较差的小梁强度（β=0.607；p=0.013）和刚度（β=0.693；p=0.003）显着相关。ucOC 与骨力学之间没有关联。此外，在骨关节炎患者中，多变量分析显示血清总 OC 与强度呈负相关（β=-0.411；p=0.030）和刚度（β=-0.487；p=0.009）。
我们证明，低骨 OC/COL1A1 表达比值是小梁机械性能恶化和髋部骨折事件的独立预测因子。这些发现表明，在髋部骨折患者中，OC/COL1A1 表达比值的失衡反映了成骨细胞活性的紊乱，导致骨脆弱。
