Mokhber Aghaghia, Hall Elizabeth, Uzelac Aleksandra, Salmena Leonardo, Cheung Angela, Lubinski Jan, Narod Steven A, Kotsopoulos Joanne
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
Queen's School of Medicine, Queen's University, Kingston, ON, Canada.
Bone Rep. 2024 Sep 6;22:101802. doi: 10.1016/j.bonr.2024.101802. eCollection 2024 Sep.
Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among mutation carriers.
Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of osteoporotic fracture (FRAXmajor) and fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann-Whitney test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD.
Among 701 women with a mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) < 0.0001). In a subset with BMD measurement ( = 50), low serum OPG was associated with a significantly lower BMD T-score (-1.069 vs. -0.318; = 0.04).
Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in mutation carriers.
骨保护素（OPG）在抑制破骨细胞形成和骨吸收方面发挥着重要作用。研究报告称，携带该基因突变的女性中OPG水平较低，因此，她们可能面临更大的骨骼骨质流失风险。因此，我们在携带该基因突变的人群中，研究了循环OPG与两个经过验证的骨骼健康标志物之间的关联：1）骨折风险评分（FRAX）和2）骨密度（BMD）。
本分析纳入了有血液样本和临床数据的女性。采用酶联免疫吸附测定法（ELISA）对血清OPG（pg/mL）进行定量，并使用基于网络的算法估计骨质疏松性骨折（FRAXmajor）和髋部骨折（FRAXhip）的10年风险（%）。对于一部分女性，之前通过双能X线吸收法（DXA）评估了腰椎骨密度（T值）。采用曼-惠特尼U检验评估OPG与FRAX评分之间的关联，同时采用线性回归评估OPG与BMD之间的关联。
在701名携带该基因突变的女性中，OPG水平与FRAX评分之间存在显著（且出乎意料的）正相关（FRAXmajor：低OPG组为2.12，高OPG组为2.53，P<0.0001；FRAXhip：低OPG组为0.27，高OPG组为0.44，P<0.0001）。在有骨密度测量值的亚组（n = 50）中，低血清OPG与显著更低的骨密度T值相关（-1.069对-0.318，P = 0.04）。
我们的研究结果表明，先天OPG水平较低的女性可能存在骨密度降低的风险，而骨密度是骨疾病的金标准标志物。由于我们队列中的女性年龄较轻，有必要进行正在进行的研究，以重新评估携带该基因突变人群中OPG与FRAX之间的关联。
