Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Department of Pediatrics, School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Bone. 2025 Jan;190:117329. doi: 10.1016/j.bone.2024.117329. Epub 2024 Nov 9.
Tetracycline labeling for bone biopsy facilitates quantification of the pace of new bone production. As tetracycline labeling needs to be done prior to biopsy, it cannot be used to assess bone turnover in patients presenting with fractures, yet knowing turnover rate in patients experiencing fractures - especially in those with chronic kidney disease (CKD) - may guide appropriate medical therapy after surgical repair. Therefore, we sought to determine the diagnostic accuracy of static markers of bone turnover relative to tetracycline labeling in a pediatric and adult cohort of patients with chronic kidney disease (CKD) undergoing iliac crest biopsy with histomorphometry.
We evaluated two cohorts, one of 147 children and young adults ages 18±10 and another of 151 adults ages 49±13 who had undergone iliac crest biopsy with tetracycline labeling for clinical indications of CKD-mineral and bone disorders. We used bone formation rate relative to bone surface (BFR/BS) based on double tetracycline labeling as our gold standard marker of bone turnover. A blinded investigator used light microscopy without fluorescence to measure static bone turnover parameters. We compared the area under the ROC curve (AUC), sensitivity, and specificity of each static parameter with low and high bone turnover based on BFR/BS.
In the pediatric and adult cohorts, 35 (24 %) and 70 (46 %) had low bone turnover, respectively, and 18 (12 %) and 30 (20 %) had high bone turnover, respectively. The static parameters with the greatest AUCs for low and high turnover were osteoblast surface/bone surface (Ob.S/BS), osteoclast surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV), and osteoid thickness (O.Th.) in both cohorts. Ob.S/BS had the highest AUC for low and high turnover in the pediatric cohort (0.8204 and 0.8678, respectively) whereas Oc.S/BS had the highest AUC for low turnover (0.8325) and ES/BS had the highest AUC for high turnover (0.7360) in the adult cohort.
Static measures of histomorphometry that do not rely on tetracycline bone labeling can identify low and high bone turnover in children and adults with CKD with moderate to high accuracy. This approach may allow assessment of bone turnover in the setting of clinical fractures where clinicians may have access to bone tissue but where tetracycline labeling is not available.
四环素骨活检标记物有助于定量新骨生成的速度。由于四环素标记需要在活检之前进行，因此不能用于评估骨折患者的骨转换，但了解骨折患者（尤其是慢性肾脏病 (CKD) 患者）的转换率可能会指导手术修复后的适当药物治疗。因此，我们试图在接受髂嵴活检和组织形态计量学检查的患有慢性肾脏病 (CKD) 的儿童和成人队列中，确定相对于四环素标记的静态骨转换标志物的诊断准确性。
我们评估了两个队列，一个队列包括 147 名年龄在 18±10 岁的儿童和年轻人，另一个队列包括 151 名年龄在 49±13 岁的成年人，这些患者均因 CKD-矿物质和骨代谢紊乱的临床指征而接受了四环素标记的髂嵴活检。我们使用双四环素标记的骨形成率相对于骨表面 (BFR/BS) 作为骨转换的金标准标记物。一位经过盲法培训的研究者使用无荧光的光学显微镜来测量静态骨转换参数。我们比较了每个静态参数的曲线下面积（AUC）、敏感性和特异性，以根据 BFR/BS 将其分为低骨转换和高骨转换。
在儿科和成人队列中，分别有 35 名（24%）和 70 名（46%）患者的骨转换较低，分别有 18 名（12%）和 30 名（20%）患者的骨转换较高。在两个队列中，低和高骨转换的 AUC 值最大的静态参数是成骨细胞表面/骨表面 (Ob.S/BS)、破骨细胞表面/骨表面 (Oc.S/BS)、吸收表面/骨表面 (ES/BS)、类骨质表面/骨表面 (OS/BS)、类骨质体积/骨体积 (OV/BV) 和类骨质厚度 (O.Th.)。在儿科队列中，Ob.S/BS 对低和高骨转换的 AUC 值最高（分别为 0.8204 和 0.8678），而 Oc.S/BS 对低骨转换的 AUC 值最高（0.8325），ES/BS 对高骨转换的 AUC 值最高（0.7360）。
不依赖于四环素骨标记的组织形态计量学静态测量可以以中等至较高的准确性识别 CKD 儿童和成人中的低骨转换和高骨转换。这种方法可能允许在临床骨折的情况下评估骨转换，在这种情况下，临床医生可能可以获得骨组织，但无法进行四环素标记。
