Department of Orthopaedic Surgery, Hospital for Special Surgery, Weill Cornell Medicine, New York City, NY, USA.
Center for Musculoskeletal Surgery, Corporate Member of Freie, Charité - Universitätsmedizin Berlin, Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Arch Orthop Trauma Surg. 2024 Aug;144(8):3291-3301. doi: 10.1007/s00402-024-05459-3. Epub 2024 Aug 6.
Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure.
A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs.
127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031).
This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.
目前，评估骨质量的有效工具仍然匮乏，而评估骨质量的标准方法需要进行有创性的活检。如果有一种非侵入性的、术前可用的骨质量评估方法，将具有重要的临床价值。本研究旨在探讨骨形成标志物血清骨碱性磷酸酶（BAP）和骨吸收标志物尿胶原交联 N-末端肽（uNTX）与体积骨密度（vBMD）、荧光晚期糖基化终产物（fAGEs）和骨微结构的相关性。
采用前瞻性数据对接受腰椎融合术的患者进行了横断面分析。在术前采集了 BAP 和 uNTX。在腰椎进行定量 CT（QCT，vBMD≤120mg/cm 骨质疏松/骨量减少）。从后上髂嵴采集骨活检，并通过多光子荧光显微镜评估 fAGEs，通过微计算机断层扫描（µCT）评估骨微结构。采用 Spearman ρ评估 BAP/uNTX 与 vBMD、fAGEs 和 µCT 参数之间的相关性。通过受试者工作特征（ROC）分析评估 BAP 和 uNTX 作为骨质疏松/骨量减少的预测因子。采用多元线性回归模型，校正年龄、性别、BMI、种族和糖尿病等混杂因素，确定 BAP/uNTX 与 fAGEs 之间的相关性。
共分析了 127 例前瞻性入组的患者（50.4%为女性，年龄 62.5 岁，BMI 为 28.7kg/m）。uNTX（ρ=-0.331，p<0.005）和 BAP（ρ=-0.245，p<0.025）随皮质 fAGEs 降低而降低，uNTX（ρ=-0.380，p<0.001）随小梁 fAGEs 降低而降低。BAP 和 uNTX 与 vBMD 无显著相关性。BAP 和 uNTX 的 ROC 分析区分骨质疏松/骨量减少的 AUC 分别为 0.477 和 0.561。在多元分析中，校正混杂因素后，uNTX 与增加的小梁 fAGEs 呈负相关（β=0.923；p=0.031）。
本研究表明，骨转换标志物与 fAGEs 呈负相关。uNTX 和 BAP 均不能预测脊柱的骨质疏松/骨量减少。uNTX 反映了胶原特性，可能与 vBMD 具有互补作用，作为脊柱手术中骨质量评估的一种非侵入性工具。
