青岛地区成年人I型胶原交联氨基端肽(NTx)生物参考区间的建立

Establishment of Biological Reference Intervals for Type I Collagen Cross-Linked N-Telopeptide (NTx) in Adults in the Qingdao Region

摘要: 目的：调查青岛地区健康成年人的I型胶原交联氨基端肽(NTx)水平状况，建立本地区实验室的健康人群NTx的年龄和性别相关参考区间。方法：本研究为单中心临床研究，采用回顾性研究方法，收集在青岛大学附属医院检验科进行体检的18~80岁的健康体检的志愿者为参考人群，根据CLSI C28-A3及WS/T402-2024《临床实验室定量检验项目参考区间的制定》标准制定纳排标准，按性别和绝经前后分为男性、绝经前女性和绝经后女性组，以10岁为一个年龄段分为18~30岁组、31~40岁组、41~50岁组、51~60岁组，≥60岁组。通过全自动生化免疫分析仪检测青岛地区成年人群尿液中NTx含量，以非参数方法计算出参考区间。结果：本研究共纳入957例健康体检的志愿者，其中男性440名，女性517名(绝经前女性334名，绝经后女性183名)。通过比较不同性别间的Cr、NTx/Cr，得出男女间Cr及NTx/Cr存在差异，按性别不同制定参考区间，男性Cr参考区间为12.13~29.12 mmol/L，NTx/Cr参考区间为13.16~53.31 nM BCE/mM肌酐；女性Cr参考区间为2.02~22.55 mmol/L，NTx/Cr参考区间为12.18~58.25 nM BCE/mM肌酐。按是否绝经分为绝经前女性与绝经后女性，与男性组比较三组间均存在差异，绝经前女性NTx/Cr参考区间为10.83~49.61 nM BCE/mM肌酐，绝经后女性NTx/Cr参考区间为19.61~86.17 nM BCE/mM肌酐。按照年龄建立分组，男性分为18~50岁和>50岁两组，参考区间分别为13.54~53.35 nM BCE/mM肌酐、12.77~53.86 nM BCE/mM肌酐；女性分为18~50岁和>50岁两组，参考区间分别为10.74~50.21 nM BCE/mM肌酐、15.67~86.16 nM BCE/mM肌酐。总体上，随着年龄增长，参考个体肌酐水平逐渐下降，NTx/Cr水平逐渐升高。而男性的肌酐水平较女性高，在女性绝经前，NTx与男性差异并不大，绝经后女性NTx明显升高。与试剂盒提供参考区间相比，本研究男性患者参考区间范围小，未绝经女性参考区间更广，而绝经后女性参考区间范围小于试剂盒提供区间。结论：(1) 青岛地区健康成年人Cr、U-NTx/Cr的参考区间在不同性别、不同年龄段人群中存在差异，应当建立不同性别、年龄段Cr及NTx/Cr的参考区间。(2) 青岛地区健康成年人NTx/Cr参考区间与试剂盒提供区间存在差异，应建立本地区人群的NTx/Cr参考区间。

Abstract: Objective: To investigate the levels of type I collagen cross-linked N-telopeptide (NTx) in healthy adults in the Qingdao area and to establish age- and sex-specific reference intervals for NTx in the healthy population of the local area for the laboratory. Methods: This single-center clinical study adopted a retrospective research approach. Healthy volunteers aged 18~80 years who underwent physical examinations in the Clinical Laboratory of the Affiliated Hospital of Qingdao University were selected as the reference population. Inclusion and exclusion criteria were formulated according to the CLSI C28-A3 guidelines and WS/T402-2024 “Establishment of Reference Intervals for Quantitative Laboratory Tests.” Participants were divided by sex and menopausal status into male, premenopausal female, and postmenopausal female groups. They were further stratified into age groups by decade: 18~30, 31~40, 41~50, 51~60, and ≥60 years. Urinary NTx levels in the adult population of Qingdao were measured using a fully automated biochemical immunoanalyzer, and reference intervals were calculated using non-parametric methods. Results: This study included 957 healthy volunteers, comprising 440 males and 517 females (334 premenopausal, 183 postmenopausal). Comparison of Cr and NTx/Cr between different sexes revealed differences. Therefore, sex-specific reference intervals were established. The reference interval for male Cr was 12.13~29.12 mmol/L, and for NTx/Cr was 13.16~53.31 nM BCE/mM creatinine. The reference interval for female Cr was 2.02~22.55 mmol/L, and for NTx/Cr was 12.18~58.25 nM BCE/mM creatinine. When grouped by menopausal status (premenopausal females, postmenopausal females, and males), differences were found among all three groups. The NTx/Cr reference interval for premenopausal females was 10.83~49.61 nM BCE/mM creatinine, and for postmenopausal females was 19.61~86.17 nM BCE/mM creatinine. Age-specific grouping was also performed. Males were divided into 18~50 years and >50 years groups, with reference intervals of 13.54~53.35 nM BCE/mM creatinine and 12.77~53.86 nM BCE/mM creatinine, respectively. Females were divided into 18~50 years and >50 years groups, with reference intervals of 10.74~50.21 nM BCE/mM creatinine and 15.67~86.16 nM BCE/mM creatinine, respectively. Overall, with increasing age, creatinine levels in reference individuals gradually decreased, while NTx/Cr levels gradually increased. Male creatinine levels were higher than those in females. NTx levels in premenopausal females were not significantly different from those in males, but NTx levels increased markedly in postmenopausal females. Compared to the reference intervals provided by the kit, the reference interval for males in this study was narrower, the interval for premenopausal females was wider, and the interval for postmenopausal females was narrower than the kit-provided intervals. Conclusion: (1) The reference intervals for Cr and U-NTx/Cr in healthy adults in the Qingdao area differ by sex and age group. Therefore, specific reference intervals for Cr and NTx/Cr should be established for different sexes and age groups. (2) The reference intervals for NTx/Cr in healthy adults in the Qingdao area differ from those provided by the kit. It is necessary to establish local population-specific reference intervals for NTx/Cr.