肢端肥大症患者骨转换标记物和骨平衡变化及其影响因素分析  

Changes and influencing factors of bone turnover markers and bone remodeling balance in acromegaly patients

作　　者：陈焕 张燕[2] 刘梦思 张子为[2] 冯文焕[2] 李平[2] 朱大龙 Chen Huan;Zhang Yan;Liu Mengsi;Zhang Ziwei;Feng Wenhuan;Li Ping;Zhu Dalong(Nanjing Drum Tower Hospital,Chinese Academy of Medical Science&Graduate School of Peking Union Medical College,Nanjing 210008,China;Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]中国医学科学院北京协和医学院研究生院南京鼓楼医院内分泌科,南京210008 [2]南京大学医学院附属鼓楼医院内分泌科,南京210008

出　　处：《中华医学杂志》2021年第33期2600-2605,共6页National Medical Journal of China

基　　金：江苏省自然科学基金项目(BK20181116)。

摘　　要：目的明确肢端肥大症患者骨转换标记物水平和骨平衡状态的变化及与疾病活动性的相关性。方法收集2012年9月至2019年10月南京鼓楼医院确诊的肢端肥大症患者68例(治疗后随访资料完善者39例)。同时选择年龄、性别、体质指数(BMI)匹配的肾上腺无功能瘤30例作为对照组。比较两组血清钙、磷、甲状旁腺激素(PTH)、骨转换标记物水平及骨重塑指数;肢端肥大症患者根据术后生化是否完全缓解分为非缓解组和缓解组,分别比较治疗前后骨代谢相关指标变化;利用相关性及回归模型分析肢端肥大症患者骨转换标记物的影响因素。结果与对照组相比,肢端肥大症患者血钙及血磷水平高,血清PTH水平低(均P<0.01)。骨钙素[45.98(31.98,60.27)比15.83(12.74,19.96)ng/ml,P<0.01]、血清Ⅰ型原胶原N-端前肽(P1NP)[115.50(72.64,145.90)比36.45(30.45,44.28)ng/ml,P<0.01]与血清Ⅰ型胶原C-末端肽交联(CTX)[1.12(0.79,1.56)比0.37(0.30,0.50)ng/ml,P<0.01]水平均高于对照组。肢端肥大症患者骨重塑指数明显高于对照组[4.27(1.31,5.99)比0.03(-0.38,0.63),P<0.01]。血清胰岛素样生长因子1(IGF-1)水平是骨钙素(β=0.610,P<0.001)、P1NP(β=0.601,P<0.001)及CTX(β=0.596,P<0.001)的独立影响因素。非缓解组和缓解组经治疗生化异常改善后,血钙及血磷均较治疗前显著下降(均P<0.05)。非缓解组和缓解组治疗后血清PTH水平较前升高,而骨转换标记物及骨平衡Z值均降低,但仅在缓解组上述指标治疗前后比较差异有统计学意义(均P<0.05)。生化异常完全缓解的肢端肥大症患者骨转换指标及骨重塑指数可恢复至接近对照组水平(均P>0.05)。结论肢端肥大症患者呈非PTH依赖的钙磷代谢异常及高骨转换状态,总体骨形成大于骨吸收,并且与肢端肥大症疾病活动性密切相关。治疗后随着循环生长激素(GH)及IGF-1水平下降,高骨转换状态改善达到骨平衡状态。Objective To evaluate the changes of bone turnover markers and bone remodeling balance in acromegaly patients and their associations with disease activity.Methods A total of 68 patients diagnosed with acromegaly in Nanjing Drum Tower Hospital from September 2012 to October 2019 were collected(39 patients had complete follow-up data after treatment).Meanwhile,30 patients with non-functional adrenal adenoma matched for age,sex,and body mass index(BMI)were also included as controls.Serum calcium,phosphorus,parathyroid hormone(PTH),bone turnover markers[osteocalcin,C-terminal telopeptide of type 1 collagen(CTX)and procollagen type 1 N-terminal propeptide(P1NP)],and bone remodeling index were detected and compared between the two groups.Further,acromegaly patients were subdivided into remission and non-remission groups according to whether the patient achieved complete remission after treatment.Univariate and multivariate linear regression analysis was used to determine the independent predictors of bone turnover markers.Results At baseline,acromegaly patients had higher serum calcium,phosphorus and lower PTH levels than controls(all P<0.01).Moreover,Acromegaly patients had higher serum osteocalcin[45.98(31.98,60.27)ng/ml vs 15.83(12.74,19.96)ng/ml,P<0.01],P1NP[115.50(72.64,145.90)ng/ml vs 36.45(30.45,44.28)ng/ml,P<0.01]and CTX than controls[1.12(0.79,1.56)ng/ml vs 0.37(0.30,0.50)ng/ml,P<0.01].Meanwhile,the bone remodeling index in acromegaly patients was significantly increased compared with controls[4.27(1.31,5.99)vs 0.03(-0.38,0.63),P<0.01].Multivariate linear regression analysis revealed that serum insulin-like growth factor 1(IGF-1)was an independent predictor for osteocalcin(β=0.610,P=0.000),P1NP(β=0.601,P=0.000)and CTX(β=0.596,P=0.000).After treatment,serum calcium and phosphorus in both remission group and non-remission group decreased(all P<0.05).Likewise,serum level of PTH increased,while osteocalcin,PINP,CTX,and bone remodeling index decreased in remission and non-remission groups,but the differences wer

关 键 词：肢端肥大症 骨转换标记物 骨平衡 生长激素 胰岛素样生长因子1 

分 类 号：R584.11[医药卫生—内分泌]