继发性甲状旁腺功能亢进患者甲状旁腺切除术后骨代谢标志物的短期变化

Changes of bone metabolic markers in uremic patients with secondary hyperparathyroidism before and after parathyroidectomy

目的分析甲状旁腺切除加前臂移植手术治疗尿毒症继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)患者在手术前后骨代谢标志物的短期变化情况,为SHPT时骨病的发病机制及诊治提供依据。方法回顾性分析2015年7月~2016年1月在南京医科大学第一附属医院接受甲状旁腺切除(parathyroidectomy,PTX)加自体前臂移植术的难治性SHPT患者。收集患者术前的基线资料以及术后第3天的骨代谢标志物资料,包括骨代谢调控激素:维生素D、全段甲状旁腺激素(intact parathyroid hormone,iPTH)、降钙素(calcitonin,CT);骨形成标志物:碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(osteocalcin,OC);骨吸收标志物:Ⅰ型胶原N末端肽(type I collagen crosslinked N-telopeptides,NTX)和Ⅰ型胶原C端肽(type I collagen cross-linked C-telopeptides,CTX)。分析骨代谢指标间的相关性,及手术前后骨代谢标志物的变化情况。结果共50例接受PTX手术的严重SHPT患者纳入本研究,其中男性32例,女性18例。术前基线资料显示,患者的相关骨代谢标志物血磷、血清iPTH、ALP、OC、CT、NTX和CTX均高于正常水平,分别为(2.10±0.41)mmol/L、(1861.55±920.21)ng/L、283.55(155.53,721.78)U/L、290.8(220,300)ng/ml、(89.66±50.83)pg/ml、6.0(4.69,6.00)μg/L和1191.5(860.4,1200.0)μg/L。相关性分析结果显示:术前iPTH与ALP(r=0.782,P<0.001),iPTH与NTX(r=0.758,P<0.001),ALP与OC(r=0.637,P<0.001),NTX与CTX(r=0.749,P<0.001)及OC与NTX(r=0.311,P=0.03)之间均呈正相关。PTX术后3天,iPTH、CT、CTX分别降至11.30(5.42,23.40)ng/L、(63.17±44.20)pg/ml、1.68(1.28,2.33)μg/L均较前明显降低(P值分别为0.001,0.017,0.001),OC升至300(300,300)ng/ml,较术前明显升高(P=0.001)。结论严重SHPT时,成骨细胞和破骨细胞呈偶联性明显活化,骨形成和骨吸收均活跃,骨转换水平增高。PTX术后短期内,成骨细胞活性进一步增强,破骨细胞活性下调。

Objective To analyze the short-term variation of bone metabolic markers after parathyroidectomy（PTX） and forearm transplantation; to comprehend the pathogenesis and to improve the diagnosis and treatment of metabolic bone disease in uremic patients with secondary hyperparathyroidism（SHPT）. Methods A total of 50 patients treated with PTX for intractable SHPT in the First Affiliated Hospital of Nanjing Medical University from July 2015 to January 2016 were enrolled in this study. Their baseline clinical data,bone metabolism markers including serum intact parathyroid hormone（PTH）, calcitonin（CT）, alkaline phosphatase（ALP）, osteocalcin（OC）, type I collagen N-terminal peptide（NTX） and type I collagen C-terminal peptide（CTX） before and after PTX for 3 days were retrospectively analyzed. The correlation between bone metabolic markers and changes of bone metabolic markers after PTX were also analyzed. Results Preoperative bone metabolic markers including serum phosphorus（2.10±0.41 mmol/L）, iPTH（1861.55±920.21 ng/L）,ALP [283.55（155.53, 721.78） U/L], OC [290.8（220, 300） ng/ml], CT（89.66±50.83 pg/mL）, NTX [6.0（4.69,6.00） μg/L], and CTX [1191.5（860.4, 1200.0） μg/L] were all increased in the patients. Correlation study of the preoperative bone metabolic markers showed that iPTH and ALP（r=0.782, P〈0.001）, iPTH and NTX（r=0.758, P〈0.001）, ALP and OC（r=0.637, P〈0.001）, NTX and CTX（r=0.749, P〈0.001）, and OC and NTX（r=0.311, P =0.03） were positively correlated. After PTX for 3 days, serum iPTH, CT and CTX decreased to11.30（5.42, 23.40） ng/L, 63.17±44.20 pg/mL, and 1.68（1.28, 2.33） μg/L respectively（P〈0.05, compared to the values before PTX）; OC increased to 300（300, 300） ng/mL（P〈0.01, compared to the value before PTX）.Conclusions In uremic patients with severe SHPT, both osteoblasts and osteoclasts were activated, resulting in the hyperactivity of bone formation and resorption. Bone turnover was then increased. In the short-term period after PTX, osteoblast activity increased further and osteoclast activity decreased.