Chan Michael H M, Chan Paul K S, Griffith James F, Chan Iris H S, Lit Lydia C W, Wong C K, Antonio Gregory E, Liu Ester Y M, Hui David S C, Suen Michael W M, Ahuja Anil T, Sung Joseph J Y, Lam Christopher W K
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Pathology. 2006 Jun;38(3):229-35. doi: 10.1080/00313020600696231.
We investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong.
Seventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman's coefficients of rank correlation with biochemical bone markers.
Biochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone-specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900 mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort.
Both bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28-44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.
我们使用骨代谢的特定生化标志物，研究了大剂量皮质类固醇疗法对骨代谢的影响，以及香港一所大学教学医院中严重急性呼吸综合征（SARS）患者的骨坏死患病率。
根据世界卫生组织修订的SARS病例定义，对71例临床诊断为SARS的患者进行了研究，这些患者参与了2003年3月10日至6月20日期间的SARS疫情。临床诊断通过血清学检测和/或分子分析得以证实。回顾性分析骨代谢的生化标志物，使用从每位患者入院至出院期间以及随后在门诊随访时采集的系列凝血血样，采用任意时间段：（i）发热后<10天；（ii）第28 - 44天；（iii）第51 - 84天；以及（iv）发热后>90天。入院后对膝关节和髋关节进行磁共振成像，以评估这些SARS患者中骨坏死的患病率。使用受试者操作特征曲线比较以及适当的检验统计量和与骨生化标志物的Spearman等级相关系数，评估骨坏死发生的各种危险因素。
骨代谢的生化标志物显示出明显的骨吸收，发热后第28 - 44天血清C末端肽浓度（CTx）显著升高即证明了这一点。随着皮质类固醇剂量逐渐减少，CTx从第51天起开始恢复到先前的基线水平，而其他骨形成标志物，血清骨钙素和骨特异性碱性磷酸酶浓度（分别为OC和BALP）开始升高。在>90天后这种效应更为明显。7例患者出现了骨坏死的影像学证据。该队列中骨坏死的患病率为9.9%。发现总皮质类固醇剂量>1900 mg氢化可的松、>2000 mg甲泼尼龙、>13340 mg氢化可的松等效皮质类固醇疗法以及皮质类固醇治疗>18天是随后发生骨坏死的显著危险因素。该患者队列中各种骨生化标志物之间也存在显著的正相关。
骨吸收和形成标志物均无法预测随后骨坏死的发生。长时间使用高剂量氢化可的松或甲泼尼龙被证明是骨坏死的一个显著危险因素。其在该队列中的患病率与文献中报道的接受高剂量皮质类固醇疗法的SARS患者相当。血清CTx在第28 - 44天的升高与皮质类固醇的使用时间一致。血清OC和BALP在>51天的升高与皮质类固醇撤药时间一致。
