Hermus A R, Smals A G, Swinkels L M, Huysmans D A, Pieters G F, Sweep C F, Corstens F H, Kloppenborg P W
Department of Medicine, University Hospital Nijmegen, The Netherlands.
J Clin Endocrinol Metab. 1995 Oct;80(10):2859-65. doi: 10.1210/jcem.80.10.7559865.
We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 pre- and 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased considerably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 premenopausal patients with active CS and a control group of 18 age-matched healthy premenopausal women. However, the urinary hydroxyproline/creatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 vs. 16.2 +/- 3.5 mumol/mmol, P < 0.01). In all 9 premenopausal patients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SEM, P < 0.0001), indicating a prompt increase of osteoblast activity. Also serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked telopeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased significantly between 0 and 3 months. Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)
我们使用双能X线吸收法对20例库欣综合征（CS）患者（14例绝经前和2例绝经后女性，4例男性）进行了骨密度（BMD）测量，测量时间为手术治愈前，其中18例患者在术后也进行了定期测量（随访中位时长为36个月）。此外，对于绝经前的CS女性患者，在手术前及术后的头2年中，对其中9例患者还定期采集了空腹血样和2小时空腹尿样，以测量骨和胶原代谢的生化参数。大多数活动性CS患者存在明显的骨质减少（Z值：腰椎-1.45±1.44，股骨颈-1.50±1.02；均值±标准差）。术后3个月和6个月时未观察到BMD有一致的变化。此后，几乎所有患者的BMD都有显著增加。对于15例随访至少1年的患者，末次评估时腰椎的Z值为-0.65±1.27，股骨颈为-0.98±1.02（与治疗前值相比，两者P均<0.002）。在绝经前患者中，24个月时腰椎和股骨颈BMD的增加与年龄呈负相关（分别为r=-0.733，P<0.03；r=-0.667，P<0.05）。14例活动性CS绝经前患者组与18例年龄匹配的健康绝经前女性对照组相比，血清骨钙素、骨碱性磷酸酶、I型前胶原羧基末端前肽、III型前胶原氨基末端前肽以及I型胶原交联端肽水平无显著差异。然而，CS患者的尿羟脯氨酸/肌酐比值显著更高（24.6±9.6对16.2±3.5μmol/mmol，P<0.01）。在所有9例绝经前患者中，血清骨钙素水平在0至3个月间显著升高（从1.04±0.20至3.82±0.30nmol/L）（均值±标准误，P<0.0001），表明成骨细胞活性迅速增加。I型前胶原羧基末端前肽、III型前胶原氨基末端前肽、I型胶原交联端肽的血清水平以及尿羟脯氨酸/肌酐比值在0至3个月间也显著升高。此后这些水平逐渐下降。我们得出结论，大多数活动性库欣综合征患者腰椎和股骨颈存在明显的骨质减少。（摘要截短至400字）
