Nagasaka S, Sugimoto H, Nakamura T, Kusaka I, Fujisawa G, Sakuma N, Tsuboi Y, Fukuda S, Honda K, Okada K, Ishikawa S, Saito T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Clin Endocrinol (Oxf). 1997 Aug;47(2):215-21. doi: 10.1046/j.1365-2265.1997.2401045.x.
Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis.
Two year prospective follow-up study in patients with Graves' disease.
Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls.
Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation.
Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months.
Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.
Graves病甲状腺毒症患者存在骨代谢异常已有充分文献记载，但对其恢复的精确时间进程仍知之甚少。本研究旨在阐明甲状腺毒症患者骨表现尤其是皮质骨以及骨代谢标志物的纵向改善情况。
对Graves病患者进行为期两年的前瞻性随访研究。
连续纳入10例Graves病患者（7例男性，3例女性，平均（±标准误）年龄39.3±3.9岁），接受抗甲状腺药物治疗。13例年龄和性别匹配的病情缓解患者作为对照。
通过放大X线片上掌骨的精细皮质骨条纹和腰椎骨密度（BMD）测量评估骨表现。监测尿脱氧吡啶啉（dPYR）和血清I型胶原吡啶啉交联端肽结构域（ICTP）作为骨吸收标志物，以及血清骨钙素（OC）、I型前胶原羧基末端前肽（PICP）和碱性磷酸酶（ALP）作为骨形成标志物。
开始治疗后1个月内，初始升高的游离甲状腺激素水平恢复正常。治疗前掌骨条纹指数为1.89±0.16，高于对照组的0.49±0.12（P<0.0001）；该指数逐渐降至1.00±0.20（12个月）和0.48±0.12（24个月）。腰椎BMD Z值从-0.22±0.46升至0.21±0.47（12个月）和0.68±0.48（24个月）（P = 0.0029）。治疗前，尿dPYR和血清ICTP浓度远高于对照值（dPYR，升高553%；ICTP，升高396%，P<0.0001），在第2个月迅速下降。血清OC、PICP和ALP起初也显著高于对照组（OC，升高287%；PICP，升高225%；ALP，升高196%），并一直升高至4或8个月。
未经治疗的Graves病甲状腺毒症患者存在骨吸收和皮质骨条纹。甲状腺激素水平正常化后，骨吸收迅速改善。相比之下，加速的骨形成持续至少4 - 8个月，提示骨重塑的正性解偶联。这种占主导地位的骨形成可导致皮质骨条纹改善和小梁骨骨密度增加。
