Conti A, Sartorio A, Ferrero S, Ferrario S, Ambrosi B
Laboratorio Sperimentale di Ricerche Endocrinologiche, Centro Auxologico Italiano, IRCCS, Milano, Italy.
J Endocrinol Invest. 1996 Feb;19(2):127-30. doi: 10.1007/BF03349848.
Serum bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and aminoterminal propeptide of type III procollagen (PIIINP) levels were determined in 8 patients with autoimmune disorders (2 with systemic lupus erythematosus, 3 with rheumatoid arthritis, 2 with Sjögren's syndrome and 1 with mixed connective tissue disease) before and after 1, 2 and 4 months of treatment with oral prednisone (at a dosage of 1 mg/kg bw/day, p.o. during the first month, then reduced to 0.1-0.2 mg/kg bw/day). Before treatment mean serum BGP (mean +/- SE: 5.3 +/- 0.4 ng/ml) and ICTP (2.8 +/- 0.2 ng/ml) levels were similar to those recorded in an age and sex matched control group (n = 40: 5.4 +/- 0.1 ng/ml and 4.1 +/- 0.3 ng/ml, respectively). On the other hand, serum PIIINP levels (2.2 +/- 0.3 ng/ml) were significantly (p < 0.008) lower than those found in controls (3.3 +/- 0.2 ng/ml). During glucocorticoid therapy, serum BGP levels significantly decreased after 1 month (2.9 +/- 0.4 ng/ml; P < 0.001), but returned to baseline values after 2 and 4 months of treatment (4.7 +/- 0.4 ng/ml and 5.3 +/- 0.3 ng/ml, respectively). On the contrary, no significant changes were observed in serum ICTP levels during treatment (1st month: 2.7 +/- 0.4 ng/ml; 2nd month: 3.0 +/- 0.4 ng/ml; 4th month: 2.4 +/- 0.3 ng/ml). Serum PIIINP mean concentration significantly decreased after 1 (1.6 +/- 0.3 ng/ml; P < 0.004) and 2 months of glucocorticoid administration (1.5 +/- 0.2 ng/ml; P < 0.01); after 4 months, serum PIIINP levels were again reduced as before therapy (1.8 +/- 0.2 ng/ml). In conclusion, our study shows the presence of normal bone turnover indexes and of altered collagen synthesis in patients with autoimmune disorders. The use of high doses of oral steroids is associated with a prompt decrease of bone formation and collagen synthesis, without any significant changes in bone resorption; however, the negative effects on bone formation and collagen synthesis seem to revert after lowering corticosteroid dosage. Serial determinations of the markers of bone and collagen turnover are able to give useful and reliable information on the peripheral effects of steroids excess.
测定了8例自身免疫性疾病患者(2例系统性红斑狼疮、3例类风湿关节炎、2例干燥综合征和1例混合性结缔组织病)在口服泼尼松治疗前及治疗1、2和4个月后的血清骨钙素(BGP)、I型胶原羧基末端交联肽(ICTP)和III型前胶原氨基末端前肽(PIIINP)水平(第1个月剂量为1mg/kg体重/天,口服,之后减至0.1 - 0.2mg/kg体重/天)。治疗前,血清BGP平均水平(均值±标准误:5.3±0.4ng/ml)和ICTP(2.8±0.2ng/ml)与年龄和性别匹配的对照组(n = 40:分别为5.4±0.1ng/ml和4.1±0.3ng/ml)记录的水平相似。另一方面,血清PIIINP水平(2.2±0.3ng/ml)显著低于对照组(3.3±0.2ng/ml)(p < 0.008)。在糖皮质激素治疗期间,血清BGP水平在1个月后显著下降(2.9±0.4ng/ml;P < 0.001),但在治疗2个月和4个月后恢复至基线值(分别为4.7±0.4ng/ml和5.3±0.3ng/ml)。相反,治疗期间血清ICTP水平未观察到显著变化(第1个月:2.7±0.4ng/ml;第2个月:3.0±0.4ng/ml;第4个月:2.4±0.3ng/ml)。糖皮质激素给药1个月(1.6±0.3ng/ml;P < 0.004)和2个月后(1.5±0.2ng/ml;P < 0.01),血清PIIINP平均浓度显著下降;4个月后,血清PIIINP水平再次降至治疗前水平(1.8±0.2ng/ml)。总之,我们的研究表明自身免疫性疾病患者存在正常的骨转换指标和胶原合成改变。高剂量口服类固醇的使用与骨形成和胶原合成迅速下降相关,而骨吸收无任何显著变化;然而,降低皮质类固醇剂量后,对骨形成和胶原合成的负面影响似乎会恢复。连续测定骨和胶原转换标志物能够提供关于类固醇过量外周效应的有用且可靠信息。