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糖皮质激素治疗患者小梁骨丢失的组织形态计量学长期纵向研究:泼尼松与地夫可特对比

A histomorphometric long-term longitudinal study of trabecular bone loss in glucocorticoid-treated patients: prednisone versus deflazacort.

作者信息

LoCascio V, Ballanti P, Milani S, Bertoldo F, LoCascio C, Zanolin E M, Bonucci E

机构信息

Istituto di Semeiotica e Nefrologia Medica, Università di Verona, Ospedale Policlinico, Italy.

出版信息

Calcif Tissue Int. 1998 Mar;62(3):199-204. doi: 10.1007/s002239900417.

Abstract

Administration of a corticosteroid with minor osteopenic effects is considered an effective prevention of glucocorticoid osteoporosis. Deflazacort, an oxazolinic derivative of prednisolone, is reported to be less harmful to cancellous bone mass than other equally effective corticosteroids. However, comparative long-term studies, particularly on trabecular bone, are needed before a smaller detrimental effect on bone of deflazacort can be unequivocally confirmed. We conducted such a prospective long-term study using histomorphometric analysis of iliac bone. For the study, 18 pairs of nonimmobilized patients, matched for age, sex, menopausal state, corticosteroid dose, and type and severity of the disease, were randomly submitted to treatment with therapeutically equivalent doses of prednisone or deflazacort. Bone biopsies from iliac crest were taken before and at various times during treatment. In order to represent the time-related trabecular bone loss and find out possible differences between patients on prednisone or deflazacort, a previously described model of bone loss kinetics was applied. No significant differences in biochemical indices of bone turnover or in histomorphometric variables between prednisone- and deflazacort-treated patients were recorded before treatment. The mean duration of treatment at the final biopsy was similar for prednisone and deflazacort (15.8 and 15.2 months, respectively). Patients showed evident clinical improvement with both treatments. Osteoid and resorption surfaces showed no significant differences throughout the observation period in any of the 18 pairs. On the contrary, both steroids induced a significant decrease in trabecular bone, although the bone loss rate induced by prednisone was significantly higher than that induced by deflazacort (P < 0.05). The kinetics of bone loss and the different osteopenic effects of the two drugs are described by the negative exponential function fitted to data from patients never previously given glucocorticoids; the model yields highly significant difference (P approximately equal to 0.01) between the two drugs and allows estimation of the difference even 3 years after the beginning of treatment (-3.0%/year versus -1.1%/year for prednisone and deflazacort, respectively). This prospective long-term study confirms that an exponential model accurately describes the trabecular bone loss induced by long-term corticosteroid treatment and demonstrates that deflazacort, at therapeutically effective doses, induces less trabecular bone loss than prednisone.

摘要

使用具有轻微骨质减少作用的皮质类固醇被认为是预防糖皮质激素性骨质疏松症的有效方法。据报道,泼尼松龙的恶唑啉衍生物地夫可特对松质骨量的损害比其他同等有效的皮质类固醇要小。然而,在明确证实地夫可特对骨骼的有害作用较小之前,需要进行比较长期的研究,特别是关于小梁骨的研究。我们使用髂骨组织形态计量分析进行了这样一项前瞻性长期研究。在该研究中,18对年龄、性别、绝经状态、皮质类固醇剂量以及疾病类型和严重程度相匹配的未固定患者,被随机给予治疗等效剂量的泼尼松或地夫可特。在治疗前和治疗期间的不同时间采集髂嵴骨活检样本。为了表示与时间相关的小梁骨丢失并找出泼尼松或地夫可特治疗患者之间可能存在的差异,应用了先前描述的骨丢失动力学模型。治疗前,泼尼松和地夫可特治疗患者的骨转换生化指标或组织形态计量学变量均未记录到显著差异。最后一次活检时的平均治疗持续时间,泼尼松和地夫可特相似(分别为15.8个月和15.2个月)。两种治疗方法均使患者临床症状明显改善。在整个观察期内,18对中的任何一对患者的类骨质和吸收表面均无显著差异。相反,两种类固醇均导致小梁骨显著减少,尽管泼尼松引起的骨丢失率显著高于地夫可特(P < 0.05)。从未接受过糖皮质激素治疗的患者的数据拟合的负指数函数描述了骨丢失动力学和两种药物不同的骨质减少作用;该模型得出两种药物之间存在高度显著差异(P约等于0.01),并且即使在治疗开始3年后也能估计出差异(泼尼松和地夫可特分别为-3.0%/年和-1.1%/年)。这项前瞻性长期研究证实,指数模型准确描述了长期皮质类固醇治疗引起的小梁骨丢失,并表明在治疗有效剂量下,地夫可特引起的小梁骨丢失比泼尼松少。

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