Adami S, Salvagno G, Guarrera G, Montesanti F, Garavelli S, Rosini S, Lo Cascio V
Calcif Tissue Int. 1986 Oct;39(4):226-9. doi: 10.1007/BF02555208.
4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHButBP) was given intravenously (2.5-25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (C12MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2-18 months and the time to relapse did correlate to the logarithm of the dose (P less than 0.001). In the five patients previously treated for Paget's disease, an apparent resistance to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with C12MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.
对14例骨Paget病患者静脉注射4-氨基-1-羟基亚丁基-1,1-双膦酸盐（AHButBP）（2.5 - 25mg/天，共4天），其中5例患者在32个月前曾接受二氯亚甲基双膦酸盐（C12MBP）治疗。在9例先前未接受过双膦酸盐治疗的患者中，短疗程的AHButBP可使血清碱性磷酸酶和尿羟脯氨酸值降至初始值的30%。疾病的生化抑制持续2 - 18个月，复发时间与剂量的对数相关（P < 0.001）。在5例先前接受过Paget病治疗的患者中，观察到对AHButBP治疗明显耐药。然而，在这些患者中，血清碱性磷酸酶和尿羟脯氨酸均降至或甚至低于先前使用C12MBP所达到的最低点值，与复发程度无关。因此，双膦酸盐治疗后可实现的骨Paget病抑制程度似乎对每位患者都是恒定的，以至于在疾病极其活跃的患者中通常无法达到血清碱性磷酸酶和尿羟脯氨酸的正常水平。
