Filipponi P, Cristallini S, Policani G, Casciari C, Gregorio F
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy.
Bone. 1998 Dec;23(6):543-8. doi: 10.1016/s8756-3282(98)00133-1.
This study assessed the efficacy of 200 mg of aminohexane bisphosphonate (neridronate) administered by intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active Paget's disease of bone. Fifteen patients had never been treated with any antiresorptive agent and 17 had had unsatisfactory results from a prior clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after clodronate infusion. In the present study bone-specific alkaline phosphatase (bAp), deoxypyridinoline (dPyr), and N- and C-terminal polypeptide of collagen type 1 (Ntx, Ctx) were determined before neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 +/- 2.3 microg/L, range 31.7-92.5 (normal range 6.2-23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 +/- 4.1) and those suffering a relapse after clodronate (bAp = 48.8 +/- 2.6). Neridronate induced an average percent change from baseline in excess bAp of 68.0 +/- 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 +/- 11, 60.6 +/- 8.5, and 86.7 +/- 7.8, respectively. Markers of bone resorption declined more slowly in patients treated previously with clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after clodronate. In 15 of 21 patients requiring analgesics to alleviate bone pain, pain was reduced or completely alleviated in 8. A slight, short-lived acute phase reaction (fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that neridronate can be used safely in the treatment of patients with Paget's disease of bone either as a first bisphosphonate treatment or as retreatment for patients relapsing after clodronate.
本研究评估了静脉输注200毫克氨基己烷双膦酸盐（奈立膦酸）单剂量或连续两天分两剂给药，对32例活动性骨Paget病患者（16例男性和16例女性，平均年龄66岁）的疗效。15例患者从未接受过任何抗吸收剂治疗，17例患者先前使用氯膦酸盐治疗效果不佳。所有后一组患者均未进入缓解期（即治疗期间任何时候均未报告骨转换正常化），且在输注氯膦酸盐后6个月内完全复发。在本研究中，在给予奈立膦酸之前以及之后的1、3、6和12个月测定骨特异性碱性磷酸酶（bAp）、脱氧吡啶啉（dPyr）以及1型胶原的N端和C端多肽（Ntx、Ctx）。bAp的基础值为51.7±2.3微克/升，范围为31.7 - 92.5（正常范围6.2 - 23.6）。新的Paget病患者（bAp = 55.1±4.1）和氯膦酸盐治疗后复发的患者（bAp = 48.8±2.6）在基础状态下骨转换标志物无明显统计学差异。奈立膦酸使过量bAp相对于基线的平均百分比变化为68.0±4.3，过量dPyr、Ntx和Ctx相对于基线的平均百分比变化分别为68.1±11、60.6±8.5和86.7±7.8。先前用氯膦酸盐治疗的患者骨吸收标志物下降更缓慢，尽管过量bAp以及过量骨吸收标志物相对于基线的平均百分比下降变化与未治疗的Paget病患者记录的变化无差异。在12个月随访期间的任何时间，将对治疗的反应定义为过量bAp相对于基线下降50%或更多，27例患者（84.4%）观察到这种情况。21例患者（65.6%）实现缓解（bAp降至正常范围内），在12个月随访时12例患者维持缓解，1天或2天输注之间、新的Paget病患者与氯膦酸盐治疗后复发的患者之间均无显著差异。在21例需要镇痛药缓解骨痛的患者中，15例患者中有8例疼痛减轻或完全缓解。6例患者出现轻微、短暂的急性期反应（发热和/或关节痛）。总之，200毫克静脉注射奈立膦酸，一剂或两剂，在大多数患者中显著降低了疾病活动的生化指标，超过60%的患者bAp恢复正常。我们得出结论，奈立膦酸可安全用于骨Paget病患者的治疗，既可以作为首次双膦酸盐治疗，也可以作为氯膦酸盐治疗后复发患者的再治疗。
