Department of Internal Medicine, Endocrine-Metabolic Sciences, and Biochemistry, University of Siena, Siena, Italy.
J Bone Miner Res. 2011 Mar;26(3):512-8. doi: 10.1002/jbmr.237.
Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar short-term efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bone-specific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions.
双膦酸盐实际上是治疗 Pagets 骨病（PDB）最常用的治疗方法。在之前的研究中，我们证明了唑来膦酸（4mg）或奈立膦酸盐（200mg）单次静脉输注，在高达 90%的对帕米膦酸盐无反应的患者中达到生化缓解的短期疗效相似。在这项研究中，我们比较了在 56 例活动期 Pagets 骨病患者中使用相同剂量的奈立膦酸盐（200mg）静脉内（连续 2 天输注 100mg）或肌内（2 个月每周注射 25mg）方案的长期（36 个月）效果。所有患者均在整个研究期间接受钙加维生素 D 补充。在 6 个月时，分别有 92.6%和 96.5%的静脉内和肌内奈立膦酸盐患者达到治疗反应[定义为碱性磷酸酶（ALP）水平正常化或总 ALP 过量降低至少 75%]。治疗反应与 6 个月时的基线 ALP 和 25-羟维生素 D[25（OH）D]水平显著相关。在基线总 ALP 或骨特异性 ALP 水平较高且 6 个月时 25（OH）D 水平较高的患者中，ALP 水平的降低幅度最大。在 12 个月时，应答率保持不变，但在 24 个月和 36 个月时逐渐下降，但两种奈立膦酸盐方案之间无显著差异。两种方案均耐受良好。唯一相关的副作用是 14%的患者出现急性期反应。总之，这些结果表明，200mg 肌内奈立膦酸盐疗程与相同剂量的静脉输注疗效相似，对于不能耐受口服双膦酸盐且不愿意或无法进行静脉输注的患者可能具有特殊价值。
