Hosking David
Division of Mineral Metabolism, City Hospital, Nottingham NG5 1PB, UK.
Bone. 2006 Feb;38(2 Suppl 2):S3-7. doi: 10.1016/j.bone.2005.11.011. Epub 2006 Jan 10.
Paget's disease is a relatively common high-turnover metabolic bone disease that can serve as a model for osteoporosis and other metabolic bone diseases in investigation of therapeutic strategies to normalize bone turnover. Aims of treatment include rapid normalization of bone formation and resorption to prevent loss of mechanical integrity. Treatment will also reduce pain, while long-term maintenance of normal turnover may prevent long-term complications. Newer bisphosphonates have high antiresorptive potency and increased retention in bone, permitting a strategy of intermittent intravenous (IV) administration in achieving and maintaining normal bone turnover. In pivotal zoledronic acid Paget's disease trials, patients received a single 15-min IV infusion of zoledronic acid 5 mg (ZOL 5 mg) or risedronate 30 mg/day orally for 2 months. Treatment with ZOL 5 mg was associated with significant improvement in serum alkaline phosphatase, normalization in both the short and long term, and significant prolongation of biochemical therapeutic response in long-term follow-up. No changes in serum creatinine levels were observed with either treatment, and no clinically significant renal abnormalities were reported. Intermittent IV administration of potent bisphosphonates constitutes an intriguing strategy for treatment of Paget's disease and other metabolic bone diseases.
佩吉特氏病是一种相对常见的高转换型代谢性骨病，在研究使骨转换正常化的治疗策略时，可作为骨质疏松症和其他代谢性骨病的模型。治疗目标包括使骨形成和骨吸收迅速恢复正常，以防止机械完整性丧失。治疗还将减轻疼痛，而长期维持正常的骨转换可能预防长期并发症。新型双膦酸盐具有高抗吸收效力且在骨中的保留时间增加，这使得间歇性静脉注射给药策略可用于实现和维持正常的骨转换。在关键的唑来膦酸治疗佩吉特氏病试验中，患者接受单次15分钟静脉输注5毫克唑来膦酸（ZOL 5毫克）或每日口服30毫克利塞膦酸钠，持续2个月。ZOL 5毫克治疗与血清碱性磷酸酶显著改善相关，短期和长期均恢复正常，且在长期随访中生化治疗反应显著延长。两种治疗均未观察到血清肌酐水平变化，也未报告有临床意义的肾脏异常。间歇性静脉注射强效双膦酸盐构成了一种治疗佩吉特氏病和其他代谢性骨病的有趣策略。
