Reid I R, Nicholson G C, Weinstein R S, Hosking D J, Cundy T, Kotowicz M A, Murphy W A, Yeap S, Dufresne S, Lombardi A, Musliner T A, Thompson D E, Yates A J
Department of Medicine, University of Auckland, New Zealand.
Am J Med. 1996 Oct;101(4):341-8. doi: 10.1016/s0002-9343(96)00227-6.
The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies.
We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions.
N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated.
Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.
强效双膦酸盐类药物在骨Paget病的治疗中前景广阔，但目前在大多数国家仅以肠胃外制剂形式提供。需要一种耐受性良好的口服疗法。此外，目前可用的疗法均未经过严格证明可治愈该疾病特有的溶骨性骨病变。阿仑膦酸钠是一种强效新型口服氨基双膦酸盐，在初步研究中已显示出对Paget病有良好效果。
我们报告了一项针对55例Paget病患者进行的为期6个月的双盲、随机对照研究，比较每日口服40mg阿仑膦酸钠与安慰剂的效果。通过测量骨转换的生化指标（血清碱性磷酸酶和尿N-端肽）以及对溶骨性骨病变进行盲法放射学评估来确定疗效。
接受阿仑膦酸钠治疗的患者尿N-端肽排泄量下降了86%，血清碱性磷酸酶下降了73%，而接受安慰剂治疗的患者则保持稳定（两组间这两个指标的P值均<0.001）。无论患者之前是否接受过双膦酸盐治疗，反应相似。阿仑膦酸钠治疗使48%的患者碱性磷酸酶恢复正常。48%接受阿仑膦酸钠治疗的患者溶骨表现出放射学改善，而安慰剂组仅有4%改善（组间比较P = 0.02）。两组均无患者溶骨情况恶化。骨组织形态计量学表明阿仑膦酸钠倾向于使转换指标恢复正常。从12例接受阿仑膦酸钠治疗的受试者获取的骨活检中没有异常矿化的证据。该治疗耐受性良好。
口服阿仑膦酸钠似乎是治疗Paget病的一种安全有效的疗法，可使溶骨性骨病变愈合。
