WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK.
Eur J Cancer. 2010 Feb;46(3):558-65. doi: 10.1016/j.ejca.2009.12.003. Epub 2009 Dec 22.
Breast cancer treatments have been associated with accelerated bone loss and increased osteoporosis risk. In a subgroup analysis of a randomised, double-blind, placebo-controlled study, we compared the changes in spine and total hip bone mineral density (BMD) and biochemical markers of bone turnover in women with primary breast cancer who had received standard therapy plus either oral clodronate 1600 mg/d (n=419) or placebo (n=432) for 2 years. After 2 years, spine BMD was 1.92% higher in patients who received clodronate instead of placebo (P<0.0001) and total hip BMD was 1.29% higher (P=0.002 versus placebo). Patients who received clodronate had a median 26% reduction in levels of serum N-terminal pro-peptide of type I procollagen (PINP)--a marker of bone turnover--after 2 years of therapy. This compares with a median 5% increase in patients who received placebo (P<0.0001). Effects on BMD, but not biochemical markers, persisted for up to 3 years post-treatment. Early changes in PINP were associated with changes in BMD and the likelihood of developing bone metastases. This study shows the use of oral clodronate during primary breast cancer treatment is associated with reduced bone turnover and protection against bone metastases.
乳腺癌的治疗与加速骨质流失和增加骨质疏松症风险有关。在一项随机、双盲、安慰剂对照研究的亚组分析中，我们比较了接受标准治疗加口服氯膦酸 1600mg/d（n=419）或安慰剂（n=432）治疗 2 年的原发性乳腺癌女性的脊柱和全髋骨矿物质密度（BMD）和骨转换生化标志物的变化。2 年后，接受氯膦酸盐治疗的患者脊柱 BMD 比安慰剂组高 1.92%（P<0.0001），全髋 BMD 高 1.29%（P=0.002 与安慰剂相比）。接受氯膦酸盐治疗的患者，在治疗 2 年后，血清 I 型前胶原 N 端前肽（PINP）水平（骨转换的标志物）中位数降低 26%，而接受安慰剂的患者中位数增加 5%（P<0.0001）。在治疗后长达 3 年，BMD 的变化而不是生化标志物的变化仍然存在。PINP 的早期变化与 BMD 的变化和发生骨转移的可能性相关。本研究表明，在原发性乳腺癌治疗期间使用口服氯膦酸盐可降低骨转换并预防骨转移。
