Kim Tiffany Y, Bauer Douglas C, McNabb Brian L, Schafer Anne L, Cosman Felicia, Black Dennis M, Eastell Richard
Department of Medicine, University of California, San Francisco, CA, USA.
Medical Service, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
J Bone Miner Res. 2019 May;34(5):810-816. doi: 10.1002/jbmr.3654. Epub 2019 Jan 15.
An ASBMR Task Force recommends a drug holiday for certain women treated for ≥5 years with oral alendronate or ≥3 years with intravenous zoledronic acid, with reassessment 2 to 3 years later. It is not known whether changes in bone mineral density (BMD) or bone turnover markers differ after oral or intravenous therapy. Our goal was to compare changes in BMD and procollagen type I N propeptide (PINP) after oral or intravenous bisphosphonate use. In the Fracture Intervention Trial Long-term Extension (FLEX), women who received a mean 5 years of alendronate were randomized to placebo or continued treatment. In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial Extension I (HORIZON-PFT E1), women who received 3 years of zoledronic acid were randomized to placebo or continued treatment. We examined the proportion of participants with BMD loss or PINP gain ≥ least significant change (LSC) and those whose values exceeded a threshold (T-score ≤-2.5 or PINP ≥36.0 ng/mL, a premenopausal median value). After 3 years of placebo, the FLEX group had greater mean total hip BMD decreases (-2.3% versus -1.2% in the HORIZON-PFT E1 group, p < 0.01) and greater rises in PINP (+11.6 ng/mL versus +6.7 ng/mL, p < 0.01). There was a greater proportion of individuals in FLEX with total hip BMD loss and PINP increases that exceeded LSC, and PINP values ≥36.0 ng/mL. In contrast, there were small changes in the proportion of women with femoral neck T-scores ≤-2.5 in both groups. In conclusion, 3 years after bisphosphonate discontinuation, a considerable proportion of former alendronate and zoledronic acid users had meaningful declines in total hip BMD and elevations in PINP. Despite a longer treatment course, alendronate may have a more rapid offset of drug effect than zoledronic acid. © 2018 American Society for Bone and Mineral Research.
美国骨与矿物质研究学会（ASBMR）特别工作组建议，某些接受口服阿仑膦酸钠治疗≥5年或静脉注射唑来膦酸治疗≥3年的女性应停药一段时间，2至3年后重新评估。目前尚不清楚口服或静脉治疗后骨矿物质密度（BMD）或骨转换标志物的变化是否存在差异。我们的目标是比较口服或静脉使用双膦酸盐后BMD和I型前胶原N端前肽（PINP）的变化。在骨折干预试验长期扩展研究（FLEX）中，平均接受5年阿仑膦酸钠治疗的女性被随机分为安慰剂组或继续治疗组。在唑来膦酸每年一次降低健康结局及减少骨折发生率关键性骨折试验扩展研究I（HORIZON-PFT E1）中，接受3年唑来膦酸治疗的女性被随机分为安慰剂组或继续治疗组。我们检查了BMD降低或PINP升高≥最小显著变化（LSC）以及其值超过阈值（T值≤-2.5或PINP≥36.0 ng/mL，绝经前中位数）的参与者比例。安慰剂治疗3年后，FLEX组全髋平均BMD下降幅度更大（-2.3%，而HORIZON-PFT E1组为-1.2%，p<0.01），PINP升高幅度也更大（+11.6 ng/mL对+6.7 ng/mL，p<0.01）。FLEX组中全髋BMD降低且PINP升高超过LSC以及PINP值≥36.0 ng/mL的个体比例更高。相比之下，两组中股骨颈T值≤-2.5的女性比例变化较小。总之，双膦酸盐停药3年后，相当一部分曾使用阿仑膦酸钠和唑来膦酸的患者全髋BMD出现有意义的下降，PINP升高。尽管阿仑膦酸钠的治疗疗程更长，但其药物作用的消退可能比唑来膦酸更快。©2018美国骨与矿物质研究学会。
