Department of Endocrinology and Metabolism, Loyola University Medical Center.
Endocr Pract. 2013 Nov-Dec;19(6):989-94. doi: 10.4158/EP12425.OR.
Atypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U. S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.
A retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.
Eleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were -2.225 (±1.779) and -2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (-0.0084 ± 0.03 gm/cm2).
The current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy.
长期使用双磷酸盐治疗绝经后骨质疏松症会导致非典型股骨骨折和颌骨骨质疏松症。美国临床内分泌医师协会指南建议，对于中度风险患者，在使用双磷酸盐治疗 4 至 5 年后和对于高风险患者 10 年后，应进行药物停药，但关于安全停药时间的数据很少。最近美国食品和药物管理局的观点建议治疗时间为 3 至 5 年。我们的目的是描述一组进行药物停药的患者并确定骨折风险。
对 2005 年至 2010 年间开始双磷酸盐药物停药的 209 名患者进行了回顾性病历审查。收集的数据包括骨密度（BMD）、骨转换标志物、维生素 D 状况以及骨折的临床和影像学报告。
209 名患者中有 11 名（5.2%）发生骨折。他们的平均年龄为 69.36 岁（±15.58），平均腰椎和股骨颈 T 评分分别为-2.225（±1.779）和-2.137（±0.950）。所有患者在 6 个月时碱性磷酸酶骨特异性显著增加，骨折组更为明显（3.0±0.6083μg/L 比 1.16±1.9267μg/L）。在 4 年期间，整个队列的平均腰椎 BMD 没有显著变化，但股骨颈 BMD 在第 2 年有统计学意义的下降（-0.0084±0.03gm/cm2）。
目前开始双磷酸盐停药的做法需要进一步评估，特别是在真实环境中。老年患者和骨密度极低的患者在药物停药期间需要密切随访。骨折、早期骨转换标志物显著升高和/或 BMD 下降应恢复骨质疏松症治疗。
