Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
The Permanente Medical Group, Oakland, CA, USA.
BMC Musculoskelet Disord. 2020 Dec 3;21(1):801. doi: 10.1186/s12891-020-03672-w.
Bisphosphonate (BP) therapy has been associated with atypical femur fracture (AFF). However, the threshold of treatment duration leading to increased AFF risk is unclear. In a retrospective cohort of older women initiating BP, we compared the AFF risk associated with treatment for at least three years to the risk associated with treatment less than three years.
We used observational data from a large population of female members of an integrated healthcare system who initiated oral BP during 2002-2014. Women were retrospectively followed for incident AFF confirmed by radiologic adjudication. Demographic data, pharmacologic exposures, comorbidity, bone density, and fracture history were ascertained from electronic health records. Inverse probability weighting was used to estimate risk differences comparing the cumulative incidence (risk) of AFF if women discontinued BP within three years to the cumulative incidence of AFF if women continued BP for three or more years, adjusting for potential time-dependent confounding by the aforementioned factors.
Among 87,820 women age 45-84 years who initiated BP (mean age 68.6, median T-score - 2.6, 14% with prior major osteoporotic fracture), 16,180 continued BP for three or more years. Forty-six confirmed AFFs occurred during follow-up in the two groups. AFF-free survival was greater for BP treatment < 3 years compared to treatment ≥3 years (p = 0.004 comparing areas under survival curves). At five years, the risk of AFF was 27 per 100,000 (95% confidence interval, CI: 8-46) if women received BP treatment < 3 years and 120 per 100,000 (95% CI: 56-183) if women received BP treatment ≥3 years (risk difference 93 per 100,000, 95% CI: 30-160). By ten years, the risks were 27 (95% CI: 8-46) and 363 (95% CI: 132-593) per 100,000 for BP treatment < 3 and ≥ 3 years, respectively (risk difference 336 per 100,000, 95% CI: 110-570).
Bisphosphonate treatment for 3 or more years was associated with greater risk of AFF than treatment for less than 3 years. Although AFFs are uncommon among BP-treated women, this increased risk should be considered when counseling women about long-term BP use. Future studies should further characterize the dose-response relationship between BP duration and incident AFF and identify patients at highest risk.
双膦酸盐 (BP) 治疗与非典型股骨骨折 (AFF) 有关。然而，导致 AFF 风险增加的治疗持续时间阈值尚不清楚。在一项对开始接受 BP 治疗的老年女性的回顾性队列研究中，我们比较了至少治疗 3 年与治疗少于 3 年与 AFF 风险的关系。
我们使用了来自大型综合医疗系统的女性成员的大量观察性数据，这些女性在 2002 年至 2014 年期间接受了口服 BP 治疗。通过放射学裁决确认了经证实的 AFF 后，对女性进行了回顾性随访。从电子健康记录中确定了人口统计学数据、药物暴露情况、合并症、骨密度和骨折史。使用逆概率加权来估计如果女性在三年内停止 BP 治疗与如果女性继续 BP 治疗三年或更长时间相比，AFF 累积发生率（风险）的差异，调整了上述因素的潜在时间依赖性混杂。
在 87820 名 45-84 岁开始接受 BP 治疗的女性中（平均年龄 68.6 岁，中位数 T 分数-2.6，14%有过主要骨质疏松性骨折），16180 名女性继续 BP 治疗 3 年或更长时间。在两组中，随访期间发生了 46 例确诊的 AFF。BP 治疗<3 年的 AFF 无病生存率高于治疗≥3 年（比较生存曲线下面积，p=0.004）。在五年时，如果女性接受 BP 治疗<3 年，AFF 的风险为每 100,000 人 27 例（95%置信区间：8-46），如果女性接受 BP 治疗≥3 年，AFF 的风险为每 100,000 人 120 例（95%置信区间：56-183）（风险差异为 93 例/100,000 人，95%置信区间：30-160）。在十年时，如果女性接受 BP 治疗<3 年和≥3 年，AFF 的风险分别为每 100,000 人 27 例（95%置信区间：8-46）和 363 例（95%置信区间：132-593）（风险差异为 336 例/100,000 人，95%置信区间：110-570）。
BP 治疗 3 年或以上与 AFF 风险增加有关，而治疗少于 3 年则风险较低。尽管 BP 治疗的女性中 AFF 并不常见，但在为女性提供关于长期 BP 使用的咨询时，应考虑这种增加的风险。未来的研究应进一步描述 BP 持续时间与 AFF 发生率之间的剂量反应关系，并确定风险最高的患者。
