Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, OX, OX3 7LD, UK.
Osteoporos Int. 2014 Jan;25(1):77-83. doi: 10.1007/s00198-013-2420-8. Epub 2013 Jun 28.
Patients with cognitive impairment (CI) often do not receive secondary fracture prevention. Use of zoledronic acid led to a similar reduction in re-fracture risk but the survival benefit was limited to those without CI.
We tested whether the effects of zoledronic acid (Zol) on re-fracture and mortality differed in patients presenting with a hip fracture by cognitive status.
We used data from the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial, of yearly intravenous 5 mg Zol vs. placebo in patients presenting with a hip fracture. Primary outcome was new fracture and secondary outcome mortality. Short Portable Mental Status Questionnaire (SPMSQ) with a cut-point of >2 was used to identify CI. Fine-Gray models for competing events were fitted to study the effect of Zol on re-fracture and Cox regression for death. A multiplicative term was introduced to study a potential interaction between treatment and cognitive status on outcomes.
Baseline SPMSQ of 1,966/2,127 (92.4%) patients was measured. Three hundred fifty (17.8%) had CI, balanced between treatment arms. In the placebo arm, there was similar fracture incidence between those with and without CI (15.4 vs. 12.3%, p = 0.26). There was no significant interaction for the effect of CI on Zol and re-fracture (p = 0.66). CI was associated with higher 1-year mortality (12.6 vs. 4.3%, p < 0.001) and the interaction was bordering significance (interaction, p = 0.066). Zol prolonged survival only in patients with normal cognitive status [HR 0.56 (95% CI 0.40-0.80)] and not in those with CI [HR 0.90 (95% CI 0.59-1.38)].
While these results require confirmation, the findings support the use of bisphosphonates in patients with osteoporotic fracture and CI expected to live for more than 6 months.
认知障碍（CI）患者常得不到二级骨折预防。唑来膦酸的应用可降低再骨折风险，但生存获益仅限于无 CI 的患者。
我们检测了认知状态不同的髋部骨折患者使用唑来膦酸（Zol）对再骨折和死亡率的影响是否存在差异。
我们使用了每年静脉注射 5mg Zol 与安慰剂治疗髋部骨折患者的骨质疏松性骨折复发预防研究（HORIZON-RFT）的数据。主要结局是新发骨折，次要结局是死亡率。采用简短精神状态问卷（SPMSQ），截断值>2 分来识别 CI。竞争风险的 Fine-Gray 模型用于研究 Zol 对再骨折的影响，Cox 回归用于研究死亡。引入一个乘积项来研究治疗和认知状态对结局的潜在交互作用。
共纳入 2127 例患者的基线 SPMSQ 评分，其中 1966 例（92.4%）患者的评分可评估。350 例（17.8%）患者有 CI，两组间平衡。安慰剂组，有 CI 和无 CI 的患者骨折发生率相似（15.4%比 12.3%，p=0.26）。CI 对 Zol 和再骨折影响的交互作用无统计学意义（p=0.66）。CI 与较高的 1 年死亡率相关（12.6%比 4.3%，p<0.001），且交互作用有显著趋势（p=0.066）。Zol 仅在认知状态正常的患者中延长生存时间[HR 0.56（95%CI 0.40-0.80）]，而在有 CI 的患者中无生存获益[HR 0.90（95%CI 0.59-1.38）]。
虽然这些结果需要进一步证实，但研究结果支持在预期生存时间超过 6 个月的骨质疏松性骨折合并 CI 的患者中使用双膦酸盐。
