Oslo University Hospital, Norwegian Research Centre for Women's Health, Oslo, Norway.
Department of Physical Health and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
Osteoporos Int. 2023 Aug;34(8):1369-1379. doi: 10.1007/s00198-023-06752-4. Epub 2023 Apr 27.
We investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.
To investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index.
Norwegian women aged 50-89 in 2005-2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis.
Of 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91-0.99) for bisphosphonate use and 0.60 (95% CI: 0.47-0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29-0.61) compared with the unexposed population.
In population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.
我们研究了挪威双膦酸盐和地舒单抗使用与髋部骨折风险之间的关系。这些药物在临床试验中可预防骨折，但它们在人群中的效果尚不清楚。我们的研究结果表明，治疗女性的髋部骨折风险降低。对高危人群进行治疗可能预防未来的髋部骨折。
研究在调整基于药物的合并症指数后，双膦酸盐和地舒单抗是否降低了挪威女性首次髋部骨折的风险。
纳入 2005 年至 2016 年期间年龄在 50-89 岁的挪威女性。挪威处方数据库（NorPD）提供了双膦酸盐、地舒单抗和其他药物暴露的数据，用于计算 Rx-Risk 合并症指数。挪威所有医院治疗的所有髋部骨折信息均可获得。使用年龄作为时间尺度，采用灵活参数生存分析，同时考虑双膦酸盐和地舒单抗的时变暴露情况。个体随访至髋部骨折或死亡、移民、90 岁（以先发生者为准）或 2016 年 12 月 31 日。Rx-Risk 评分作为时变协变量纳入分析。其他协变量包括婚姻状况、教育程度以及除骨质疏松症以外的其他适应证下使用双膦酸盐或地舒单抗的情况。
在 1044661 名女性中，77755 名（7.2%）曾使用过双膦酸盐，4483 名（0.4%）使用过地舒单抗。完全调整后的风险比（HR）分别为 0.95（95%置信区间（CI）：0.91-0.99）和 0.60（95%CI：0.47-0.76）。与人群相比，双膦酸盐治疗 3 年后和地舒单抗治疗 6 个月后髋部骨折风险显著降低。与未暴露人群相比，曾使用过双膦酸盐的地舒单抗使用者的骨折风险最低：HR 为 0.42（95%CI：0.29-0.61）。
在基于人群的真实世界数据中，在调整合并症后，使用双膦酸盐和地舒单抗的女性髋部骨折风险低于未暴露人群。治疗持续时间和治疗史影响骨折风险。
