Agarwal Amil R, LiBrizzi Christa L, Wessel Lauren, Thakkar Savyasachi C, Levin Adam S
Department of Orthopaedic Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Department of Orthopaedic Surgery, Johns Hopkins Medicine, Baltimore, MD, USA.
J Bone Oncol. 2023 Oct 14;43:100507. doi: 10.1016/j.jbo.2023.100507. eCollection 2023 Dec.
Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy.
Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively.
The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35-44 (HR 1.27 [95 % CI 1.08-1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71-1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39-2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13-1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66-0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77-16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15-0.87, all p < 0.001).
The utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy.
抗吸收疗法常用于减轻和预防转移性骨病患者的骨相关事件。然而,关于抗吸收药物处方的发生率或相关因素,以及它们对骨转移性疾病患者病理性骨折发生率的影响,现有数据有限。本研究的目的是确定:1)骨转移患者在新诊断后2年内接受抗吸收治疗并发生病理性骨折的比例;2)与发生病理性骨折相关的因素;3)与接受抗吸收治疗可能性相关的因素。
在2010年1月至2021年10月期间,PearlDiver数据库的Mariner数据集中记录了1,492,301例新诊断为骨转移的患者。使用国际疾病分类(ICD)10编码识别骨转移患者。我们排除了先前诊断为骨转移的患者以及随访时间少于两年的患者。共有696,459例患者(46.7%)纳入分析。在这些患者中,63%(N = 437,716)年龄超过65岁,46%为女性,5.6%拥有医疗补助保险。我们确定了在新诊断为骨转移后2年内接受抗吸收治疗的患者。创建Cox比例风险模型,分别预测与1)病理性骨折和2)在新诊断为骨转移后2年内接受抗吸收治疗相关的因素。
我们队列中抗吸收治疗处方的发生率为7.7%。新诊断后2年内病理性骨折的发生率为7.3%。35 - 44岁患者(HR 1.27 [95% CI 1.08 - 1.51];p = 0.004)、原发性肾癌患者(HR 1.78 [95% CI 1.71 - 1.85];p < 0.001)、p = 0.005)、多发性骨髓瘤患者(HR 2.49 [95% CI 2.39 - 2.59];p < 0.001)和拥有医疗补助保险的患者(HR 1.17 [95% CI 1.13 - 1.21];p < 0.001)发生病理性骨折的风险更高。接受抗吸收治疗的患者发生病理性骨折的风险较低(HR 0.71 [95% CI 0.66 - 0.83];p < 0.001)。年龄增加是抗吸收治疗处方的独立预测因素(HR 1.77 - 16.38,所有p < 0.05)。男性以及原发性前列腺癌、肺癌或肾癌的诊断和医疗补助保险是抗吸收处方的负性预测因素(HR 0.15 - 0.87,所有p < 0.001)。
骨转移患者中抗吸收治疗的使用率仍然低得令人无法接受,尽管抗吸收治疗在降低病理性骨折发生率方面已显示出疗效,但只有7.7%的患者接受了这些治疗。本研究确定年轻患者、男性以及诊断为原发性前列腺癌、肾癌和肺癌的患者未接受抗吸收治疗的风险增加,这表明处方模式可能存在偏差。照顾这一弱势群体的医疗服务提供者需要做出更大努力,以提高抗吸收治疗的使用率并减少处方差异。