Dept. of Anesthesiology, Duke University Medical Center, Durham, NC, United States.
Dept. of Orthopaedic Surgery, Louisiana State University Medical Center, New Orleans, LA, United States.
Injury. 2018 Jul;49(7):1266-1271. doi: 10.1016/j.injury.2018.05.004. Epub 2018 May 21.
Certain common medications are associated with an elevated risk of fracture and recent data suggests that medications can also increase nonunion risk. Medication use is a modifiable nonunion risk factor, but it is unknown whether risk accrues solely to chronic medication use or whether there is also risk inherent to acute use.
Multivariate logistic regression was used in an inception cohort to calculate odds ratios (OR) for fracture nonunion associated with medication use, in context with other risk factors demonstrated to influence nonunion. Patient-level health claims for medical and drug expenses were compiled from a payer database. Patients were included if they had a fracture coded in 2011, with continuous enrollment for 1 month prior to and 12 months after fracture. The database contained demographic descriptors, treatment procedures per CPT codes, co-morbidities per ICD-9 codes, and prescriptions per National Drug Codes. Chronic medication use was defined as ≥30 days of prescription prior to fracture with ≥1 day afterward; acute use was any other prescription.
Most non-analgesic medications were safe in acute or chronic use, but risk of nonunion was elevated for a wide range of analgesics. Overall, 45,085 fractures (14.6% of fractures) affected patients using chronic opioids. Nonunion OR was elevated for acute and chronic use of Schedule 2 opioids including acetaminophen/oxycodone, hydromorphone, oxycodone, and acetaminophen/hydrocodone bitartrate, as well as Schedule 3-5 opioids including tramadol (all, p < 0.0001). The highest ORs were associated with chronic administration of Schedule 2 opioids.
Most medications do not increase nonunion risk, but acute and chronic use of NSAIDs or opioids was associated with impaired fracture healing. There is particular risk in prescribing opioid analgesics for fracture, though literature suggests that roughly half of opioid-naïve patients receive such a prescription.
Patients evaluated in this study were not a random sample of Americans; they may approximate a random sample of the Emergency Department population in the United States. Thus, trauma patients may represent a population enriched for nonunion risk factors. Opioids impair recovery from injury; if they also predispose to injury, the ongoing opioid epidemic could presage an increase in nonunion prevalence.
某些常见药物与骨折风险升高有关，最近的数据表明，药物也会增加骨折不愈合的风险。药物的使用是一个可以改变的骨折不愈合的风险因素，但尚不清楚这种风险仅归因于慢性药物使用，还是急性药物使用也存在固有风险。
在一个入组队列中使用多变量逻辑回归来计算与药物使用相关的骨折不愈合的比值比（OR），并结合其他已证明影响骨折不愈合的风险因素。从一个支付方数据库中编译了患者的医疗和药物费用的患者级健康索赔。如果患者在 2011 年有骨折编码，并在骨折前 1 个月和骨折后 12 个月连续入组，则将其纳入研究。该数据库包含人口统计学描述符、按 CPT 代码的治疗程序、按 ICD-9 代码的合并症以及按国家药物代码的处方。慢性药物使用定义为骨折前≥30 天的处方，且骨折后≥1 天仍在使用；急性使用是指其他任何处方。
大多数非镇痛药物在急性或慢性使用时是安全的，但广泛的镇痛药会增加骨折不愈合的风险。总体而言，45085 例骨折（占骨折的 14.6%）影响了使用慢性阿片类药物的患者。急性和慢性使用包括对乙酰氨基酚/羟考酮、氢吗啡酮、羟考酮和酒石酸氢可酮、以及曲马多在内的 2 类阿片类药物（所有药物，p<0.0001）的患者，骨折不愈合的 OR 升高。与慢性使用 2 类阿片类药物相关的 OR 最高。
大多数药物不会增加骨折不愈合的风险，但 NSAIDs 或阿片类药物的急性和慢性使用与骨折愈合受损有关。开处方治疗骨折的阿片类镇痛药存在特殊风险，尽管文献表明，大约一半的阿片类药物初治患者接受了此类处方。
本研究中评估的患者不是美国人的随机样本；他们可能接近美国急诊科人群的随机样本。因此，创伤患者可能代表骨折不愈合风险因素丰富的人群。阿片类药物会损害受伤后的恢复；如果它们也容易导致受伤，那么持续的阿片类药物流行可能预示着骨折不愈合的患病率增加。
