Thomas Buchheit1, Robert Zura2, Zhe Wang3, Samir Mehta4, Gregory J Della Rocca5, R Grant Steen6. 1. Dept. of Anesthesiology, Duke University Medical Center, Durham, NC, United States. Electronic address: thomas.buchheit@duke.edu. 2. Dept. of Orthopaedic Surgery, Louisiana State University Medical Center, New Orleans, LA, United States. Electronic address: rzura@lsuhsc.edu. 3. Dept. of Statistics, North Carolina State University, Raleigh, NC, United States. Electronic address: zwang28@ncsu.edu. 4. Dept. of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. Electronic address: Samir.Mehta@uphs.upenn.edu. 5. Dept. of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, United States. Electronic address: gregory.della.rocca@duke.edu. 6. Dept. of Orthopaedic Surgery, Louisiana State University Medical Center, New Orleans, LA, United States. Electronic address: Grant.Steen@bioventusglobal.com.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSIONS: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, traumapatients 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.
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