Long-term use of opioids and neuropathic medication after diaphyseal humerus fractures with or without nerve injury: a nationwide register-based cohort study of 4,185 patients
DOI:
https://doi.org/10.2340/17453674.2026.46808Keywords:
humerus fractures, nerve injury, neuropathic pain medication, opioids, pain, socioeconomic factorsAbstract
Background and purpose: Diaphyseal humerus fractures may lead to prolonged pain medication use. We aimed to study pain medication use after such fractures, focusing on nerve injury.
Methods: Using Swedish register data (2007–2015), we identified individuals with diaphyseal humerus fractures. High use of opioids and neuropathic pain medication (≥ 60% of days covered/year; 2-month post-fracture washout) was evaluated in 5 groups: the general population (reference) and fractures treated nonoperatively or surgically, with and without nerve injury. Relative risks (RRs; 95% confidence intervals [CIs]; crude and adjusted [aRR] models; adjusted for age, sex, country of birth, income, and cohabitation status; and for previous high use of pain medication during the first year when analyzing the second year) were estimated in Cox proportional hazards regression models.
Results: We identified 4,185 individuals with diaphyseal humerus fractures (3.7% with nerve injury; 23% surgically treated). In the first year, opioid use was higher among surgically treated fractures with nerve injury (aRR 17.6, CI 11.0–28.3) and without nerve injury (aRR 9.5, CI 8.2–10.9) than in the general population. In the second year, opioid use declined across most groups but remained elevated among nonoperatively treated fractures with nerve injury (aRR 8.3, CI 2.6–26.1). Neuropathic pain medication use increased in the first year, with no elevated use in the second. Adjustment did not change overall patterns. Women, older adults, lower-income individuals, and those living alone showed higher medication risk use.
Conclusion: Patients with a diaphyseal humerus fracture were associated with a substantial burden of pain medication use, particularly for opioids during the first year post-injury in surgically treated fractures with nerve injury (RR 17.6) and a persistent risk in the second year among nonoperatively treated fractures with nerve injury (RR 8.3). Demographics and socioeconomic factors strongly relate to medication use, highlighting the need for careful early pain management and monitoring for prolonged medication use in exposed groups.
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References
Belayneh R, Lott A, Haglin J, Konda S, Leucht P, Egol K. Final outcomes of radial nerve palsy associated with humeral shaft fracture and nonunion. J Orthop Traumatol 2019; 20: 18. doi: 10.1186/s10195-019-0526-2. DOI: https://doi.org/10.1186/s10195-019-0526-2
Daly M, Langhammer C. Radial nerve injury in humeral shaft fracture. Orthop Clin North Am 2022; 53: 145-54. doi: 10.1016/j.ocl.2022.01.001. DOI: https://doi.org/10.1016/j.ocl.2022.01.001
Ekholm R, Adami J, Tidermark J, Hansson K, Tornkvist H, Ponzer S. Fractures of the shaft of the humerus: an epidemiological study of 401 fractures. J Bone Joint Surg Br 2006; 88: 1469-73. doi: 10.1302/0301-620X.88B11.17634. DOI: https://doi.org/10.1302/0301-620X.88B11.17634
Oliver W M, Bell K R, Carter T H, Graham C, White T O, Clement N D, et al. Operative vs nonoperative management of fractures of the humeral diaphysis: the Humeral Shaft Fracture Fixation Randomized Clinical Trial. JAMA Surg 2025; 160: 508-16. doi: 10.1001/jamasurg.2025.0301. DOI: https://doi.org/10.1001/jamasurg.2025.0301
Ibounig T, Wolf O, Oliver W M, Karimi D, Viberg B, Ratasvuori M, et al. An Acta Orthopaedica educational article: Treatment of adult patients with a humeral shaft fracture. Acta Orthop 2026; 97: 194-203. doi: 10.2340/17453674.2026.45597. DOI: https://doi.org/10.2340/17453674.2026.45597
Karimi D, Qvistgaard S W, Gundtoft P H, Brorson S, Viberg B. Unchanged incidence but change in treatment trends from 1996 to 2018: 23,718 humeral shaft fractures from the Danish National Patient Registry. Acta Orthop 2023; 94: 523-9. doi: 10.2340/17453674.2023.21125. DOI: https://doi.org/10.2340/17453674.2023.21125
Beyer J, Rao B, Liu J, Skie M. Evaluation of humeral shaft fracture outcomes by treatment method: a systematic review and meta-analysis based on comparison studies. JBJS Rev 2023; 11. doi: 10.2106/JBJS.RVW.23.00037. DOI: https://doi.org/10.2106/JBJS.RVW.23.00037
Updegrove G F, Mourad W, Abboud J A. Humeral shaft fractures. J Shoulder Elbow Surg 2018; 27: e87-e97. doi: 10.1016/j.jse.2017.10.028. DOI: https://doi.org/10.1016/j.jse.2017.10.028
Ramo L, Taimela S, Lepola V, Malmivaara A, Lahdeoja T, Paavola M. Open reduction and internal fixation of humeral shaft fractures versus conservative treatment with a functional brace: a study protocol of a randomised controlled trial embedded in a cohort. BMJ Open 2017; 7: e014076. doi: 10.1136/bmjopen-2016-014076. DOI: https://doi.org/10.1136/bmjopen-2016-014076
Hendrickx L A M, Hilgersom N F J, Alkaduhimi H, Doornberg J N, van den Bekerom M P J. Radial nerve palsy associated with closed humeral shaft fractures: a systematic review of 1758 patients. Arch Orthop Trauma Surg 2021; 141: 561-8. doi: 10.1007/s00402-020-03446-y. DOI: https://doi.org/10.1007/s00402-020-03446-y
Ilyas A M, Mangan J J, Graham J. Radial nerve palsy recovery with fractures of the humerus: an updated systematic review. J Am Acad Orthop Surg 2020; 28: e263-e269. doi: 10.5435/JAAOS-D-18-00142. DOI: https://doi.org/10.5435/JAAOS-D-18-00142
Shao Y C, Harwood P, Grotz M R, Limb D, Giannoudis P V. Radial nerve palsy associated with fractures of the shaft of the humerus: a systematic review. J Bone Joint Surg Br 2005; 87: 1647-52. doi: 10.1302/0301-620X.87B12.16132. DOI: https://doi.org/10.1302/0301-620X.87B12.16132
Hegeman E M, Polmear M, Scanaliato J P, Nesti L, Dunn J C. Incidence and management of radial nerve palsies in humeral shaft fractures: a systematic review. Cureus 2020; 12: e11490. doi: 10.7759/cureus.11490. DOI: https://doi.org/10.7759/cureus.11490
Ortega-Yago A, Ferras-Tarrago J, Jover-Jorge N, Baixauli-Garcia F. Radial nerve paralysis in diaphyseal fractures of the humerus. Plast Aesthet Nurs (Phila) 2022; 42: 156-62. doi: 10.1097/PSN.0000000000000442. DOI: https://doi.org/10.1097/PSN.0000000000000442
Novak C B, Anastakis D J, Beaton DE, Mackinnon S E, Katz J. Relationships among pain disability, pain intensity, illness intrusiveness, and upper extremity disability in patients with traumatic peripheral nerve injury. J Hand Surg Am 2010; 35: 1633-9. doi: 10.1016/j.jhsa.2010.07.018. DOI: https://doi.org/10.1016/j.jhsa.2010.07.018
Ludvigsson J F, Andersson E, Ekbom A, Feychting M, Kim J L, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health 2011; 11: 450. doi: 10.1186/1471-2458-11-450. DOI: https://doi.org/10.1186/1471-2458-11-450
Wettermark B, Hammar N, Fored C M, Leimanis A, Otterblad Olausson P, Bergman U, et al. The new Swedish Prescribed Drug Register: opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 2007; 16: 726-35. doi: 10.1002/pds.1294. DOI: https://doi.org/10.1002/pds.1294
Ludvigsson J F, Svedberg P, Olen O, Bruze G, Neovius M. The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research. Eur J Epidemiol 2019; 34: 423-37. doi: 10.1007/s10654-019-00511-8. DOI: https://doi.org/10.1007/s10654-019-00511-8
Ludvigsson J F, Almqvist C, Bonamy A K, Ljung R, Michaelsson K, Neovius M, et al. Registers of the Swedish total population and their use in medical research. Eur J Epidemiol 2016; 31: 125-36. doi: 10.1007/s10654-016-0117-y. DOI: https://doi.org/10.1007/s10654-016-0117-y
Bergdahl C, Nilsson F, Wennergren D, Ekholm C, Moller M. Completeness in the Swedish Fracture Register and the Swedish National Patient Register: an assessment of humeral fracture registrations. Clin Epidemiol 2021; 13: 325-33. doi: 10.2147/CLEP.S307762. DOI: https://doi.org/10.2147/CLEP.S307762
Lewer D, Brothers T, O’Nions E, Pickavance J. Factors associated with: problems of using exploratory multivariable regression to identify causal risk factors. BMJ Med 2025; 4: e001375. doi: 10.1136/bmjmed-2025-001375. DOI: https://doi.org/10.1136/bmjmed-2025-001375
Entezari V, Olson J J, Vallier H A. Predictors of traumatic nerve injury and nerve recovery following humeral shaft fracture. J Shoulder Elbow Surg 2021; 30: 2711-9. doi: 10.1016/j.jse.2021.04.025. DOI: https://doi.org/10.1016/j.jse.2021.04.025
Swedish Fracture Register (SFR). Registercentrum Västra Götaland, Göteborg, Sweden; 2026 [cited 2026 January 17]. Available from: https://sfr.registercentrum.se/in-english/the-swedish-fracture-register/p/HyEtC7VJ4
Chou R, Turner J A, Devine E B, Hansen R N, Sullivan S D, Blazina I, et al. The effectiveness and risks of long-term opioid therapy for chronic paIn: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015; 162: 276-86. doi: 10.7326/M14-2559. DOI: https://doi.org/10.7326/M14-2559
Cunningham D J, LaRose M A, Anakwenze O A, Klifto C S, Richard M J, Ruch D S, et al. Fracture location impacts opioid demand in upper extremity fracture surgery. Injury 2021; 52: 2314-21. doi: 10.1016/j.injury.2021.05.026. DOI: https://doi.org/10.1016/j.injury.2021.05.026
Hah J M, Bateman B T, Ratliff J, Curtin C, Sun E. Chronic opioid use after surgery: implications for perioperative management in the face of the opioid epidemic. Anesth Analg 2017; 125: 1733-40. doi: 10.1213/ANE.0000000000002458. DOI: https://doi.org/10.1213/ANE.0000000000002458
Lawal O D, Gold J, Murthy A, Ruchi R, Bavry E, Hume A L, et al. Rate and risk factors associated with prolonged opioid use after surgery: a systematic review and meta-analysis. JAMA Netw Open 2020; 3: e207367. doi: 10.1001/jamanetworkopen.2020.7367. DOI: https://doi.org/10.1001/jamanetworkopen.2020.7367
Waljee J F, Zhong L, Hou H, Sears E, Brummett C, Chung K C. The use of opioid analgesics following common upper extremity surgical procedures: a national, population-based study. Plast Reconstr Surg 2016; 137: 355e-364e. doi: 10.1097/01.prs.0000475788.52446.7b. DOI: https://doi.org/10.1097/01.prs.0000475788.52446.7b
Fischer M R, Abbott A, Bjork M, Jansen G B, Goran G, Stalnacke B M, et al. An action plan: the Swedish healthcare pathway for adults with chronic pain. Scand J Pain 2025; 25. doi: 10.1515/sjpain-2024-0082. DOI: https://doi.org/10.1515/sjpain-2024-0082
Moisset X, Bouhassira D, Attal N. French guidelines for neuropathic paIn: an update and commentary. Rev Neurol (Paris) 2021; 177: 834-7. doi: 10.1016/j.neurol.2021.07.004. DOI: https://doi.org/10.1016/j.neurol.2021.07.004
Jayawardana S, Forman R, Johnston-Webber C, Campbell A, Berterame S, de Joncheere C, et al. Global consumption of prescription opioid analgesics between 2009–2019: a country-level observational study. EClinicalMedicine 2021; 42: 101198. doi: 10.1016/j.eclinm.2021.101198. DOI: https://doi.org/10.1016/j.eclinm.2021.101198
Läkemedelsverket. Förskrivning av opioider i Sverige Läkemedel, doser och diagnoser; 2020 [cited 2026 Jan 17]. Available from: https://www.lakemedelsverket.se/sv/om-lakemedelsverket/rapporter-och-publikationer/narkotika/forskrivning-av-opioider-i-sverige---lakemedel-doser-och-diagnoser#hmainbody1
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