Long-term clonidine and fracture risk in children with attention-deficit hyperactivity disorder: multicentre electronic health record evidence
DOI:
https://doi.org/10.18203/issn.2455-4510.IntJResOrthop20262016Keywords:
Clonidine, ADHD, Pediatric fractures, Distal radius, Supracondylar humerusAbstract
Background: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) experience elevated injury rates. Clonidine is commonly prescribed for ADHD, yet its association with fracture risk has not been well defined.
Methods: Retrospective study using TriNetX. Patients (6-18 years) with ADHD (ICD-10-CM F90) were classified as clonidine-exposed if they had a prescription within 6 months before or on the ADHD index date; controls had no clonidine exposure. Matching yielded 73,141 patients per cohort. Follow-up began 1 day after the index and extended through available records, up to 20 years. Primary outcomes were distal radius (S52.5), clavicle (S42.0), and supracondylar humerus (S42.41) fractures.
Results: After matching, 133,630 patients were included (66,815 per cohort). Thirty-day postoperative infection occurred in 1.03% (690/66,815) of SSRI users versus 1.44% (963/66,815) of non-SSRI controls (risk difference-0.41 percentage points; RR 0.71, 95% CI 0.64-0.78; HR 0.69, 95% CI 0.62-0.76; p<0.001). No statistically significant differences were observed for delayed wound healing, wound dehiscence, hematoma, seroma, nausea, or sepsis.
Conclusions: Clonidine exposure was associated with lower risks of distal radius, clavicle, and supracondylar humerus fractures. Findings support prospective studies to confirm causality and explore mechanisms.
Metrics
References
Thomas R, Sanders S, Doust J, Beller E, Glasziou P. Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics. 2015;135(4):e994-1001. DOI: https://doi.org/10.1542/peds.2014-3482
Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2015;1:15020. DOI: https://doi.org/10.1038/nrdp.2015.20
Arnsten AF. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 2010;10(10):1595-605. DOI: https://doi.org/10.1586/ern.10.133
Bello NT. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents. Patient Prefer Adherence. 2015;9:877-85. DOI: https://doi.org/10.2147/PPA.S73167
Palumbo DR, Sallee FR, Pelham WE, Bukstein OG, Daviss WB, McDERMOTT MP. Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47(2):180-8. DOI: https://doi.org/10.1097/chi.0b013e31815d9af7
Ruiz-Goikoetxea M, Cortese S, Aznarez-Sanado M, Magallón S, Alvarez Zallo N, Luis EO, et al. Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2018;84:63-71. DOI: https://doi.org/10.1016/j.neubiorev.2017.11.007
Zhang SW, Shen D, Yan YT. ADHD, stimulant medication use, and the risk of fracture: a systematic review and meta-analysis. Arch Osteoporos. 2021;16(1):81. DOI: https://doi.org/10.1007/s11657-021-00960-3
Khosla S, Melton LJ, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL. Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA. 2003;290(11):1479-85. DOI: https://doi.org/10.1001/jama.290.11.1479
Arnsten AF. Catecholamine influences on dorsolateral prefrontal cortical networks. Biol Psychiatry. 2011;69(12):e89-99. DOI: https://doi.org/10.1016/j.biopsych.2011.01.027
Milewski MD, Skaggs DL, Bishop GA, Pace JL, Ibrahim DA, Wren TA, et al. Chronic lack of sleep is associated with increased sports injuries in adolescent athletes. J Pediatr Orthop. 2014;34(2):129-33. DOI: https://doi.org/10.1097/BPO.0000000000000151
Randsborg PH, Gulbrandsen P, Saltytė Benth J, Sivertsen EA, Hammer OL, Fuglesang HF, et al. Fractures in children: epidemiology and activity-specific fracture rates. J Bone Joint Surg Am. 2013;95(7):e42. DOI: https://doi.org/10.2106/JBJS.L.00369
Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399-424. DOI: https://doi.org/10.1080/00273171.2011.568786
Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885. DOI: https://doi.org/10.1371/journal.pmed.1001885
Hazell PL, Stuart JE. A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. J Am Acad Child Adolesc Psychiatry. 2003;42(8):886-94. DOI: https://doi.org/10.1097/01.CHI.0000046908.27264.00
Man KK, Chan EW, Coghill D, Douglas I, Ip P, Leung LP, et al. Methylphenidate and the risk of trauma. Pediatrics. 2015;135(1):40-8. DOI: https://doi.org/10.1542/peds.2014-1738
Hernán MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol. 2016;183(8):758-64. DOI: https://doi.org/10.1093/aje/kwv254
Soligard T, Myklebust G, Steffen K, Holme I, Silvers H, Bizzini M, et al. Comprehensive warm-up programme to prevent injuries in young female footballers: cluster randomised controlled trial. BMJ. 2008;337:a2469. DOI: https://doi.org/10.1136/bmj.a2469
Downloads
Published
How to Cite
Issue
Section
