Keywords
fracture nonunion
osteosynthesis
patient-dependent risk factors
How to Cite
Abstract
Background. Delayed consolidation and nonunion after long bone fractures remain among the most severe complications in the surgical treatment of musculoskeletal injuries.
Objective. The study aims to determine the impact of patient-dependent risk factors for nonunion of long bone fractures after metal osteosynthesis and to rank these factors depending on fracture location.
Materials and Methods. A total of 165 patients who underwent metal osteosynthesis for long bone fractures (64 females and 101 males) and were treated for impaired reparative osteogenesis and nonunion were evaluated. The systematization of cases of nonunion of fractures was carried out according to the Weber-Cech classification. Patient-dependent factors (patient’s age, gender, smoking, alcohol abuse, overweight, use of nonsteroidal anti-inflammatory drugs, comorbidity) were studied.
Results and Discussion. The incidence of nonunion was higher in males than in females. The oligoplastic type of nonunion was more common than other types of impaired bone healing. A higher incidence of aplastic nonunion of humeral fractures was observed in females; for the lower extremities, oligoplastic nonunion most often occurred in males. Hyperplastic nonunion predominated exclusively in the group of segments of the lower extremities. Statistical analysis of risk factors for nonunion demonstrates a strong influence of smoking and the use of nonsteroidal anti-inflammatory drugs.
Conclusions. Smoking and the use of nonsteroidal anti-inflammatory drugs are the key factors influencing nonunion formation in long bone fractures. The distribution of prognostic factors for the formation of a false joint by morphological features demonstrates a homogeneous trend of ranking in the following areas: nonsteroidal anti-inflammatory drugs, age, smoking, gender, comorbidity, and alcohol consumption. The identification and ranking of these factors will allow for accurate clinical profiling of patients with long bone nonunion and for assessing the prognostic impact of these factors in individual clinical cases.
References
Hak DJ, Fitzpatrick D, Bishop JA, Marsh JL, Tilp S, Schnettler R, et al. Delayed union and nonunions: epidemiology, clinical issues, and financial aspects. Injury. 2014;45(Suppl 2):S3–7. doi:10.1016/j.injury.2014.04.002.
Antonova E, Le TK, Burge R, Mershon J. Tibia shaft fractures: costly burden of nonunions. BMC Musculoskelet Disord. 2013;14:42. doi:10.1186/1471-2474-14-42.
Mills LA, Aitken SA, Simpson AHRW. The risk of non-union per fracture: current myths and revised figures from a population of 4 million adults. Acta Orthop. 2017;88:434–9. doi:10.1080/17453674.2017.1321351.
Zura R, Xiong Z, Einhorn T, Watson JT, Ostrum RF, Prayson MJ, et al. Epidemiology of fracture nonunion in 18 human bones. JAMA Surg. 2016;151:e162775. doi:10.1001/jamasurg.2016.2775.
Mills L, Tsang J, Hopper G, Keenan G, Simpson AH. The multifactorial etiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res. 2016;5:512–9. doi:10.1302/2046-3758.510.BJR-2016-0138.
Ekegren CL, Edwards ER, de Steiger R, Gabbe BJ. Incidence, costs and predictors of non-union, delayed union and mal-union following long bone fracture. Int J Environ Res Public Health. 2018;15:2845. doi:10.3390/ijerph15122845.
Jensen SS, Jensen NM, Gundtoft PH, Kold S, Zura R, Viberg B. Risk factors for nonunion following surgically managed, traumatic, diaphyseal fractures: a systematic review and meta-analysis. EFORT Open Rev. 2022;7(7):516–25. doi:10.1530/EOR-21-0137.
Santolini E, West RM, Giannoudis PV. Leeds–Genoa Non-Union Index: a clinical tool for assessing the need for early intervention after long bone fracture fixation. Int Orthop. 2020;44:161–72. doi:10.1007/s00264-019-04376-0.
Gaddi D, Gatti SD, Piatti M, Poli A, De Rosa L, Riganti A, et al. Non-Union Scoring System (NUSS): is it enough in clinical practice? Indian J Orthop. 2023;57:137–45.
O’Halloran K, Coale M, Costales T, Zerhusen T, Castillo RC, O’Toole RV. Will my tibial fracture heal? Predicting nonunion at the time of definitive fixation based on commonly available variables. Clin Orthop Relat Res. 2016;474:1385–95. doi:10.1007/s11999-016-4821-4.
Massari L, Benazzo F, Falez F, Cadossi R, Perugia D, Pietrogrande L, et al. Can clinical and surgical parameters be combined to predict how long it will take a tibia fracture to heal? A prospective multicentre observational study: the FRACTING study. Biomed Res Int. 2018;2018:1809091. doi:10.1155/2018/1809091.
Chloros GD, Kanakaris NK, Vun JSH, Howard A, Giannoudis PV. Scoring systems for early prediction of tibial fracture non-union: an update. Int Orthop. 2021;45:2081–91. doi:10.1007/s00264-021-05088-0.
Makaram NS, Leow JM, Clement ND, Oliver WM, Ng ZH, Simpson C, et al. Risk factors associated with delayed and aseptic nonunion following tibial diaphyseal fractures managed with intramedullary nailing. Bone Jt Open. 2021;2(4):227–35. doi:10.1302/2633-1462.24.BJO-2021-0012.R1.
Wittauer M, Burch MA, McNally M, Vandendriessche T, Clauss M, Della Rocca GJ, et al. Definition of long-bone nonunion: a scoping review of prospective clinical trials to evaluate current practice. Injury. 2021;52:3200–5. doi:10.1016/j.injury.2021.09.008.
Quarta D, Grassi M, Lattanzi G, Gigante AP, D’Anca A, Potena D. Three predictive scores compared in a retrospective multicenter study of nonunion tibial shaft fracture. World J Orthop. 2024;15(6):560–9. doi:10.5312/wjo.v15.i6.560.
Andrzejowski P, Giannoudis PV. The ‘diamond concept’ for long bone non-union management. J Orthop Traumatol. 2019;20:21. doi:10.1186/s10195-019-0528-0.
Nandra R, Grover L, Porter K. Fracture non-union epidemiology and treatment. Trauma. 2015;18:3–11.
Weber BG, Cech O. Pseudarthrosis. New York: Grune & Stratton; 1976. 323 p.
Chitnis AS, Vanderkarr M, Sparks C, McGlohorn J, Holy CE. Complications and its impact in patients with closed and open tibial shaft fractures requiring open reduction and internal fixation. J Comp Eff Res. 2019;8:1405–16. doi:10.2217/cer-2019-0108.
Ding L, He Z, Xiao H, Chai L, Xue F. Factors affecting the incidence of aseptic nonunion after surgical fixation of humeral diaphyseal fracture. J Orthop Sci. 2014;19:973–7. doi:10.1007/s00776-014-0640-1.
Lack WD, Starman JS, Seymour R, Bosse M, Karunakar M, Sims S, et al. Any cortical bridging predicts healing of tibial shaft fractures. J Bone Joint Surg Am. 2014;96:1066–72. doi:10.2106/JBJS.M.00385.
Metsemakers WJ, Handojo K, Reynders P, Sermon A, Vanderschot P, Nijs S. Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients. Injury. 2015;46:740–5. doi:10.1016/j.injury.2014.12.018.
Wu CL, Chang HC, Lu KH. Risk factors for nonunion in 337 displaced midshaft clavicular fractures treated with Knowles pin fixation. Arch Orthop Trauma Surg. 2013;133:15–22. doi:10.1007/s00402-012-1631-3.
Wu KJ, Li SH, Yeh KT, Chen IH, Lee RP, Yu TC, et al. The risk factors of nonunion after intramedullary nailing fixation of femur shaft fracture in middle-aged patients. Medicine (Baltimore). 2019;98:e16559. doi:10.1097/MD.0000000000016559.
Metsemakers WJ, Roels N, Belmans A, Reynders P, Nijs S. Risk factors for nonunion after intramedullary nailing of femoral shaft fractures: remaining controversies. Injury. 2015;46:1601–7. doi:10.1016/j.injury.2015.05.007.
Donohue D, Sanders D, Serrano-Riera R, Jordan C, Gaskins R, Sanders R, et al. Ketorolac administered in the recovery room for acute pain management does not affect healing rates of femoral and tibial fractures. J Orthop Trauma. 2016;30:479–82. doi:10.1097/BOT.0000000000000620.
Thakore RV, Francois EL, Nwosu SK, Attum B, Whiting PS, Siuta MA, et al. The Gustilo–Anderson classification system as predictor of nonunion and infection in open tibia fractures. Eur J Trauma Emerg Surg. 2017;43:651–6. doi:10.1007/s00068-016-0725-y.
Niikura T, Lee SY, Sakai Y, Nishida K, Kuroda R, Kurosaka M. Causative factors of fracture nonunion: the proportions of mechanical, biological, patient-dependent, and patient-independent factors. J Orthop Sci. 2014;19:120–4. doi:10.1007/s00776-013-0472-4.
Zaghloul A, Haddad B, Barksfield R, Davis B. Early complications of surgery in operative treatment of ankle fractures in those over 60: a review of 186 cases. Injury. 2014;45:780–3. doi:10.1016/j.injury.2013.11.008.
Terer E, Ayumba B, Kisorio J. Outcomes of operative management of humerus fracture nonunion among adults. Int J Sci Res Publ. 2024;14(5). doi:10.29322/IJSRP.14.05.2024.p1490.
Dimartino S, Pavone V, Carnazza M, Cuffaro ER, Sergi F, Testa G. Forearm fracture nonunion with and without bone loss: an overview of adult and child populations. J Clin Med. 2022;11(14):4106. doi:10.3390/jcm11144106.
Boussakri H, Elibrahimi A, Bachiri M, Elidrissi M, Shimi M, Malays EA. Nonunion of fractures of the ulna and radius diaphyses: clinical and radiological results of surgical treatment. MOJ Orthop Rheumatol. 2016;10(2):27–34. doi:10.5704/MOJ.1607.006.
Kraus KR, Flores JW, Slaven JE, Sharma I, Arnold PK, Mullis BH, et al. A scoring system for predicting nonunion after intramedullary nailing of femoral shaft fractures. JAAOS Glob Res Rev. 2024;8(9):e24.00214. doi:10.5435/JAAOSGlobal-D-24-00214.
Ma YG, Hu GL, Hu W, Liang F. Surgical factors contributing to nonunion in femoral shaft fracture following intramedullary nailing. Chin J Traumatol. 2016;19:109–12. doi:10.1016/j.cjtee.2016.01.012.
Metsemakers WJ, Roels N, Belmans A, Reynders P, Nijs S. Risk factors for nonunion after intramedullary nailing of femoral shaft fractures: remaining controversies. Injury. 2015;46:1601–7. doi:10.1016/j.injury.2015.05.007.
Millar MJ, Wilkinson A, Navarre P, Steiner J, Vohora A, Hardidge A, et al. Nail fit: does nail diameter to canal ratio predict the need for exchange nailing in the setting of aseptic, hypertrophic femoral nonunions? J Orthop Trauma. 2018;32:245–50. doi:10.1097/BOT.0000000000001110.
Alam MA, Shirazi AF, Alaradi H. Association of fracture location and pattern with nonunion or malunion in tibia fractures managed with intramedullary nailing: a retrospective study. Cureus. 2023;15(11):e49156. doi:10.7759/cureus.49156.
White AE, Henry JK, Dziadosz D. The effect of nonsteroidal antiinflammatory drugs and selective COX-2 inhibitors on bone healing. HSS J. 2021;17(2):231–4. doi:10.1177/1556331621998634.
George MD, Baker JF, Leonard CE, Mehta S, Miano TA, Hennessy S. Risk of nonunion with nonselective NSAIDs, COX-2 inhibitors, and opioids. J Bone Joint Surg Am. 2020;102(14):1230–8. doi:10.2106/JBJS.19.01415.
Ehnert S, Relja B, Schmidt-Bleek K, Fischer V, Ignatius A, Linnemann C, et al. Effects of immune cells on mesenchymal stem cells during fracture healing. World J Stem Cells. 2021;13(11):1667–95. doi:10.4252/wjsc.v13.i11.1667.
Ono T, Takayanagi H. Osteoimmunology in bone fracture healing. Curr Osteoporos Rep. 2017;15(4):367–75. doi:10.1007/s11914-017-0381-0.
Lisowska B, Kosson D, Domaracka K. Lights and shadows of NSAIDs in bone healing: the role of prostaglandins in bone metabolism. Drug Des Devel Ther. 2018;12:1753–8. doi:10.2147/DDDT.S164562.
Boursinos LA, Karachalios T, Poultsides L, Malizos KN. Do steroids, conventional non-steroidal anti-inflammatory drugs and selective COX-2 inhibitors adversely affect fracture healing? J Musculoskelet Neuronal Interact. 2009;9(1):44–52.
Pountos I, Panteli M, Walters G, Giannoudis PV. NSAIDs inhibit bone healing through the downregulation of TGF-β3 expression during endochondral ossification. Injury. 2021;52(6):1294–9. doi:10.1016/j.injury.2021.01.007.
Janssen MP, Caron MM, van Rietbergen B, Surtel DA, van Rhijn LW, Welting TJ, et al. Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase. Eur Cell Mater. 2017;34:202–16. doi:10.22203/eCM.v034a13.
Al-Waeli H, Reboucas AP, Mansour A, Morris M, Tamimi F, Nicolau B. Non-steroidal anti-inflammatory drugs and bone healing in animal models: a systematic review and meta-analysis. Syst Rev. 2021;10(1):201. doi:10.1186/s13643-021-01690-w.
Al Farii H, Farahdel L, Frazer A, Salimi A, Bernstein M. The effect of NSAIDs on postfracture bone healing: a meta-analysis of randomized controlled trials. OTA Int. 2021;4(2):e092. doi:10.1097/OI9.0000000000000092.
Wheatley BM, Nappo KE, Christensen DL, Holman AM, Brooks DI, Potter BK. Effect of NSAIDs on bone healing rates: a meta-analysis. J Am Acad Orthop Surg. 2019;27(7):e330–6. doi:10.5435/JAAOS-D-17-00727.
Tucker WA, Birt MC, Heddings AA, Horton GA. The effect of postoperative nonsteroidal anti-inflammatory drugs on nonunion rates in long bone fractures. Orthopedics. 2020;43(4):221–7. doi:10.3928/01477447-20200428-06.
Quan K, Xu Q, Zhu M, Liu X, Dai M. Analysis of risk factors for non-union after surgery for limb fractures: a case-control study of 669 subjects. Front Surg. 2021;8:754150. doi:10.3389/fsurg.2021.754150.
Nuelle JAV, Coe KM, Oliver HA, Cook JL, Hoernschemeyer DG, Gupta SK. Effect of NSAID use on bone healing in pediatric fractures: a preliminary, prospective, randomized, blinded study. J Pediatr Orthop. 2020;40(8):e683–9. doi:10.1097/BPO.0000000000001603.
Barnds B, Heenan M, Ayres J, Tarakemeh A, Schroeppel JP, Mullen S, et al. Comparison of the rate of delayed/nonunion in fifth metatarsal fractures receiving anti-inflammatory medications. J Exp Orthop. 2021;8(1):115. doi:10.1186/s40634-021-00435-x.
This work is licensed under a Creative Commons Attribution 4.0 International License.