The Contributing Factors of Nonunion Bone Fractures: A Brief Review
Abstract
The skeletal system has a high healing capacity. A nonunion fracture occurs when the natural course of bone healing is impaired. Numerous local and systemic factors participate in the development of a nonunion fracture. Patients with diabetes mellitus (DM), smoking history, obesity, and malnutrition are at risk for nonunion. Moreover, the major local risk factors for impaired bone healing are malalignment, infection, mechanical stability, and tissue loss. In this brief review, we discuss the definition, epidemiology, and diagnosis of nonunion. We further explain the major contributing factors which must be considered in patient selection for nonunion revision surgeries.
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4. Einhorn TA, Gerstenfeld LC. Fracture healing: Mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45-54. doi: 10.1038/nrrheum.2014.164. [PubMed: 25266456]. [PubMed Central: PMC4464690].
5. Ekegren CL, Edwards ER, de SR, 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(12). doi: 10.3390/ijerph15122845. [PubMed: 30551632]. [PubMed Central: PMC6313538].
6. Wildemann B, Ignatius A, Leung F, Taitsman LA, Smith RM, Pesantez R, et al. Non-union bone fractures. Nat Rev Dis Primers. 2021;7(1):57. doi: 10.1038/s41572-021-00289-8. [PubMed: 34354083].
7. Bell A, Templeman D, Weinlein JC. Nonunion of the femur and tibia: An update. Orthop Clin North Am. 2016;47(2):365-75. doi: 10.1016/j.ocl.2015.09.010. [PubMed: 26772945].
8. 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(11):e162775. doi: 10.1001/jamasurg.2016.2775. [PubMed: 27603155].
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10. Mills LA, Aitken SA, Simpson AHRW. The risk of non-union per fracture: Current myths and revised figures from a population of over 4 million adults. Acta Orthop. 2017;88(4):434-9. doi: 10.1080/17453674.2017.1321351. [PubMed: 28508682]. [PubMed Central: PMC5499337].
11. Bhandari M, Fong K, Sprague S, Williams D, Petrisor B. Variability in the definition and perceived causes of delayed unions and nonunions: A cross-sectional, multinational survey of orthopaedic surgeons. J Bone Joint Surg Am. 2012;94(15): e1091-e1096. doi: 10.2106/JBJS.K.01344. [PubMed: 22854998].
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14. Bhandari M, Chiavaras M, Ayeni O, Chakraverrty R, Parasu N, Choudur H, et al. Assessment of radiographic fracture healing in patients with operatively treated femoral neck fractures. J Orthop Trauma. 2013;27(9):e213-e219. doi: 10.1097/BOT.0b013e318282e692. [PubMed: 23287749].
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18. Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R. Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab. 2009;27(5):555-61. doi: 10.1007/s00774-009-0075-5. [PubMed: 19436947].
19. Mousavi SE, Amini H, Heydarpour P, Amini CF, Godderis L. Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms. Environ Int. 2019;122:67-90. doi: 10.1016/j.envint.2018.11.052. [PubMed: 30509511].
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21. Cobb TK, Gabrielsen TA, Campbell DC, Wallrichs SL, Ilstrup DM. Cigarette smoking and nonunion after ankle arthrodesis. Foot Ankle Int. 1994;15(2):64-7. doi: 10.1177/107110079401500202. [PubMed: 7981802].
22. Silcox DH 3
, Daftari T, Boden SD, Schimandle JH, Hutton WC, Whitesides TE. The effect of nicotine on spinal fusion. Spine
(Phila Pa 1976). 1995;20(14):1549-53. doi: 10.1097/00007632-
199507150-00001. [PubMed: 7570168].
23. Andersen T, Christensen FB, Laursen M, Hoy K, Hansen ES, Bunger C. Smoking as a predictor of negative outcome in lumbar spinal fusion. Spine (Phila Pa 1976). 2001;26(23):2623-8. doi: 10.1097/00007632-200112010-00018. [PubMed: 11725245].
24. Moghaddam A, Zimmermann G, Hammer K, Bruckner T, Grutzner PA, von RJ. Cigarette smoking influences the clinical and occupational outcome of patients with tibial shaft fractures. Injury. 2011;42(12):1435-42. doi: 10.1016/j.injury.2011.05.011. [PubMed: 21665205].
25. Decomas A, Kaye J. Risk factors associated with failure of treatment of humeral diaphyseal fractures after functional bracing. J La State Med Soc. 2010;162(1):33-5. [PubMed: 20336955].
26. Liska F, Haller B, Voss A, Mehl J, Imhoff FB, Willinger L, et al. Smoking and obesity influence the risk of nonunion in lateral opening wedge, closing wedge and torsional distal femoral osteotomies. Knee Surg Sports Traumatol Arthrosc. 2018;26(9):2551-7. doi: 10.1007/s00167-017-4754-9. [PubMed: 29119287].
27. Taitsman LA, Lynch JR, Agel J, Barei DP, Nork SE. Risk factors for femoral nonunion after femoral shaft fracture. J Trauma. 2009;67(6):1389-92. doi: 10.1097/TA.0b013e318182afd0. [PubMed: 19704386].
28. Scolaro JA, Schenker ML, Yannascoli S, Baldwin K, Mehta S, Ahn J. Cigarette smoking increases complications following fracture: a systematic review. J Bone Joint Surg Am. 2014;96(8):674-81. doi: 10.2106/JBJS.M.00081. [PubMed: 24740664].
29. Lindstrom D, Sadr AO, Wladis A, Tonnesen H, Linder S, Nasell H, et al. Effects of a perioperative smoking cessation intervention on postoperative complications: A randomized trial. Ann Surg. 2008;248(5):739-45. doi: 10.1097/SLA.0b013e3181889d0d. [PubMed: 18948800].
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31. Gortler H, Rusyn J, Godbout C, Chahal J, Schemitsch EH, Nauth
A. Diabetes and Healing Outcomes in Lower Extremity Fractures: A Systematic Review. Injury. 2018;49(2):177-83. doi: 10.1016/j.injury.2017.11. [PubMed: 29162268].
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33. Lee M, Choi WJ, Han SH, Jang J, Lee JW. Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail. Foot Ankle Surg. 2018;24(6): 542-8. doi: 10.1016/j.fas.2017.07.006. [PubMed: 29409267].
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36. Goldner WS, Stoner JA, Thompson J, Taylor K, Larson L, Erickson J, et al. Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: A comparison with non-obese controls. Obes Surg. 2008;18(2):145-50. doi: 10.1007/s11695-007-9315-8. [PubMed: 18175194].
37. Tian R, Zheng F, Zhao W, Zhang Y, Yuan J, Zhang B, et al. Prevalence and influencing factors of nonunion in patients with tibial fracture: systematic review and meta-analysis. J Orthop Surg Res. 2020;15(1):377. doi: 10.1186/s13018-020-01904-2. [PubMed: 32883313]. [PubMed Central: PMC7469357].
38. Wijnands KA, Brink PR, Weijers PH, Dejong CH, Poeze M. Impaired fracture healing associated with amino acid disturbances. Am J Clin Nutr. 2012;95(5):1270-7. doi: 10.3945/ajcn.110.009209. [PubMed: 22492379].
39. Meesters DM, Wijnands KAP, Brink PRG, Poeze M. Malnutrition and fracture healing: are specific deficiencies in amino acids important in nonunion development? Nutrients. 2018;10(11):1597. doi: 10.3390/nu10111597. [PubMed: 30384490]. [PubMed Central: PMC6266771].
40. Fischer V, Haffner-Luntzer M, Amling M, Ignatius A. Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover. Eur Cell Mater. 2018;35:365-85. doi: 10.22203/eCM.v035a25. [PubMed: 29931664].
41. Pourfeizi HH, Tabriz A, Elmi A, Aslani H. Prevalence of vitamin D deficiency and secondary hyperparathyroidism in nonunion of traumatic fractures. Acta Med Iran. 2013;51(10):705-10. [PubMed: 24338144].
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2. Bergh C, Wennergren D, Moller M, Brisby H. Fracture incidence in adults in relation to age and gender: A study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area. PLoS One. 2020;15(12):e0244291. doi: 10.1371/journal.pone.0244291. [PubMed: 33347485]. [PubMed Central: PMC7751975].
3. Loi F, Cordova LA, Pajarinen J, Lin TH, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone. 2016;86:119-30. doi: 10.1016/j.bone.2016.02.020. [PubMed: 26946132]. [PubMed Central: PMC4833637].
4. Einhorn TA, Gerstenfeld LC. Fracture healing: Mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45-54. doi: 10.1038/nrrheum.2014.164. [PubMed: 25266456]. [PubMed Central: PMC4464690].
5. Ekegren CL, Edwards ER, de SR, 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(12). doi: 10.3390/ijerph15122845. [PubMed: 30551632]. [PubMed Central: PMC6313538].
6. Wildemann B, Ignatius A, Leung F, Taitsman LA, Smith RM, Pesantez R, et al. Non-union bone fractures. Nat Rev Dis Primers. 2021;7(1):57. doi: 10.1038/s41572-021-00289-8. [PubMed: 34354083].
7. Bell A, Templeman D, Weinlein JC. Nonunion of the femur and tibia: An update. Orthop Clin North Am. 2016;47(2):365-75. doi: 10.1016/j.ocl.2015.09.010. [PubMed: 26772945].
8. 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(11):e162775. doi: 10.1001/jamasurg.2016.2775. [PubMed: 27603155].
9. Tzioupis C, Giannoudis PV. Prevalence of long-bone non- unions. Injury. 2007;38(Suppl 2):S3-S9. doi: 10.1016/s0020- 1383(07)80003-9. [PubMed: 17920415].
10. Mills LA, Aitken SA, Simpson AHRW. The risk of non-union per fracture: Current myths and revised figures from a population of over 4 million adults. Acta Orthop. 2017;88(4):434-9. doi: 10.1080/17453674.2017.1321351. [PubMed: 28508682]. [PubMed Central: PMC5499337].
11. Bhandari M, Fong K, Sprague S, Williams D, Petrisor B. Variability in the definition and perceived causes of delayed unions and nonunions: A cross-sectional, multinational survey of orthopaedic surgeons. J Bone Joint Surg Am. 2012;94(15): e1091-e1096. doi: 10.2106/JBJS.K.01344. [PubMed: 22854998].
12. Whelan DB, Bhandari M, Stephen D, Kreder H, McKee MD, Zdero R, et al. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma. 2010;68(3):629-32. doi: 10.1097/TA.0b013e3181a7c16d. [PubMed: 19996801].
13. Oliver WM, Smith TJ, Nicholson JA, Molyneux SG, White TO, Clement ND, et al. The Radiographic Union Score for HUmeral fractures (RUSHU) predicts humeral shaft nonunion. Bone Joint J. 2019;101-B(10):1300-6. doi: 10.1302/0301-620X.101B10.BJJ- 2019-0304.R1. [PubMed: 31564159].
14. Bhandari M, Chiavaras M, Ayeni O, Chakraverrty R, Parasu N, Choudur H, et al. Assessment of radiographic fracture healing in patients with operatively treated femoral neck fractures. J Orthop Trauma. 2013;27(9):e213-e219. doi: 10.1097/BOT.0b013e318282e692. [PubMed: 23287749].
15. Atwan Y, Schemitsch EH. Radiographic evaluations: Which are most effective to follow fracture healing? Injury. 2020;51(Suppl 2):S18-S22. doi: 10.1016/j.injury.2019.12.028. [PubMed: 31983424].
16. Weber BG, Cech O. Pseudarthrosis: Pathophysiology, biomechanics, therapy, results. New York, NY: Grune & Stratton; 1976. p. 323.
17. Tarakji B, Cil A, Butin RE, Bernhardt M. Adverse effects of smoking on musculoskeletal health. Mo Med. 2017;114(4): 268-71. [PubMed: 30228609]. [PubMed Central: PMC6140077].
18. Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R. Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab. 2009;27(5):555-61. doi: 10.1007/s00774-009-0075-5. [PubMed: 19436947].
19. Mousavi SE, Amini H, Heydarpour P, Amini CF, Godderis L. Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms. Environ Int. 2019;122:67-90. doi: 10.1016/j.envint.2018.11.052. [PubMed: 30509511].
20. Greenhagen RM, Johnson AR, Bevilacqua NJ. Smoking cessation: the role of the foot and ankle surgeon. Foot Ankle Spec. 2010;3(1): 21-8. doi: 10.1177/1938640009352882. [PubMed: 20400436].
21. Cobb TK, Gabrielsen TA, Campbell DC, Wallrichs SL, Ilstrup DM. Cigarette smoking and nonunion after ankle arthrodesis. Foot Ankle Int. 1994;15(2):64-7. doi: 10.1177/107110079401500202. [PubMed: 7981802].
22. Silcox DH 3
, Daftari T, Boden SD, Schimandle JH, Hutton WC, Whitesides TE. The effect of nicotine on spinal fusion. Spine
(Phila Pa 1976). 1995;20(14):1549-53. doi: 10.1097/00007632-
199507150-00001. [PubMed: 7570168].
23. Andersen T, Christensen FB, Laursen M, Hoy K, Hansen ES, Bunger C. Smoking as a predictor of negative outcome in lumbar spinal fusion. Spine (Phila Pa 1976). 2001;26(23):2623-8. doi: 10.1097/00007632-200112010-00018. [PubMed: 11725245].
24. Moghaddam A, Zimmermann G, Hammer K, Bruckner T, Grutzner PA, von RJ. Cigarette smoking influences the clinical and occupational outcome of patients with tibial shaft fractures. Injury. 2011;42(12):1435-42. doi: 10.1016/j.injury.2011.05.011. [PubMed: 21665205].
25. Decomas A, Kaye J. Risk factors associated with failure of treatment of humeral diaphyseal fractures after functional bracing. J La State Med Soc. 2010;162(1):33-5. [PubMed: 20336955].
26. Liska F, Haller B, Voss A, Mehl J, Imhoff FB, Willinger L, et al. Smoking and obesity influence the risk of nonunion in lateral opening wedge, closing wedge and torsional distal femoral osteotomies. Knee Surg Sports Traumatol Arthrosc. 2018;26(9):2551-7. doi: 10.1007/s00167-017-4754-9. [PubMed: 29119287].
27. Taitsman LA, Lynch JR, Agel J, Barei DP, Nork SE. Risk factors for femoral nonunion after femoral shaft fracture. J Trauma. 2009;67(6):1389-92. doi: 10.1097/TA.0b013e318182afd0. [PubMed: 19704386].
28. Scolaro JA, Schenker ML, Yannascoli S, Baldwin K, Mehta S, Ahn J. Cigarette smoking increases complications following fracture: a systematic review. J Bone Joint Surg Am. 2014;96(8):674-81. doi: 10.2106/JBJS.M.00081. [PubMed: 24740664].
29. Lindstrom D, Sadr AO, Wladis A, Tonnesen H, Linder S, Nasell H, et al. Effects of a perioperative smoking cessation intervention on postoperative complications: A randomized trial. Ann Surg. 2008;248(5):739-45. doi: 10.1097/SLA.0b013e3181889d0d. [PubMed: 18948800].
30. Nasell H, Adami J, Samnegard E, Tonnesen H, Ponzer S. Effect of smoking cessation intervention on results of acute fracture surgery: A randomized controlled trial. J Bone Joint Surg Am. 2010;92(6):1335-42. doi: 10.2106/JBJS.I.00627. [PubMed: 20516308].
31. Gortler H, Rusyn J, Godbout C, Chahal J, Schemitsch EH, Nauth
A. Diabetes and Healing Outcomes in Lower Extremity Fractures: A Systematic Review. Injury. 2018;49(2):177-83. doi: 10.1016/j.injury.2017.11. [PubMed: 29162268].
32. Lavery LA, Lavery DC, Green T, Hunt N, La FJ, Kim PJ, et al. Increased risk of nonunion and charcot arthropathy after ankle fracture in people with diabetes. J Foot Ankle Surg. 2020;59(4):653-6. doi: 10.1053/j.jfas.2019.05.006. [PubMed: 32600558].
33. Lee M, Choi WJ, Han SH, Jang J, Lee JW. Uncontrolled diabetes as a potential risk factor in tibiotalocalcaneal fusion using a retrograde intramedullary nail. Foot Ankle Surg. 2018;24(6): 542-8. doi: 10.1016/j.fas.2017.07.006. [PubMed: 29409267].
34. Shibuya N, Humphers JM, Fluhman BL, Jupiter DC. Factors associated with nonunion, delayed union, and malunion in foot and ankle surgery in diabetic patients. J Foot Ankle Surg. 2013;52(2):207-11. doi: 10.1053/j.jfas.2012.11.012. [PubMed: 23313498].
35. Burrus MT, Werner BC, Yarboro SR. Obesity is associated with increased postoperative complications after operative management of tibial shaft fractures. Injury. 2016;47(2):465-70. doi: 10.1016/j.injury.2015.10.026. [PubMed: 26553429].
36. Goldner WS, Stoner JA, Thompson J, Taylor K, Larson L, Erickson J, et al. Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: A comparison with non-obese controls. Obes Surg. 2008;18(2):145-50. doi: 10.1007/s11695-007-9315-8. [PubMed: 18175194].
37. Tian R, Zheng F, Zhao W, Zhang Y, Yuan J, Zhang B, et al. Prevalence and influencing factors of nonunion in patients with tibial fracture: systematic review and meta-analysis. J Orthop Surg Res. 2020;15(1):377. doi: 10.1186/s13018-020-01904-2. [PubMed: 32883313]. [PubMed Central: PMC7469357].
38. Wijnands KA, Brink PR, Weijers PH, Dejong CH, Poeze M. Impaired fracture healing associated with amino acid disturbances. Am J Clin Nutr. 2012;95(5):1270-7. doi: 10.3945/ajcn.110.009209. [PubMed: 22492379].
39. Meesters DM, Wijnands KAP, Brink PRG, Poeze M. Malnutrition and fracture healing: are specific deficiencies in amino acids important in nonunion development? Nutrients. 2018;10(11):1597. doi: 10.3390/nu10111597. [PubMed: 30384490]. [PubMed Central: PMC6266771].
40. Fischer V, Haffner-Luntzer M, Amling M, Ignatius A. Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover. Eur Cell Mater. 2018;35:365-85. doi: 10.22203/eCM.v035a25. [PubMed: 29931664].
41. Pourfeizi HH, Tabriz A, Elmi A, Aslani H. Prevalence of vitamin D deficiency and secondary hyperparathyroidism in nonunion of traumatic fractures. Acta Med Iran. 2013;51(10):705-10. [PubMed: 24338144].
42. Childs BR, Andres BA, Vallier HA. economic benefit of calcium and vitamin d supplementation: Does it outweigh the cost of nonunions? J Orthop Trauma. 2016;30(8):e285-e288. doi: 10.1097/BOT.0000000000000592. [PubMed: 27010185].
43. 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(2):109-12. doi: 10.1016/j.cjtee.2016.01.012. [PubMed: 27140219]. [PubMed Central: PMC4897920].
44. Krappinger D, Wolf B, Dammerer D, Thaler M, Schwendinger P, Lindtner RA. Risk factors for nonunion after intramedullary nailing of subtrochanteric femoral fractures. Arch Orthop Trauma Surg. 2019;139(6):769-77. doi: 10.1007/s00402-019-03131-9. [PubMed: 30729990].
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| Files | ||
| Issue | Vol 8, No 2 (2022) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/jost.v8i2.9309 | |
| Keywords | ||
| Fracture Healing Bone Risk Factors | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Zafari H, Moein SA, Razzaghof M, Mortazavi SJ. The Contributing Factors of Nonunion Bone Fractures: A Brief Review. J Orthop Spine Trauma. 2022;8(2):44-7.
