Demographics of the Study Cohort
The average age of the study cohort was approximately 57 years (Table V). When nonunion was diagnosed by blinded CT assessment (in 18% of the patients), BMI, smoking status, and work status differed significantly between the union and nonunion groups. The BMI was 2 kg/m2 higher in the nonunion group (mean and standard deviation, 32.6 ± 5.7 kg/m2) compared with the union group (30.4 ± 5.7 kg/m2); 67% of the nonunion group but only 45% of the union group had a BMI of >30 kg/m2 (p = 0.0011). Union was achieved in 68% of current smokers compared with 84% of non-smokers (p = 0.0198), 90% of employed patients compared with 75% of patients who were not working (p < 0.0001), 74% of patients with diabetes compared with 83% of patients without diabetes (difference not significant), and 84% of patients who underwent fusion of 1 joint, 79% of those who underwent fusion of 2 joints, and 78% of those who underwent fusion of 3 joints (difference not significant). For a patient to be included in the union group, all joints treated in that patient had to demonstrate union; hence, lower fusion rates in patients who underwent fusion of multiple joints were expected. In summary, nonunion was more likely in obese patients who smoked and were not working.
When nonunion was determined by surgeon assessment (5% nonunion rate), there were no significant differences in baseline characteristics between the union and nonunion groups.
When patient demographics were stratified according to the assessment method and union status (Table VI), BMI and work status differed significantly: i.e., nonunion was more likely in obese patients who were not working.
One year after ankle and/or hindfoot arthrodesis, 18% of the patients demonstrated nonunion on blinded CT assessment and 5.4% presented with nonunion based on surgeon evaluation that included clinical, radiographic, and CT parameters. Irrespective of the assessment method, patients with a nonunion had worse AOFAS-AHS and FFI (functional) scores than patients with successful fusion and lower SF-12 PCS scores, indicating an impact on quality of life. The differences between the union and nonunion groups for all 3 outcome measures were clinically meaningful24-26 regardless of the method used to assess nonunion. These findings illustrate the importance of achieving union following foot and ankle fusion procedures to attain a good outcome and a better quality of life. Patients with a nonunion according to blinded CT assessment were more likely to be overweight, smokers, and not working.
Review of these data suggests that future studies should use blinded CT assessment to define nonunion rather than rely on surgeon assessment. Surgeon assessment of nonunion is methodologically flawed as clinical outcome is a component. Furthermore, the concept of an asymptomatic nonunion is not supported by this study, as nonunion identified by CT imaging resulted in a worse outcome.
The functional outcomes were substantially better in the union group than in the nonunion group and are consistent with the literature. Studies of ankle arthrodesis demonstrated mean AOFAS scores of 67 points in 66 ankles after 9 years of follow-up28, 75.6 points in 21 patients after 35 months29, and 68.3 points in 16 patients with ≥6 months of follow-up30. A mean FFI of 17.6 points was reported for 34 patients at a median of 3.6 years after ankle arthrodesis31.
While nonunion is defined as incomplete osseous healing at ≥6 months following arthrodesis14, there is no consensus on the amount of osseous healing that constitutes “complete” versus “incomplete” healing or on how nonunions are assessed. A review of 12 studies published since 2000 that included a total of 961 ankle arthrodeses7,12,16-18,32-38 indicated that an average of 11% (range, 3% to 23%) of the procedures resulted in nonunion. Some authors defined nonunion on the basis of radiographic findings only16,18,35-37, whereas others relied on a combination of clinical and radiographic assessment7,12,17,32-34,38. Recently, CT has been proposed to provide a more sensitive, reliable, and accurate assessment of fusion13,15,39. Coughlin et al.13 suggested that 50% osseous bridging of the posterior facet of the subtalar joint on CT closely correlates with successful clinical outcomes. Dorsey et al.39 reported that clinically stable joints demonstrated fusion of ≥33.2% on CT, equivalent to the 50% osseous bridging recommended by Coughlin et al.13 if the same methodology is applied. Glazebrook et al.15 found a clinically important improvement in SF-12, FFI, and AOFAS-AHS scores in patients with at least 25% to 49% osseous bridging at fusion sites on CT, which is consistent with our results for patients assessed by blinded CT.
Despite the inclusion of patients with risk factors for nonunion (i.e., overweight, diabetes, smoking, substantial deformity, and intra-articular erosions) in the current study, the overall prevalence of nonunion was 5.4% at 1 year as diagnosed with surgeon assessment, compared with 11% for ankle and hindfoot arthrodeses reported in the literature7,12,16-18,32-38. The patients in our study were all treated with autologous bone graft or bone substitute to maximize fusion.
Nonunion following arthrodesis is likely determined by a combination of risk factors7,32. Nonunion following elective foot and ankle surgery is reportedly more frequent in smokers, in the presence of avascular bone at the arthrodesis site, and in patients in whom previous arthrodeses have failed7,40,41. Nonunion also appears to be more frequent in diabetic and obese patients4,42. In the current study, nonunion diagnosed with blinded CT assessment was found more often in patients who were overweight, smoked, or were not working.
A strength of this study is the use of prospectively collected clinical, radiographic, and CT data from a randomized, controlled, blinded, multicenter rhPDGF-BB trial, which ensured that all patients enrolled in the trial, rather than only those presenting with clinical symptoms, were evaluated for the presence of nonunion. Another strength is the large sample size of 389 ankle and hindfoot arthrodeses, the largest longitudinal study cohort to our knowledge.
This study also had limitations, including the relatively short follow-up period of 12 months. It is not clear whether the clinical results after nonunion may improve on longer follow-up or whether some cases of nonunion may deteriorate with time and cause more symptoms. The various arthrodesis sites in the patients in this study may have added confounding variables to the statistical analyses. In the analyses based on the surgeon’s composite evaluation of union, the small numbers in the nonunion group and subsequent low power may have precluded the determination of significant differences in baseline characteristics. Additionally, this assessment method introduces bias, as clinical outcome was one component of the evaluation.
In conclusion, this study demonstrated poorer 1-year functional results in patients with nonunion compared with patients who obtained fusion following ankle and hindfoot arthrodesis. Achieving solid osseous union is required for good functional outcomes.
NOTE: The following North American Orthopedic Foot and Ankle Study Group investigators participated in the original randomized controlled trial: Nicholas A. Abidi, MD; Jorge I. Acevedo, MD; John Anderson, MD; Robert Anderson, MD; Wayne Berberian, MD; Gregory C. Berlet, MD; Christopher Bibbo, DO; Donald Bohay, MD; Bradley J. Brainard, DO, MD; Bruce Cohen, MD; W. Hodges Davis, MD; Keith Donatto, MD; Hugh Dougall, MD, FRCSC; Mark E. Easley, MD; Andrew A. Elliott, MD; Adolph Samuel Flemister Jr., MD; William Granberry, MD; Justin Greisberg, MD; Steven L. Haddad, MD; Anthony Hinz, MD; Susan N. Ishikawa, MD; Juha I. Jaakkola, MD; Johnny Lau, MSc, MD, FRCSC; Ian Le, MD, FRCSC; Thomas Lee, MD; Sheldon S. Lin, MD; John Maskill, MD; G. Andrew Murphy, MD; Steven K. Neufeld, MD; M.J. O’Malley, MD; Murray Penner, MD, FRCSC; Terrence Philbin, DO; Steven Raikin, MD; Iain Russell, MD, FRCSC; Lew Schon, MD; James J. Sferra, MD; Naomi Shields, MD; Nebojsa Skrepnik, MD, PhD; Raymond Sullivan, MD; Michael Swords, DO; A. Brian Thomson, MD; Troy Watson, MD; and Kevin Wing, MD, FRCSC. The authors thank Dagmar Gross for assistance with preparation of the manuscript.
Investigation performed at the University of British Columbia in collaboration with the North American Orthopedic Foot and Ankle Study Group
Disclosure: One author was an employee of BioMimetic Therapeutics, Inc. (Wright Medical, Inc.) at the time that this study was conducted. The remaining authors received funding to cover research costs through an unrestricted grant and/or were working as consultants for BioMimetic Therapeutics, Inc. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work.
1. Abidi NA, Gruen GS, Conti SF. Ankle arthrodesis: indications and techniques. J Am Acad Orthop Surg. 2000 ;8(3):200–9.
2. Charnley J. Compression arthrodesis of the ankle and shoulder. J Bone Joint Surg Br. 1951 ;33B(2):180–91.
3. Mann RA, Rongstad KM. Arthrodesis of the ankle: a critical analysis. Foot Ankle Int. 1998 ;19(1):3–9.
4. Perlman MH, Thordarson DB. Ankle fusion in a high risk population: an assessment of nonunion risk factors. Foot Ankle Int. 1999 ;20(8):491–6.
5. Valderrabano V, Horisberger M, Russell I, Dougall H, Hintermann B. Etiology of ankle osteoarthritis. Clin Orthop Relat Res. 2009 ;467(7):1800–6. Epub 2008 Oct 2.
6. Glazebrook M, Daniels T, Younger A, Foote CJ, Penner M, Wing K, Lau J, Leighton R, Dunbar M. Comparison of health-related quality of life between patients with end-stage ankle and hip arthrosis. J Bone Joint Surg Am. 2008 ;90(3):499–505.
7. Easley ME, Trnka HJ, Schon LC, Myerson MS. Isolated subtalar arthrodesis. J Bone Joint Surg Am. 2000 ;82(5):613–24.
8. Russotti GM, Cass JR, Johnson KA. Isolated talocalcaneal arthrodesis. A technique using moldable bone graft. J Bone Joint Surg Am. 1988 ;70(10):1472–8.
9. Cheng YM, Chen SK, Chen JC, Wu WL, Huang PJ, Chiang HC, Lin CY. Revision of ankle arthrodesis. Foot Ankle Int. 2003 ;24(4):321–5.
10. Kitaoka HB, Anderson PJ, Morrey BF. Revision of ankle arthrodesis with external fixation for non-union. J Bone Joint Surg Am. 1992 ;74(8):1191–200.
11. Kitaoka HB, Alexander IJ, Adelaar RS, Nunley JA, Myerson MS, Sanders M. Clinical rating systems for the ankle-hindfoot, midfoot, hallux, and lesser toes. Foot Ankle Int. 1994 ;15(7):349–53.
12. Thordarson DB, Kuehn S. Use of demineralized bone matrix in ankle/hindfoot fusion. Foot Ankle Int. 2003 ;24(7):557–60.
13. Coughlin MJ, Grimes JS, Traughber PD, Jones CP. Comparison of radiographs and CT scans in the prospective evaluation of the fusion of hindfoot arthrodesis. Foot Ankle Int. 2006 ;27(10):780–7.
14. Weber BG, Czech O. Pseudarthrosen. Bern: Huber; 1973.
15. Glazebrook M, Beasley W, Daniels T, Evangelista PT, Donahue R, Younger A, Pinzur MS, Baumhauer JF, DiGiovanni CW. Establishing the relationship between clinical outcome and extent of osseous bridging between computed tomography assessment in isolated hindfoot and ankle fusions. Foot Ankle Int. 2013 ;34(12):1612–8. Epub 2013 Sep 16.
16. Gougoulias NE, Agathangelidis FG, Parsons SW. Arthroscopic ankle arthrodesis. Foot Ankle Int. 2007 ;28(6):695–706.
17. Strasser NL, Turner NS. Functional outcomes after ankle arthrodesis in elderly patients. Foot Ankle Int. 2012 ;33(9):699–703.
18. Chalayon O, Wang B, Blankenhorn B, Jackson JB 3rd, Beals T, Nickisch F, Saltzman CL. Factors affecting the outcomes of uncomplicated primary open ankle arthrodesis. Foot Ankle Int. 2015 ;36(10):1170–9. Epub 2015 May 20.
19. Frey C, Halikus NM, Vu-Rose T, Ebramzadeh E. A review of ankle arthrodesis: predisposing factors to nonunion. Foot Ankle Int. 1994 ;15(11):581–4.
20. Thevendran G, Younger A, Pinney S. Current concepts review: risk factors for nonunions in foot and ankle arthrodeses. Foot Ankle Int. 2012 ;33(11):1031–40.
21. DiGiovanni CW, Lin SS, Baumhauer JF, Daniels T, Younger A, Glazebrook M, Anderson J, Anderson R, Evangelista P, Lynch SE; North American Orthopedic Foot and Ankle Study Group. Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP): an alternative to autogenous bone graft. J Bone Joint Surg Am. 2013 ;95(13):1184–92.
22. Budiman-Mak E, Conrad KJ, Roach KE. The Foot Function Index: a measure of foot pain and disability. J Clin Epidemiol. 1991;44(6):561–70.
23. Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 ;34(3):220–33.
24. Dawson J, Doll H, Coffey J, Jenkinson C; Oxford and Birmingham Foot and Ankle Clinical Research Group. Responsiveness and minimally important change for the Manchester-Oxford Foot Questionnaire (MOXFQ) compared with AOFAS and SF-36 assessments following surgery for hallux valgus. Osteoarthritis Cartilage. 2007 ;15(8):918–31. Epub 2007 Mar 26.
25. Landorf KB, Radford JA. Minimal important difference: values for the Foot Health Status Questionnaire, Foot Function Index and visual analogue scale. Foot. 2008;18(1):15–9.
26. Clement ND, MacDonald D, Simpson AH. The minimal clinically important difference in the Oxford knee score and Short Form 12 score after total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2014 ;22(8):1933–9. Epub 2013 Nov 20.
27. Madeley NJ, Wing KJ, Topliss C, Penner MJ, Glazebrook MA, Younger AS. Responsiveness and validity of the SF-36, Ankle Osteoarthritis Scale, AOFAS Ankle Hindfoot Score, and Foot Function Index in end stage ankle arthritis. Foot Ankle Int. 2012 ;33(1):57–63.
28. Hendrickx RP, Stufkens SA, de Bruijn EE, Sierevelt IN, van Dijk CN, Kerkhoffs GM. Medium- to long-term outcome of ankle arthrodesis. Foot Ankle Int. 2011 ;32(10):940–7.
29. Schuh R, Hofstaetter J, Krismer M, Bevoni R, Windhager R, Trnka HJ. Total ankle arthroplasty versus ankle arthrodesis. Comparison of sports, recreational activities and functional outcome. Int Orthop. 2012 ;36(6):1207–14. Epub 2011 Dec 16.
30. Braito M, Dammerer D, Kaufmann G, Fischler S, Carollo J, Reinthaler A, Huber D, Biedermann R. Are our expectations bigger than the results we achieve? A comparative study analysing potential advantages of ankle arthroplasty over arthrodesis. Int Orthop. 2014 ;38(8):1647–53. Epub 2014 Jul 2.
31. Stegeman M, van Ginneken BT, Boetes B, Tuinhout M, Louwerens JW, Swierstra BA. Can diagnostic injections predict the outcome in foot and ankle arthrodesis? BMC Musculoskelet Disord. 2014;15(11):11. Epub 2014 Jan 9.
32. Ferkel RD, Hewitt M. Long-term results of arthroscopic ankle arthrodesis. Foot Ankle Int. 2005 ;26(4):275–80.
33. Pelton K, Hofer JK, Thordarson DB. Tibiotalocalcaneal arthrodesis using a dynamically locked retrograde intramedullary nail. Foot Ankle Int. 2006 ;27(10):759–63.
34. Colman AB, Pomeroy GC. Transfibular ankle arthrodesis with rigid internal fixation: an assessment of outcome. Foot Ankle Int. 2007 ;28(3):303–7.
35. Niinimäki TT, Klemola TM, Leppilahti JI. Tibiotalocalcaneal arthrodesis with a compressive retrograde intramedullary nail: a report of 34 consecutive patients. Foot Ankle Int. 2007 ;28(4):431–4.
36. Bibbo C, Patel DV, Haskell MD. Recombinant bone morphogenetic protein-2 (rhBMP-2) in high-risk ankle and hindfoot fusions. Foot Ankle Int. 2009 ;30(7):597–603.
37. Herrera-Pérez M, Andarcia-Bañuelos C, Barg A, Wiewiorski M, Valderrabano V, Kapron AL, De Bergua-Domingo JM, Pais-Brito JL. Comparison of cannulated screws versus compression staples for subtalar arthrodesis fixation. Foot Ankle Int. 2015 ;36(2):203–10. Epub 2014 Sep 23.
38. Röhm J, Zwicky L, Horn Lang T, Salentiny Y, Hintermann B, Knupp M. Mid- to long-term outcome of 96 corrective hindfoot fusions in 84 patients with rigid flatfoot deformity. Bone Joint J. 2015 ;97-B(5):668–74.
39. Dorsey ML, Liu PT, Roberts CC, Kile TA. Correlation of arthrodesis stability with degree of joint fusion on MDCT. AJR Am J Roentgenol. 2009 ;192(2):496–9.
40. Ishikawa SN, Murphy GA, Richardson EG. The effect of cigarette smoking on hindfoot fusions. Foot Ankle Int. 2002 ;23(11):996–8.
41. Cobb TK, Gabrielsen TA, Campbell DC 2nd, Wallrichs SL, Ilstrup DM. Cigarette smoking and nonunion after ankle arthrodesis. Foot Ankle Int. 1994 ;15(2):64–7.
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42. Collman DR, Kaas MH, Schuberth JM. Arthroscopic ankle arthrodesis: factors influencing union in 39 consecutive patients. Foot Ankle Int. 2006 ;27(12):1079–85.