Fractures Around the Knee—Significant Achievements During the Past 25 Years and Major Questions to Be Solved
Abstract
1. Background
2. Tibial Plateau Fractures
3. Osteosynthesis
4. Arthroscopy/Fracturoscopy
5. Classification
6. New Approaches
7. Complications/Infection Rates
8. Distal Femoral Fractures
9. Patellar Fractures
10. Fibula
11. Bone Graft Substitutes/Biologics
12. Conclusions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Thurig, G.; Korthaus, A.; Frosch, K.H.; Krause, M. The value of magnetic resonance imaging in the preoperative diagnosis of tibial plateau fractures: A systematic literature review. Eur. J. Trauma Emerg. Surg. 2023, 49, 661–679. [Google Scholar] [CrossRef]
- Beisemann, N.; Keil, H.; Swartman, B.; Schnetzke, M.; Franke, J.; Grutzner, P.A.; Vetter, S.Y. Intraoperative 3D imaging leads to substantial revision rate in management of tibial plateau fractures in 559 cases. J. Orthop. Surg. Res. 2019, 14, 236. [Google Scholar] [CrossRef]
- Krause, M.; Preiss, A.; Meenen, N.M.; Madert, J.; Frosch, K.H. “Fracturoscopy” is Superior to Fluoroscopy in the Articular Reconstruction of Complex Tibial Plateau Fractures-An Arthroscopy Assisted Fracture Reduction Technique. J. Orthop. Trauma 2016, 30, 437–444. [Google Scholar] [CrossRef]
- Frosch, K.H.; Korthaus, A.; Thiesen, D.; Frings, J.; Krause, M. The concept of direct approach to lateral tibial plateau fractures and stepwise extension as needed. Eur. J. Trauma Emerg. Surg. 2020, 46, 1211–1219. [Google Scholar] [CrossRef]
- Meulenkamp, B.; Martin, R.; Desy, N.M.; Duffy, P.; Korley, R.; Puloski, S.; Buckley, R. Incidence, Risk Factors, and Location of Articular Malreductions of the Tibial Plateau. J. Orthop. Trauma 2017, 31, 146–150. [Google Scholar] [CrossRef]
- Krause, M.; Muller, G.; Frosch, K.H. Extended medial and extended lateral approach for tibial plateau fractures. Oper. Orthop. Traumatol. 2019, 31, 127–142. [Google Scholar] [CrossRef] [PubMed]
- Zderic, I.; Stoffel, K.; Sommer, C.; Hontzsch, D.; Gueorguiev, B. Biomechanical evaluation of the tension band wiring principle. A comparison between two different techniques for transverse patella fracture fixation. Injury 2017, 48, 1749–1757. [Google Scholar] [CrossRef] [PubMed]
- DeKeyser, G.; Thorne, T.; Martin, B.I.; Haller, J.M. Changing Epidemiology of Distal Femur Fractures: Increase in Geriatric Fractures and Rates of Distal Femur Replacement. J. Am. Acad. Orthop. Surg. 2024, 32, e1289–e1298. [Google Scholar] [CrossRef] [PubMed]
- Bormann, M.; Neidlein, C.; Gassner, C.; Keppler, A.M.; Bogner-Flatz, V.; Ehrnthaller, C.; Prall, W.C.; Bocker, W.; Furmetz, J. Changing patterns in the epidemiology of tibial plateau fractures: A 10-year review at a level-I trauma center. Eur. J. Trauma Emerg. Surg. 2023, 49, 401–409. [Google Scholar] [CrossRef]
- Nieves, J.W.; Bilezikian, J.P.; Lane, J.M.; Einhorn, T.A.; Wang, Y.; Steinbuch, M.; Cosman, F. Fragility fractures of the hip and femur: Incidence and patient characteristics. Osteoporos. Int. 2010, 21, 399–408. [Google Scholar] [CrossRef]
- Rupp, M.; Walter, N.; Pfeifer, C.; Lang, S.; Kerschbaum, M.; Krutsch, W.; Baumann, F.; Alt, V. The Incidence of Fractures Among the Adult Population of Germany-an Analysis from 2009 through 2019. Dtsch. Arztebl. Int. 2021, 118, 665–669. [Google Scholar] [CrossRef]
- Patzold, R.; Spiegl, U.; Wurster, M.; Augat, P.; Gutsfeld, P.; Gonschorek, O.; Buhren, V. Proximal tibial fractures sustained during alpine skiing-incidence and risk factors. Sportverletz. Sportschaden 2013, 27, 207–211. [Google Scholar] [CrossRef] [PubMed]
- Keppler, L.; Keppler, A.M.; Ihle, C.; Minzlaff, P.; Furmetz, J.; Beck, M.; Saier, T. Patients with complex proximal tibial fractures overestimate the prognosis of their injury. Eur. J. Trauma Emerg. Surg. 2022, 48, 1479–1486. [Google Scholar] [CrossRef] [PubMed]
- Raj, M.; Singh, S.K.; Rajput, A.K.; Gill, S.P.; Verma, S.K.; Sonarkar, S.S. The Comparative Analysis of Single Plating Versus Double Plating in the Treatment of Unstable Bicondylar Proximal Tibial Plateau Fractures. Cureus 2023, 15, e46840. [Google Scholar] [CrossRef]
- Menghi, A.; Mazzitelli, G.; Marzetti, E.; Barberio, F.; D’Angelo, E.; Maccauro, G. Complex tibial plateau fractures: A retrospective study and proposal of treatment algorithm. Injury 2017, 48, S1–S6. [Google Scholar] [CrossRef]
- Ozkaya, U.; Parmaksizoglu, A.S. Dual locked plating of unstable bicondylar tibial plateau fractures. Injury 2015, 46, S9–S13. [Google Scholar] [CrossRef]
- van de Pol, G.J.; Iselin, L.D.; Callary, S.A.; Thewlis, D.; Jones, C.F.; Atkins, G.J.; Solomon, L.B. Impaction bone grafting has potential as an adjunct to the surgical stabilisation of osteoporotic tibial plateau fractures: Early results of a case series. Injury 2015, 46, 1089–1096. [Google Scholar] [CrossRef]
- Weimann, A.; Heinkele, T.; Herbort, M.; Schliemann, B.; Petersen, W.; Raschke, M.J. Minimally invasive reconstruction of lateral tibial plateau fractures using the jail technique: A biomechanical study. BMC Musculoskelet. Disord. 2013, 14, 120. [Google Scholar] [CrossRef]
- Jiang, L.; Chen, E.; Huang, L.; Wang, C. Arthroscopy-Assisted Reduction Percutaneous Internal Fixation Versus Open Reduction Internal Fixation for Tibial Plateau Fracture: A Systematic Review and Meta-analysis. Orthop. J. Sports Med. 2021, 9, 23259671211027838. [Google Scholar] [CrossRef] [PubMed]
- Millar, S.C.; Arnold, J.B.; Thewlis, D.; Fraysse, F.; Solomon, L.B. A systematic literature review of tibial plateau fractures: What classifications are used and how reliable and useful are they? Injury 2018, 49, 473–490. [Google Scholar] [CrossRef]
- Doornberg, J.N.; Rademakers, M.V.; van den Bekerom, M.P.; Kerkhoffs, G.M.; Ahn, J.; Steller, E.P.; Kloen, P. Two-dimensional and three-dimensional computed tomography for the classification and characterisation of tibial plateau fractures. Injury 2011, 42, 1416–1425. [Google Scholar] [CrossRef]
- Kfuri, M.; Schatzker, J. Revisiting the Schatzker classification of tibial plateau fractures. Injury 2018, 49, 2252–2263. [Google Scholar] [CrossRef] [PubMed]
- Krause, M.; Preiss, A.; Muller, G.; Madert, J.; Fehske, K.; Neumann, M.V.; Domnick, C.; Raschke, M.; Sudkamp, N.; Frosch, K.H. Intra-articular tibial plateau fracture characteristics according to the “Ten segment classification”. Injury 2016, 47, 2551–2557. [Google Scholar] [CrossRef]
- Meinberg, E.G.; Agel, J.; Roberts, C.S.; Karam, M.D.; Kellam, J.F. Fracture and Dislocation Classification Compendium-2018. J. Orthop. Trauma 2018, 32, S1–S170. [Google Scholar] [CrossRef]
- Gonzalez, L.J.; Lott, A.; Konda, S.; Egol, K.A. The Hyperextension Tibial Plateau Fracture Pattern: A Predictor of Poor Outcome. J. Orthop. Trauma 2017, 31, e369–e374. [Google Scholar] [CrossRef] [PubMed]
- Bu, G.; Sun, W.; Lu, Y.; Cui, M.; Zhang, X.; Lu, J.; Zhang, J.; Sun, J. Complications associated with hyperextension bicondylar tibial plateau fractures: A retrospective study. BMC Surg. 2021, 21, 299. [Google Scholar] [CrossRef] [PubMed]
- Kokkalis, Z.T.; Iliopoulos, I.D.; Pantazis, C.; Panagiotopoulos, E. What’s new in the management of complex tibial plateau fractures? Injury 2016, 47, 1162–1169. [Google Scholar] [CrossRef]
- Young, M.J.; Barrack, R.L. Complications of internal fixation of tibial plateau fractures. Orthop. Rev. 1994, 23, 149–154. [Google Scholar]
- Solomon, L.B.; Stevenson, A.W.; Lee, Y.C.; Baird, R.P.; Howie, D.W. Posterolateral and anterolateral approaches to unicondylar posterolateral tibial plateau fractures: A comparative study. Injury 2013, 44, 1561–1568. [Google Scholar] [CrossRef]
- Demey, G.; Damayanthi, E.D.; Surg, R.; Dejour, D. The Intact Meniscal “Bucket-Handle” Technique to Expose Complex Lateral Tibial Plateau Fractures. Arthrosc. Tech. 2025, 14, 103165. [Google Scholar] [CrossRef]
- Krause, M.; Frings, J.; Frosch, K.H. The lateral femoral epicondyle osteotomy-an extended surgical approach for comminuted tibial plateau fractures. Injury 2020, 51, 2993–2994. [Google Scholar] [CrossRef]
- Guttowski, D.; Krause, M.; Puschel, K.; Kolb, J.P.; Hartel, M.; Frosch, K.H. Improved Visualization by Central Subluxation of the Lateral Meniscus in Comminuted Lateral Tibial Plateau Fractures. J. Knee Surg. 2021, 34, 1408–1412. [Google Scholar] [CrossRef]
- Krause, M.; Frings, J.; Isik, H.; Frosch, K.H. Comparison of extended lateral approaches to the tibial plateau: The articular exposure of lateral epicondyle osteotomy with and without popliteus tendon vs. fibula osteotomy. Injury 2020, 51, 1874–1878. [Google Scholar] [CrossRef] [PubMed]
- Krause, M.; Frosch, K.H. Change in the treatment of tibial plateau fractures. Unfallchirurgie 2022, 125, 527–534. [Google Scholar] [CrossRef] [PubMed]
- Eggli, S.; Hartel, M.J.; Kohl, S.; Haupt, U.; Exadaktylos, A.K.; Roder, C. Unstable bicondylar tibial plateau fractures: A clinical investigation. J. Orthop. Trauma 2008, 22, 673–679. [Google Scholar] [CrossRef] [PubMed]
- Herbst, E.; Wessolowski, M.A.; Raschke, M.J. Extension of the Medial Approach to the Tibial Plateau via an Osteotomy of the Tibial Insertion of the Superficial Medial Collateral Ligament. J. Clin. Med. 2023, 12, 5208. [Google Scholar] [CrossRef]
- Lobenhoffer, P.; Gerich, T.; Bertram, T.; Lattermann, C.; Pohlemann, T.; Tscheme, H. Particular posteromedial and posterolateral approaches for the treatment of tibial head fractures. Unfallchirurg 1997, 100, 957–967. [Google Scholar] [CrossRef]
- Schwartz, L.; Ganta, A.; Konda, S.; Rivero, S.; Egol, K. The prone posteromedial approach to the knee revisited: A safe and effective strategy for posterior tibial plateau fractures. Eur. J. Orthop. Surg. Traumatol. 2024, 34, 1147–1151. [Google Scholar] [CrossRef]
- Egol, K.A.; Su, E.; Tejwani, N.C.; Sims, S.H.; Kummer, F.J.; Koval, K.J. Treatment of complex tibial plateau fractures using the less invasive stabilization system plate: Clinical experience and a laboratory comparison with double plating. J. Trauma 2004, 57, 340–346. [Google Scholar] [CrossRef]
- Henkelmann, R.; Glaab, R.; Mende, M.; Ull, C.; Braun, P.J.; Katthagen, C.; Gensior, T.J.; Frosch, K.H.; Hepp, P.; Committee TRAUMA of the AGA-Society for Arthroscopy and Joint Surgery; et al. Impact of surgical site infection on patients’ outcome after fixation of tibial plateau fractures: A retrospective multicenter study. BMC Musculoskelet. Disord. 2021, 22, 531. [Google Scholar] [CrossRef]
- Major Extremity Trauma Research Consortium (METRC); O’Toole, R.V.; Joshi, M.; Carlini, A.R.; Murray, C.K.; Allen, L.E.; Huang, Y.; Scharfstein, D.O.; O’Hara, N.N.; Gary, J.L.; et al. Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial. JAMA Surg. 2021, 156, e207259. [Google Scholar] [CrossRef]
- Roy, D.; Ramski, D.; Malige, A.; Beck, M.; Jeffers, K.; Brogle, P. Injury patterns and outcomes associated with fractures of the native distal femur in adults. Eur. J. Trauma Emerg. Surg. 2021, 47, 1123–1128. [Google Scholar] [CrossRef]
- Paley, D.; Pfeil, J. Principles of deformity correction around the knee. Orthopade 2000, 29, 18–38. [Google Scholar] [CrossRef] [PubMed]
- Ebraheim, N.A.; Kelley, L.H.; Liu, X.; Thomas, I.S.; Steiner, R.B.; Liu, J. Periprosthetic Distal Femur Fracture after Total Knee Arthroplasty: A Systematic Review. Orthop. Surg. 2015, 7, 297–305. [Google Scholar] [CrossRef] [PubMed]
- Ehlinger, M.; Ducrot, G.; Adam, P.; Bonnomet, F. Distal femur fractures. Surgical techniques and a review of the literature. Orthop. Traumatol. Surg. Res. 2013, 99, 353–360. [Google Scholar] [CrossRef] [PubMed]
- Lodde, M.F.; Raschke, M.J.; Stolberg-Stolberg, J.; Everding, J.; Rosslenbroich, S.; Katthagen, J.C. Union rates and functional outcome of double plating of the femur: Systematic review of the literature. Arch. Orthop. Trauma Surg. 2022, 142, 1009–1030. [Google Scholar] [CrossRef]
- Sain, A.; Sharma, V.; Farooque, K.; V, M.; Pattabiraman, K. Dual Plating of the Distal Femur: Indications and Surgical Techniques. Cureus 2019, 11, e6483. [Google Scholar] [CrossRef]
- Onay, T.; Gulabi, D.; Colak, I.; Bulut, G.; Gumustas, S.A.; Cecen, G.S. Surgically treated Hoffa Fractures with poor long-term functional results. Injury 2018, 49, 398–403. [Google Scholar] [CrossRef]
- Nork, S.E.; Segina, D.N.; Aflatoon, K.; Barei, D.P.; Henley, M.B.; Holt, S.; Benirschke, S.K. The association between supracondylar-intercondylar distal femoral fractures and coronal plane fractures. J. Bone Jt. Surg. Am. 2005, 87, 564–569. [Google Scholar] [CrossRef]
- Letenneur, J.; Labour, P.E.; Rogez, J.M.; Lignon, J.; Bainvel, J.V. Hoffa’s fractures. Report of 20 cases (author’s transl). Ann. Chir. 1978, 32, 213–219. [Google Scholar]
- Shawky, M.; Abdel Karim, M.; Samir Mohamed Farahat, A.; Goda El-Hamalawy, A. Management of distal femoral fractures: A review article. J. Clin. Orthop. Trauma 2023, 46, 102291. [Google Scholar] [CrossRef]
- Orapiriyakul, W.; Apivatthakakul, T.; Buranaphatthana, T. How to determine the surgical approach in Hoffa fractures? Injury 2018, 49, 2302–2311. [Google Scholar] [CrossRef]
- Wagih, A.M. Arthroscopic Management of a Posterior Femoral Condyle (Hoffa) Fracture: Surgical Technique. Arthrosc. Tech. 2015, 4, e299–e303. [Google Scholar] [CrossRef]
- Lotke, P.A.; Ecker, M.L. Transverse fractures of the patella. Clin. Orthop. Relat. Res. 1981, 158, 180–184. [Google Scholar] [CrossRef]
- Torchia, M.E.; Lewallen, D.G. Open fractures of the patella. J. Orthop. Trauma 1996, 10, 403–409. [Google Scholar] [CrossRef]
- Kruse, M.; Wolf, O.; Mukka, S.; Brüggemann, A. Epidemiology, classification and treatment of patella fractures: An observational study of 3194 fractures from the Swedish Fracture Register. Eur. J. Trauma Emerg. Surg. 2022, 48, 4727–4734. [Google Scholar] [CrossRef]
- Byun, S.E.; Sim, J.A.; Joo, Y.B.; Kim, J.W.; Choi, W.; Na, Y.G.; Shon, O.J. Changes in patellar fracture characteristics: A multicenter retrospective analysis of 1596 patellar fracture cases between 2003 and 2017. Injury 2019, 50, 2287–2291. [Google Scholar] [CrossRef]
- Konan, S.; Sandiford, N.; Unno, F.; Masri, B.S.; Garbuz, D.S.; Duncan, C.P. Periprosthetic fractures associated with total knee arthroplasty: An update. Bone Jt. J. 2016, 98-B, 1489–1496. [Google Scholar] [CrossRef]
- Baid, M.; Narula, S.; Manara, J.R.; Blakeney, W. Evolution in the Management of Patella Fractures. J. Clin. Med. 2024, 13, 1426. [Google Scholar] [CrossRef]
- Rau, Y.; Huynh, T.; Frosch, K.H.; Schultz, C.; Schulz, A.P. Developments in the epidemiology and surgical management of patella fractures in Germany. BMC Musculoskelet. Disord. 2023, 24, 83. [Google Scholar] [CrossRef]
- Wagner, F.C.; Neumann, M.V.; Wolf, S.; Jonaszik, A.; Izadpanah, K.; Piatek, S.; Sudkamp, N.P. Biomechanical comparison of a 3.5 mm anterior locking plate to cannulated screws with anterior tension band wiring in comminuted patellar fractures. Injury 2020, 51, 1281–1287. [Google Scholar] [CrossRef]
- Wild, M.; Eichler, C.; Thelen, S.; Jungbluth, P.; Windolf, J.; Hakimi, M. Fixed-angle plate osteosynthesis of the patella-an alternative to tension wiring? Clin. Biomech. 2010, 25, 341–347. [Google Scholar] [CrossRef]
- Wurm, S.; Augat, P.; Buhren, V. Biomechanical Assessment of Locked Plating for the Fixation of Patella Fractures. J. Orthop. Trauma 2015, 29, e305–e308. [Google Scholar] [CrossRef]
- Lazaro, L.E.; Wellman, D.S.; Pardee, N.C.; Gardner, M.J.; Toro, J.B.; Macintyre, N.R., 3rd; Helfet, D.L.; Lorich, D.G. Effect of computerized tomography on classification and treatment plan for patellar fractures. J. Orthop. Trauma 2013, 27, 336–344. [Google Scholar] [CrossRef]
- Fehske, K.; Berninger, M.T.; Alm, L.; Hoffmann, R.; Zellner, J.; Kosters, C.; Barzen, S.; Raschke, M.J.; Izadpanah, K.; Herbst, E.; et al. Current treatment standard for patella fractures in Germany. Unfallchirurg 2021, 124, 832–838. [Google Scholar] [CrossRef]
- Wang, X.; Yang, H.; Xu, C.; Xu, X.; Zhang, C.; Jing, J. Effect of Schatzker type VI tibial plateau fractures combined with a proximal fibular and/or posterolateral joint facet fracture on early postoperative functional recovery. J. Orthop. Surg. Res. 2023, 18, 412. [Google Scholar] [CrossRef]
- Carrera, I.; Gelber, P.E.; Chary, G.; Gomez Masdeu, M.; Gonzalez Ballester, M.A.; Monllau, J.C.; Noailly, J. An intact fibula may contribute to allow early weight bearing in surgically treated tibial plateau fractures. Knee Surg. Sports Traumatol. Arthrosc. 2018, 26, 756–761. [Google Scholar] [CrossRef]
- Veitch, S.W.; Stroud, R.M.; Toms, A.D. Compaction bone grafting in tibial plateau fracture fixation. J. Trauma 2010, 68, 980–983. [Google Scholar] [CrossRef]
- Simpson, D.; Keating, J.F. Outcome of tibial plateau fractures managed with calcium phosphate cement. Injury 2004, 35, 913–918. [Google Scholar] [CrossRef]
- Lobenhoffer, P.; Gerich, T.; Witte, F.; Tscherne, H. Use of an injectable calcium phosphate bone cement in the treatment of tibial plateau fractures: A prospective study of twenty-six cases with twenty-month mean follow-up. J. Orthop. Trauma 2002, 16, 143–149. [Google Scholar] [CrossRef]
- Welch, R.D.; Zhang, H.; Bronson, D.G. Experimental tibial plateau fractures augmented with calcium phosphate cement or autologous bone graft. J. Bone Jt. Surg. Am. 2003, 85, 222–231. [Google Scholar] [CrossRef]
- Segur, J.M.; Torner, P.; Garcia, S.; Combalia, A.; Suso, S.; Ramon, R. Use of bone allograft in tibial plateau fractures. Arch. Orthop. Trauma Surg. 1998, 117, 357–359. [Google Scholar] [CrossRef]
- Goff, T.; Kanakaris, N.K.; Giannoudis, P.V. Use of bone graft substitutes in the management of tibial plateau fractures. Injury 2013, 44, S86–S94. [Google Scholar] [CrossRef]
- Prall, W.C.; Kusmenkov, T.; Schmidt, B.; Furmetz, J.; Haasters, F.; Naendrup, J.H.; Bocker, W.; Shafizadeh, S.; Mayr, H.O.; Pfeiffer, T.R. Cancellous allogenic and autologous bone grafting ensure comparable tunnel filling results in two-staged revision ACL surgery. Arch. Orthop. Trauma Surg. 2020, 140, 1211–1219. [Google Scholar] [CrossRef]
- Garabano, G.; Perez Alamino, L.; Rodriguez, J.; Alonso, M.; Angel Pesciallo, C. Maintenance of joint reduction and allograft incorporation in treating tibial plateau fractures. Retrospective case series using cortico-cancellous, non-irradiated, bone allograft. J. Clin. Orthop. Trauma 2024, 54, 102491. [Google Scholar] [CrossRef] [PubMed]
- Impieri, L.; Pezzi, A.; Hadad, H.; Peretti, G.M.; Mangiavini, L.; Rossi, N. Orthobiologics in delayed union and non-union of adult long bones fractures: A systematic review. Bone Rep. 2024, 21, 101760. [Google Scholar] [CrossRef] [PubMed]





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Stockinger, M.; Krause, M.; Frosch, K.-H. Fractures Around the Knee—Significant Achievements During the Past 25 Years and Major Questions to Be Solved. J. Clin. Med. 2026, 15, 3463. https://doi.org/10.3390/jcm15093463
Stockinger M, Krause M, Frosch K-H. Fractures Around the Knee—Significant Achievements During the Past 25 Years and Major Questions to Be Solved. Journal of Clinical Medicine. 2026; 15(9):3463. https://doi.org/10.3390/jcm15093463
Chicago/Turabian StyleStockinger, Matthias, Matthias Krause, and Karl-Heinz Frosch. 2026. "Fractures Around the Knee—Significant Achievements During the Past 25 Years and Major Questions to Be Solved" Journal of Clinical Medicine 15, no. 9: 3463. https://doi.org/10.3390/jcm15093463
APA StyleStockinger, M., Krause, M., & Frosch, K.-H. (2026). Fractures Around the Knee—Significant Achievements During the Past 25 Years and Major Questions to Be Solved. Journal of Clinical Medicine, 15(9), 3463. https://doi.org/10.3390/jcm15093463

