1. Anterior Cruciate Ligament Reconstruction: Autograft versus Allograft By: Sarah Taylor Evidence Based Medicine February 2009

2. PICO Question Patient: Athletic patients ages 15-30 with complete anterior cruciate ligament (ACL) tear Patient: Athletic patients ages 15-30 with complete anterior cruciate ligament (ACL) tear Intervention: Autograft reconstruction Intervention: Autograft reconstruction Comparison: Allograft reconstruction Comparison: Allograft reconstruction Outcome: Fully restored knee function (range of motion, stability, etc.) as well as decreased morbidity (quadriceps weakness, patellofemoral pain, loss of motion, early degenerative changes, arthrofibrosis, infection, etc.) and likelihood of revision. Outcome: Fully restored knee function (range of motion, stability, etc.) as well as decreased morbidity (quadriceps weakness, patellofemoral pain, loss of motion, early degenerative changes, arthrofibrosis, infection, etc.) and likelihood of revision.

3. Epidemiology Approximately 1 in 3000 people in the United States suffer ACL injuries each year Approximately 1 in 3000 people in the United States suffer ACL injuries each year Women 4x greater risk than men Women 4x greater risk than men 70% Sports-related 70% Sports-related More than 100,000 ACL reconstructions being performed annually More than 100,000 ACL reconstructions being performed annually

4. Biomechanics The ACL functions as the primary restraint to anterior translation of the tibia and a secondary restraint to tibial rotation and to varus/valgus stress The ACL functions as the primary restraint to anterior translation of the tibia and a secondary restraint to tibial rotation and to varus/valgus stress Ultimate tensile load measured up to 2160 N and stiffness of 242 N/mm Ultimate tensile load measured up to 2160 N and stiffness of 242 N/mm It may tolerate strain of about 20% before failing It may tolerate strain of about 20% before failing

5. Response to Injury ACL lacks ability to regain functional integrity after conservative treatment post-injury ACL lacks ability to regain functional integrity after conservative treatment post-injury Therefore, if a patient wishes to regain near-full functional stability surgical ACL reconstruction is needed Therefore, if a patient wishes to regain near-full functional stability surgical ACL reconstruction is needed

6. The Older method: Autograft Reconstruction Currently, the most common graft choice for arthroscopic ACL reconstruction is the bone- patellar tendon-bone (BPTB) autograft Currently, the most common graft choice for arthroscopic ACL reconstruction is the bone- patellar tendon-bone (BPTB) autograft –Other sources: hamstring, semitentinosis, gracillis and the iliotibial band Reference of standard for restoring functional knee stability with 85-95% success rate Reference of standard for restoring functional knee stability with 85-95% success rate Return to physical activity 6 months postoperatively Return to physical activity 6 months postoperatively

7. Autograft: What’s the problem? Often associated with significant morbidity including: Often associated with significant morbidity including: –quadriceps weakness –patellofemoral pain –loss of motion –early degenerative changes Prepared bone-patellar tendon-bone autograft with marked bone-tendon junction. Busam and Rue (2007)

8. What’s the Alternative? ACL reconstruction with allograft tissue ACL reconstruction with allograft tissue A prepared bone-patellar tendon-bone allograft with marked bone-tendon junction. Busam and Rue (2007)

9. Allograft ACL Reconstruction Taken from cadavers Taken from cadavers Thought to have advantage of: Thought to have advantage of: –no donor-site morbidity –larger predictable graft sizes –low incidence of arthrofibrosis –shorter operative time

10. What’s the problem now? Allograft ACL reconstruction has been associated with complications, including: Allograft ACL reconstruction has been associated with complications, including: –High cost –Slower incorporation/recovery –Bacterial, viral and prion disease transmission –Lower stability rates

11. Literature Analysis Meunier, Odensten and Good (2007) Meunier, Odensten and Good (2007) –Performed randomized controlled trial involving 100 patients randomly allocated to primary reconstruction of an ACL rupture with an autograft or non-surgical treatment –Upon 15-year follow-up, found that those patients who were not treated surgically experienced significantly more problems with instability, meniscus injuries and development of osteoarthritis  2/3 of patients who did not initially undergo surgical repair ended up getting a surgical repair due to instability –Conclusion: early ACL reconstruction with an autograft improves knee stability and decreases the likelihood for meniscus injury and early development of osteoarthritis

12. Literature Analysis Lebel et al., (2008) Lebel et al., (2008) –Investigated the 10-year follow-up of 101 patients who received autograft ACL reconstruction specifically using a bone-patellar tendon-bone (BPTB) autograft –International Knee Documentation Committee (IKDC) score was statistically correlated to laxity, time of injury and osteoarthritis development –Overall, the researchers found that 70 out of the 101 patients, average age 28, were still actively participating in sports and ACL reconstruction using BPTB autograft resulted in high patient satisfaction levels and good clinical results 10 years post-op –Researchers also found that ACL reconstruction with BPTB autograft protected patients from secondary meniscus tears

13. Literature Analysis Orenzi et al. (2007) Orenzi et al. (2007) –Performed retrospective clinical study assessing morbidity via proprioreceptive differences and differences in laxity between autograft and allograft ACL reconstruction –Found that there is no significant difference in comparing autograft to allograft ACL reconstruction according to proprioreceptive measurements, and furthermore, proprioreception is not correlated to postoperative anterior knee laxity

14. Literature Analysis Prodromos, Joyce and Shi (2007) Prodromos, Joyce and Shi (2007) –Conducted a meta-analysis assessing the stability of autografts as compared to allografts for ACL reconstruction using the IKDC stability criteria  a side-to-side difference of less than or equal to 2mm is normal, and a difference of greater than 5mm is classified as abnormal

15. Prodromos, Joyce and Shi (2007) Graft<2 mm (%)P >5mm (%)P Auto: all (56)725 Allo: all (19)59 <0.01 14 <0.01 Allo: no rad (17)63 <0.01 12 <0.01 Auto BPTB (32)666 Allo BPTB all (10)57 0.02 160.01 Allo BPTB no rad (8)62 <0.1 12 <0.01 Auto 4HS (24)774 Allo Sft Tx (9)64 <0.01 12 <0.01 Graft stability rates by subgroup

16. Literature Analysis Prodromos, Joyce and Shi (2007) Prodromos, Joyce and Shi (2007) – The significance level was set at P < 0.05 and a P-value above this threshold would indicate a lack of statistical significance. –The overall normal stability rate for all autografts was 72% as compared to 59% for all allografts –The authors also go on to mention a study which was performed which found significant deterioration of allograft tissue and stability rates 10 years after implantation

17. Prodromos, Joyce and Shi (2007)

19. Literature Analysis Cause Source Immunologic responseSchulte, Jackson FreezingCryolife Lack of cryopreservationCryolife Increased donor ageKurzweil Increased graft shelf timeSterling Subclinical infectionCarpenter Radiation sterilizationNoyes, Gorschewsky Possible causes of increased allograft clinical laxity and sources of additional information

20. Literature Analysis Gulotta and Rodeo (2007) Gulotta and Rodeo (2007) –Performed a meta-analysis on the biology of autograft and allograft healing in ACL reconstruction –Found that BPTB autografts have shown to offer the strongest healing potential due to their reliance on bone-to-bone healing, however are often associated with greater donor-site morbidity  Hamstring autografts have less donor-site morbidity but rely solely on tendon-to-bone healing which occurs very slowly which may cause graft pull-out or slippage resulting in instability or graft failure

21. Literature Analysis Gulotta and Rodeo (2007) Gulotta and Rodeo (2007) –Also evaluated allograft healing in ACL reconstruction, and how their incorporation and remodeling are slower making allografts more vulnerable to failure –Aside from slower healing, the authors found that at 6 months post-operatively, autografts demonstrate better restraints to anterior-posterior displacement, double the load-to-failure strength, a significant increase in the cross-sectional area of the graft and more small-diameter collagen fibrils than allografts likely due to the prolonged presence of an inflammatory response with allograft

23. Literature Analysis Poolman, et al. (2007) Poolman, et al. (2007) –Performed a meta-analysis comparing patient morbidity post-ACL reconstruction with either a BPTB or a hamstring autograft –Found that patients in general experienced significantly less anterior-knee pain with hamstring autografts (relative risk 0.49 (95% CI: 0.32-0.76; p=0.001, I2 = 0%)) while maintaining stability as tested with a Lachman test –In general, morbidity associated with autographs has steadily decreased since 1991 Biau, et al. (2006) Biau, et al. (2006) –Performed meta-analysis comparing patient morbidity post- ACL reconstruction with either a BPTB or a hamstring autograft –Found that hamstring autografts were associated with lower morbidity as compared to BPTB concerning anterior knee pain and kneeling

24. Literature Analysis Busam and Rue (2007) Busam and Rue (2007) –Reasons to consider allograft for ACL reconstruction over autograft:  Age greater than 40 years  radiologic evidence of mild degenerative joint disease  moderate patellofemoral crepitation or pain symptoms  petite stature  questionable quality of donor graft tissue  patient request for allograft tissue  multi-ligamentous injuries

25. Literature Analysis Busam and Rue (2007) Busam and Rue (2007) –In the case of graft-construct mismatch, the authors mention several options for salvage including recessing the femoral tunnel, using femoral suspension fixation to recess the graft further while avoiding the risk of graft laceration with an interference screw and rotating the graft by 540 degrees to shorten the graft 5-6mm –For a more significant mismatch, a free tibial bone block technique may be performed in which the tendon is resected from the bone plug and a Krackow suture is placed in the tendon. After the femoral side of the graft is secured, the bone plug is placed anterior to soft tissue within the tibial tunnel while tension is maintained on the graft and the bone plug to prevent dislodgement.

26. Literature Analysis Hantes et al. (2008) Hantes et al. (2008) –Performed a clinical study measuring contamination during autograft preparation in ACL reconstruction in patients age 18-38 –Two groups were randomly assigned to either a BPTB autograft group and a hamstring autograft group, all receiving standard antibiotic treatment pre/postoperatively –It was found that 12% of the patients in the BPTB group and 13% of the patients in the hamstring group had positive bacterial cultures (Staphylococcus majority) one hour post-op but remained asymptomatic –Conclusion: minimal contamination may occur in autograft ACL reconstruction without going on to cause infection

27. So, where does that leave us? Successful 10-15 year follow-up: Autograft Successful 10-15 year follow-up: Autograft Proprioreceptive differences: None Proprioreceptive differences: None Greater stability: Autograft Greater stability: Autograft Greater likelihood of infection: Allograft Greater likelihood of infection: Allograft Decreased donor-site morbidity: Allograft/Hamstring Autograft Decreased donor-site morbidity: Allograft/Hamstring Autograft Greater overall success rate: Autograft Greater overall success rate: Autograft

28. When it all boils down.. When young, athletic patients are facing ACL reconstruction and having to choose a graft choice, one of their main priorities is getting back to successfully playing their sport as soon as possible When young, athletic patients are facing ACL reconstruction and having to choose a graft choice, one of their main priorities is getting back to successfully playing their sport as soon as possible Patients receiving autografts are able to safely initiate aggressive physical therapy sooner than those receiving allograft Patients receiving autografts are able to safely initiate aggressive physical therapy sooner than those receiving allograft Early initiation of rehabilitation  Quicker return to sport  happy athletes! Early initiation of rehabilitation  Quicker return to sport  happy athletes!

29. Is allograft all that bad? No. Autograft may not be the best choice for all patients in need of ACL reconstruction Autograft may not be the best choice for all patients in need of ACL reconstruction Allograft may be a reasonable option for certain patient populations, including those with multi-ligamentous injury, questionable quality of donor graft tissue, etc. Allograft may be a reasonable option for certain patient populations, including those with multi-ligamentous injury, questionable quality of donor graft tissue, etc.

30. Better graft? Though there are several studies favoring one graft or another, one should be cautious when saying that one graft is “better” than another Though there are several studies favoring one graft or another, one should be cautious when saying that one graft is “better” than another Neither autograft nor allograft match the quality of the native ACL Neither autograft nor allograft match the quality of the native ACL Many factors must be taken into consideration: Many factors must be taken into consideration: –Surgeon choice –Patient choice –Patient receiving graft

31. Application Practitioners must be able to adequately counsel patients as to their options for ACL reconstruction Practitioners must be able to adequately counsel patients as to their options for ACL reconstruction Based upon this research, young, athletic patients with a complete ACL tear would highly benefit from a BPTB or hamstring autograft for reconstruction Based upon this research, young, athletic patients with a complete ACL tear would highly benefit from a BPTB or hamstring autograft for reconstruction

32. What needs to be done? MORE RESEARCH! MORE RESEARCH! In order to reliably compare the two options for ACL reconstruction, more up- to-date prospective, controlled clinical studies need be completed directly comparing autografts to allografts regarding post-operative infection rates, rehabilitation, knee stability and graft failure rates. In order to reliably compare the two options for ACL reconstruction, more up- to-date prospective, controlled clinical studies need be completed directly comparing autografts to allografts regarding post-operative infection rates, rehabilitation, knee stability and graft failure rates.

33. References Baer, Geoffrey S., MD, PhD; Harner, Christopher D., MD. (2007) Clinical Outcomes of Allograft Versus Autograft in Anterior Cruciate Ligament Reconstruction. Clinics in Sports Medicine. 26(4): 661-81 Retrieved January 19, 2009. Meunier, A.; Odensten, M. Good, L. (2007) Long-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up. AbstractPreview Find Similar Articles. Scandinavian Journal of Medicine & Science in Sports. 17(3): 230-7. Retrieved January 19, 2009. Long-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up.Abstract Find Similar ArticlesLong-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up.Abstract Find Similar Articles Lebel B; Hulet C; Galaud B; Burdin G; Locker B; Vielpeau C. (2008) Arthroscopic reconstruction of the anterior cruciate ligament using bone-patellar tendon-bone autograft: a minimum 10-year follow-up. The American Journal of Sports Medicine. 36(7): 1275-82. Retrieved January 19, 2009. Ozenci, A.; Inanmaz, Erkan; Ozcanli, Haluk; Soyuncu, Yetkin; Samanci, Nehir; Dagseven, Tufan; Balci, Nilüfer; Gur, Semih. (2007) Proprioceptive comparison of allograft and autograft anterior cruciate ligament reconstructions. Knee Surgery, Sports Traumatology, Arthroscopy, Vol. 15 Issue 12, p1432- 1437. Retrieved January 19, 2009. Proprioceptive comparison of allograft and autograft anterior cruciate ligament reconstructions.Proprioceptive comparison of allograft and autograft anterior cruciate ligament reconstructions. Prodromos, Chadwick; Joyce, Brian; Shi, Kelvin. (2007) A meta-analysis of stability of autografts compared to allografts after anterior cruciate ligament reconstruction. Knee Surgery, Sports Traumatology, Arthroscopy, Jul2007, Vol. 15 Issue 7, p851-856. Retrieved January 19, 2009. A meta-analysis of stability of autografts compared to allografts after anterior cruciate ligament reconstruction.A meta-analysis of stability of autografts compared to allografts after anterior cruciate ligament reconstruction. Gulotta, Lawrence V., MD; Rodeo, Scott A., MD. (2007) Biology of Autograft and Allograft Healing in Anterior Cruciate Ligament Reconstruction. Clinics in Sports Medicine. Elsevier Inc. 26(4): 509-24. Retrieved January 20, 2009. Busam, Matthew L., MD; Rue, John-Paul H., MD, LCDR, MC, USN; Bach, Bernard R. Jr., MD.(2007) Fresh- Frozen Allograft Anterior Cruciate Ligament Reconstruction. Clinics in Sports Medicine. Elsevier Inc. 26(4): 607-23. Retrieved January 20, 2009. Hantes, Michael E, MD; Basdekis, Georgios K, MD; Varitimidis, Sokratis E., MD; Giotikas, Dimitrios, MD; Petinaki, Efthimia, MD; Malizos, Konstantinos N. (2008) Autograft Contamination During Preparation for Anterior Cruciate Ligament Reconstruction. The Journal of Bone and Joint Surgery. 90: 760-4. Retrieved January 27, 2009. Schoderberbek, Robert J. Jr, MD; Treme, Gehron P.; Miller, Mark D., MD. (2007) Bone-Patella Tendon-Bone Autograft in Anterior Cruciate Ligament Reconstruction. Clinics in Sports Medicine. 26(4): 525-47. Retrieved January 27, 2009. Biau, D.J; Tournoux, C ; Katsahian, S. ; Schranz, P.J. ; Nizard, R.S..(2006) Bone-patellar tendon-bone autografts versus hamstring autografts for reconstruction of the anterior cruciate ligament: meta-analysis. BMJ. 332(7548):995-1001. Epub. Retrieved February 2, 2009. Poolman, R.W.; Earrokhyar, F; Bhandari. M.. (2007) Hamstring tendon autografts better than bone-patellar tendon-bone autografts in ACL reconstruction: a cumulative meta-analysis and clinically relevant sensitivity analysis to a previously published analysis. Acta Orthop. Vol 78(3):350-4. Epub. Retrieved February 2, 2009.

34. P1 in a nutshell: