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Outcome of bone–patellar tendon–bone vs hamstring tendon autograft for anterior cruciate ligament reconstruction

Abstract Background: Many systematic reviews have compared the short-term outcomes of anterior cruciate ligment (ACL)reconstruction with hamstring and patellar tendon autograft,but few differences have been observed. The purpose of this meta-analysis was to compare the medium-term outcome of bone–patellar tendon–bone and hamstring tendon autograft for anterior cruciate ligament reconstruction in terms of clinical function, knee stability, postoperativecomplications, and osteoarthritis changes. Methods: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and the Cochrane Library databases were searched from inception to November 2, 2019. This meta-analysis included only randomized controlled trials that compared BPTB and HT autografts for ACL reconstruction with a 5-year minimum follow-up. The Cochrane Collaboration's risk-of-bias tool was used to estimate the risk-of-bias for all included studies. RevMan 5.3 software was used to performed statistical analysis of the outcomes. Results: Fifteen RCTs, involving 1298 patients (610 patients in the BPTB group and 688 patients in the HT group) were included. In terms of clinical function, no significant difference was found in the objective International Knee Documentation Committee score (OR = 0.94, 95%CI: 0.64–1.37, P = .75), Lysholm knee score (MD = −2.26, 95%CI: −4.56 to 0.05, P = .06), return to preinjury activity level (OR = 1.01, 95%CI: 0.67–1.52, P = .96), and Tegner activity level (OR = 0.03, 95%CI: −0.36 to 0.41, P = .89). There was no statistically significant difference in the Lachman test (OR = 0.86, 95%CI: 0.5–1.32, P = .50), pivot-shift test (OR = 0.68, 95%CI: 0.44–1.06, P = .09), and side-to-side difference (MD = −0.32, 95%CI: −0.81 to 0.16, P = .19). As for postoperative complications and OA changes, there were no statistically significant difference in flexion loss (OR = 1.09, 95%CI: 0.47–2.54, P = .85) and OA changes (OR = 0.76, 95%CI: 0.52–1.10, P = .15), but we found significant differences in favor of the HT group in the domains of kneeling pain (OR = 1.67, 95%CI: 1.04–2.69, P = .03), anterior knee pain (OR = 2.90, 95%CI: 1.46–5.77, P = .002), and extension loss (OR = 1.75, 95%CI: 1.12–2.75, P = .01). There was a significant difference in favor of the BPTB group in the domain of graft failure (OR = 0.59, 95%CI: 0.38–0.91, P = .02). Conclusions: Based on the results above, HT autograft is comparable with the BPTB autograft in terms of clinical function, postoperative knee stability, and OA changes, with a medium-term follow-up. The HT autograft for ACL reconstruction carries a lower risk of complications, such as anterior knee pain, kneeling pain, and extension loss, but an increased incidence of graft failure. Patients should be informed of the differences when deciding on graft choice with their physician.


Introduction
Anterior cruciate ligament (ACL) injury is one of the most common orthopedic injuries, with an annual incidence of isolated injury of 68.6 per 100,000 person-years. [1] A long-term followup study showed that the risk of secondary meniscus tear (hazard ratio 18.0), osteoarthritis (OA, hazard ratio 14.2), and the need for total knee arthroplasty (hazard ratio 5.0) in patients without ligament reconstruction after ACL tear was significantly higher than in those without ACL tear. [2] Although there was no consensus on whether to choose conservative treatment or ACLR after ACL injury in many studies, [3,4] numerous young and active individuals still choose ACLR. Typically, bone-patellar tendonbone (BPTB) and hamstring tendon (HT) autografts are chosen for ACLR.
Historically, the BPTB autograft was the gold standard for ACLR, as it allowed proper bone-to-bone tunnel healing, involved a short fixation distance, and provided excellent biomechanical strength. [5] Some studies have shown that BPTB autograft had the advantage of appropriate size, high durability, a low level of laxity, a higher incidence of return to sport activity, and a low rate of revision. [6][7][8][9] However, many patients have complained about donor site diseases, such as anterior knee pain, kneeling pain, and extension loss. [9][10][11][12] In recent years, HT autografts have been increasingly more frequently used in ACLR [13] because of its lower short-term donor site morbidity. [14,15] However, compared to BPTB autografts, HT autografts could lead to delayed graft incorporation, a decrease in knee stability, and significant flexor torque deficiency. [16][17][18][19] Numerous RCTs have been conducted to analyze the relative merits of the two mentioned autografts, and a large amount of data published on this topic have been used for several metaanalyses. [9,14,11,15,20,21] However, most previously published meta-analyses did not investigate the use of BPTB and HT autografts for ACLR after a medium-term follow-up. Xie et al's meta-analysis included 12 RCTs and two prospective cohort studies that used a minimum of 5 years' follow-up, and finally concluded that ACL reconstruction with BPTB autografts resulted in increased anterior knee pain, kneeling pain, and incidence of OA, as compared with HT autograft. [22] Poehling-Monaghan et al [21] also reported a systematic review comparing BPTB and HT autografts for ACLR at a minimum of 5 years' follow-up, but two of the included studies were cohort studies, and finally concluded that the clinical outcomes scores were lower, and greater motion loss and higher rates of OA were seen in the BPTB group. The above meta-analysis included prospective cohort studies, which markedly increased the risk of heterogeneity arising from variations in study design. In addition, some studies observed that the prevalence of OA was higher in the BPTB group during the long-term follow-up, while others found that there was no difference in the prevalence of OA between the BPTB group and the HT group. [23][24][25][26] Therefore, this issue remains controversial. In recent years, several RCTs [27][28][29] have compared BPTB autografts and HT autografts for ACLR after a medium-term follow-up. Therefore, there was a need for a new meta-analysis that included more recent and high-quality RCT studies to provide the latest evidence for clinical decision-making. Therefore, this meta-analysis aimed to determine whether there are significant differences between BPTB autografts and HT autografts for ACLR in terms of the clinical function, knee stability, postoperative complications, and OA changes, by comparing RCTs with a minimum follow-up of 5 years.

Methods
All analyses were based on previous published studies, thus no ethical approval and patient consent are required. This study is based on the Cochrane review methods.

Search strategy
This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. [30] PubMed, Embase, and Cochrane Library databases were the three major electronic databases used for the literature search from inception to November 2, 2019. Before conducting the search, a systematic review registration was completed on April 28, 2020 using the PROSPERO International prospective register of systematic reviews (registration number CRD42020170821). "anterior cruciate ligament," "bone patellar tendon," "hamstring," were the key words used in different combinations, and the detailed search strategy is (ACL OR anterior cruciate ligament) AND (patella OR patellar OR bone patellar tendon OR bone patella tendon) AND (hamstring OR semitendinosus OR gracilis patellar tendon). Additional studies were identified by reviewing the reference lists in the pertinent articles. Bibliographies of all the relevant retrieved studies were scrutinized to identify additional studies. Two authors (Deng and Lu) independently implemented the literature search, study selection and data extraction, and the reasons for exclusion were recorded and discordance was resolved by discussion or a decision from the corresponding author (Zhao).

Selection criteria
The included studies were randomized controlled trials (RCTs) and that directly comparing BTPB graft and HT graft for primary ACLR. Studies should be required to be published to be English and to have a minimum of 5-year follow-up. Studies with a Level of Evidence I and II (based on the Oxford Centre for Evidence-Based Medicine, used by the American version of the Arthroscopy and Journal of Bone and Joint Surgery [31] ). Studies that reported data on 1. functional outcome-objective International Knee Documentation Committee score, Lysholm knee score, return to preinjury activity level, Tegner activity level; 2. stability parameters-Lachman test, pivot test, side-to-side difference; 3. postoperative complications-anterior knee pain, kneeling pain, failure of graft, loss of extension and flexion; and 4. radiograph evidence of osteoarthritis were considered to be eligible. The number of strands of the autografts and the fixation in the proximal and distal part were not limited. Excluded were non-English articles, allograft, in vitro, animal, or cadaveric studies, and systematic reviews and meta-analyses. When multiple studies existed utilizing the same patient population but reporting outcomes at different time points, the study with the longest follow-up was included in our review while the rest were excluded.

Data extraction
The following information was extracted from the enrolled articles: the first author, date of publication, level of evidence, number of patients, number of depletions, mean age, sex, duration of follow-up, strands of the HT, type of graft fixation. The primary outcome was functional outcomes, such as an objective International Knee Documentation Committee (IKDC) score, return to preinjury activity level, Lysholm knee score. Other indicators include stability parameters, such as side-to-side difference, pivot-shift test, Lachman test; postoperative complications, such as anterior knee pain, kneeling pain, extension loss, flexion loss, and graft failure (defined as graft rupture or revision ACLR); and radiographic evidence of osteoarthritis. OA diagnosis was based on radiographic criteria, regarding of the classification or grading scale, OA was defined as the presence of joint-space narrowing of grade 2 and above in the Kellgren and Lawrence classification, grade 1 and above in the Ahlbäck rating system, and grade C and above in the IKDC classification.

Quality assessment
The quality of included studies was appraised by using the Cochrane Collaboration's risk-of-bias tool, [32] which contains the following seven items: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias. Each of the above items was scored using three options: low risk, unclear risk, and high risk.

Statistical analysis
All data were analyzed using RevMan 5.3 (Cochrane Collaboration, Oxford, UK) software. The mean difference (MD) was used to compare continuous variables, such as the Lysholm knee score and side-to-side difference. The odds ratio (O ) was used for some continuous variables, such as return to preinjury activity level, objective IKDC score with grades C and D, pivot-shift test, Lachman test, anterior knee pain, kneeling pain, extension loss, flexion loss, and graft failure. All results were reported with 95% confidence intervals (95%CIs), and P values < .05 were considered to indicate statistical significance. I 2 statistics and chi-square tests were used to evaluate heterogeneity. We chose the randomeffects model if I 2 > 50% and P < .1, because such studies had substantial heterogeneity. Alternatively, we chose the fixedeffects model if I 2 < 50% and P > .1. Funnel plots were used to screen for potential publication bias.

Search
We initially searched 890 citations in the three databases and three citations were identified from other sources, of which 354 were excluded as duplicate articles. Screening the titles and abstracts of the remaining 539 citations, we excluded 514 citations, which were irrelevant to the topic of interest, or were not RCT or clinical studies, or were studies with follow-up of shorter than 5 years. The full text of the remaining 25 citations was analyzed by a senior author, and finally, 15 articles [23,24,[27][28][29][33][34][35][36][37][38][39][40][41][42] were included in the meta-analysis (Fig. 1). All 15 studies that compared clinical outcomes between BPTB and HT autografts for ACLR were RCTs. The characteristics of the 15 included studies are summarized in Table 1. Overall, 1298 patients (n = 610 in BPTB, n = 688 in HT groups) were enrolled. The mean follow-up ranged from 60 months to 204 months.

Publication bias
A funnel plot was created to assess if there was bias in this study. The funnel plot appeared mild asymmetrical, suggesting publication bias in the data (Fig. 16).

Discussion
The results of this meta-analysis indicated that, compared with BPTB autografts, HT autografts were associated with a decreased incidence of anterior knee pain, kneeling pain, and extension loss, but increased incidence of graft failure after ACLR in mediumterm follow-up. Differences in other measures were not statistically significant between the two types of autografts used for ACLR.
Although ACL reconstruction is a mature technology, there is still considerable controversy about which autograft provides the best results for ACLR. BPTB autografts raise concerns about donor site morbidity, including anterior knee pain, kneeling pain, patella fracture, and patellar tendon rupture. [42,43] In their review, Kartus et al [44] pointed out that 40% to 60% of patients reported various donor site problems after harvesting of the BPTB autograft. It has been reported that patella fracture and patellar tendon rupture after ACLR are quite rare (with an incidence of 0.4% to 1.3% and 0.18% to 0.25%, respectively), and are related to irregular surgical procedures, such as deep and irregular saw cutting, poor centralization during the harvest leading to the lateral or medial side being too thin. [43] However, anterior knee pain and kneeling pain were quite common after ACLR with BPTB autograft, and it has been reported that these pains are related to injury to the infrapatellar branches of the saphenous nerve during the operation; [43] In BPTB autografts,  www.md-journal.com their incidences were 52% and 65% at the 2-year follow-up, respectively, which was higher than the 17% and 35% incidences, respectively, of HT autograft. [42] It has been reported that the transplantation of b-tricalcium phosphate or autologous bone to the donor-site bone defects at the tibial and patellar tubercle can effectively reduce the occurrence of anterior knee pain and kneeling pain. [45,46] Additionally, the double-incision technique has been used to avoid injury of the saphenous nerve infrapatellar branches and to preserve the paratenon and the patellar tendon, which can also reduce the donor site morbidity   associated with BPTB. [47] Gaudot et al [48] used the doubleincision technique to reduce the frequency of anterior knee pain to 18% (as compared to 58% for the single-incision technique), but there was no significant difference in the degree of anterior knee pain between the two techniques. The results of this metaanalysis showed that the HT group had apparent advantages in anterior knee pain and kneeling pain during medium-term follow-up. The incidence of moderate or severe kneeling pain Figure 11. Forest plot of comparison of the postoperative anterior knee pain between the bone-patellar tendon-bone (BPTB) vs hamstring tendon (HT) autograft groups for anterior cruciate ligament reconstruction. Table 2 The specific conditions of extension loss and flexion loss in each study.
Several potential limitations of this study should be noted. First, the final clinical results may be affected by the differences in population heterogeneity, follow-up duration, follow-up loss, method of graft fixation, and postoperative rehabilitation regimen, but it is not possible to control these variables individually. Second, although the flexion torque after HT harvest is important in the discussion between choosing BPTB and HT autografts for ACLR, there have been few reports about this in the included studies, and the reported indicators are different, making it impossible to carry out a meta-analysis of flexion torque. Third, not all the studies use the same scale to  grade radiographic signs of OA and there was an apparent lack of reported data combining both clinical and radiological aspects of OA. More high-quality RCTs with long-term follow-up are needed to come to a definite conclusion in future.

Conclusions
Based on the results above, HT autograft is comparable with the BPTB autograft in terms of clinical function, postoperative knee stability, and OA changes, with a medium-term follow-up. The HT autograft for ACL reconstruction carries a lower risk of complications, such as anterior knee pain, kneeling pain, and extension loss, but an increased incidence of graft failure. Patients should be informed of the differences when deciding on graft choice with their physician.