We identified 6615 potentially eligible studies via extensive searches. By checking the titles and abstracts, 2732 duplicates and 3828 unqualified studies were removed. Then, according to the inclusion and exclusion criteria, 31 studies were excluded by reading full texts. Twenty-four eligible studies were included for the final statistical analysis [19–42]. Figure 1 shows the detailed screening process.
3.2. Characteristics of the Included Studies
Characteristics of the included studies are listed in Table 1. Ten RCTs [26, 27, 32–35, 38, 40–42] and 14 CSs [19–25, 28–31, 36, 37, 39] involving 2400 patients with ACL injuries (1339 patients in the early ACLR group and 1061 patients in the delayed ACLR group) were included and published from 2003 to 2022. The reported timing of early ACLR ranged from 1 week to 12 months after ACL injuries while the reported timing of delayed ACLR was at least 3 weeks after ACL injuries. Three weeks, 4 weeks, 6 weeks, 6 months, and 12 months after ACL injuries were considered as the cut-off values of early and delayed ACLR respectively according to the information from included studies. For example, when 3 weeks was considered as the cut-off value, the patients received early ACLR during 3 weeks after ACL injuries while the patients received delayed ACLR when the duration of ACL injuries was more than 3 weeks. The reported outcomes included the functional status (Lysholm score, IKDC score), the knee pain intensity (VAS score), the knee joint stability (Lachman test), and the safety indicators (incidence of meniscal injuries, chondral lesions and adverse events).
Table 1
Characteristics of included studies
First author | Publication year | Male number (%) | Mean Age (year) | Interventions | Injury-to-Surgery Interval | Sample size (T/C) | Graft Source | Design | Follow-up (month) | Outcomes |
T | C | T/C | T | C | T | C |
Ding [19] | 2022 | 38(93) | 44(94) | 30.15/28.46 | Early ACLR | Delayed ACLR | ≤ 3 weeks | ༞6 weeks | 41/47 | HA | RCS | 12 | 1, 2, 4, 5, 6 |
Zhang [20] | 2022 | 22(59) | 24(65) | 33.84/34.73 | Early ACLR | Delayed ACLR | ≤ 12 months | ༞12 months | 37/37 | NA | CS | 12 | 1, 2, 3 |
Forsythe [21] | 2021 | 115(48) | 87(62) | 34.3/35.8 | Early ACLR | Delayed ACLR | ≤ 6 months | ༞6 months | 239/140 | HA | RCS | 12 | 2 |
Kawashima [22] | 2021 | 38(57) | 15(45) | 46.9/46.9 | Early ACLR | Delayed ACLR | ≤ 12 months | ༞12 months | 67/33 | HA | RCS | NA | 6 |
Chen [23] | 2021 | 40(51) | 38(48) | 40.35/41.23 | Early ACLR + R | Delayed ACLR + R | ≤ 3 weeks | ༞3 weeks | 79/79 | NA | CS | 12 | 1, 2, 7 |
Chua [24] | 2021 | 19(66) | 19(66) | 26/26 | Early ACLR + R | Delayed ACLR + R | ≤ 3 weeks | ༞20 weeks | 29/29 | HA | RCS | 12 | 1 |
Fang [25] | 2021 | 12(48) | 9(45) | 39.32/35.90 | Early ACLR + R | Delayed ACLR + R | ≤ 4 weeks | ༞4 weeks | 25/20 | HA | CS | 6 | 1, 2, 3, 7 |
Han [26] | 2020 | 34(68) | 35(70) | 41.5/40.85 | Early ACLR | Early ACLR | ≤ 3 weeks | ༞3 weeks | 50/50 | HA | RCT | 6 | 1, 2 |
Li [27] | 2020 | 45(61) | 46(62) | 38.05/37.92 | Early ACLR + R | Delayed ACLR + R | ≤ 3 weeks | ༞3 weeks | 74/74 | HA | RCT | NA | 1, 2, 7 |
Hu [28] | 2020 | 26(58) | 25(63) | 42.69/43.74 | Early ACLR + R | Delayed ACLR + R | ≤ 3 weeks | ༞3 weeks | 45/40 | HA | RCS | 6 | 1, 2, 4, 7 |
Wu [29] | 2019 | 31(67) | 30(65) | 32.48/32.51 | Early ACLR | Delayed ACLR | ≤ 12 months | ༞12 months | 46/46 | NA | RCS | 12 | 1, 2, 3, 5, 6 |
Ma [30] | 2019 | 20(63) | 20(67) | 28.03/32.23 | Early ACLR + R | Delyed ACLR + R | ≤ 6 weeks | ༞18 weeks | 32/30 | HA | RCS | 24 | 1, 5, 6 |
Li [31] | 2019 | 21(57) | 27(69) | 29.3/31.5 | Early ACLR + R | Delyed ACLR + R | ≤ 6 weeks | ༞6 weeks | 37/46 | HA | CS | 30 | 1, 2, 4, 5, 6 |
Shu [32] | 2019 | 28(65) | 30(70) | 44.36/42.07 | Early ACLR + R | Delyed ACLR + R | ≤ 3 weeks | ༞6 weeks | 43/43 | HA | RCT | 24 | 4, 7 |
Wang [33] | 2019 | 31(78) | 32(80) | NA | Early ACLR + R | Delyed ACLR + R | ≤ 6 weeks | ༞6 weeks | 40/40 | HA | RCT | 12 | 1, 2, 7 |
Manandhar [34] | 2018 | 83(80) | 30.0 | Early ACLR + R | Delyed ACLR + R | ≤ 3 weeks | ༞6 weeks | 53/51 | HA | RCT | 6 | 2, 5, 6, 7 |
Eriksson [35] | 2018 | 47(69) | 23(70) | 27.7/26.1 | Early ACLR + R | Delyed ACLR + R | ≤ 1 week | ༞6 weeks | 33/35 | HA | RCT | 6 | 1, 5, 6 |
Hur [36] | 2017 | 35(73) | 36(84) | 30.1/30.0 | Early ACLR | Delyed ACLR | ≤ 3 weeks | ༞12 weeks | 48/43 | NA | CS | 24 | 1, 4, 5, 6 |
Wang [37] | 2017 | 16(64) | 15(60) | 40.44/40.23 | Early ACLR + R | Delyed ACLR + R | ≤ 4 weeks | ༞4 weeks | 25/25 | NA | CS | 6 | 1, 2 |
Chen [38] | 2015 | 15(56) | 11(39) | 29.4/31.9 | Early ACLR + R | Delyed ACLR + R | ≤ 6 weeks | ༞24 weeks | 27/28 | LARS | RCT | 12 | 1, 7 |
Anstey [39] | 2012 | 102(60) | 13(54) | 33.4/36.1 | Early ACLR | Delyed ACLR | ≤ 6 months | ༞6 months | 171/24 | NA | RCS | NA | 5 |
Raviraj [40] | 2010 | 25(49) | 26(54) | 31.6/31.2 | Early ACLR | Delyed ACLR | ≤ 2 weeks | ༞4 weeks | 51/48 | HA | RCT | 32 | 1, 5, 6, 7 |
Bottoni [41] | 2008 | 58(83) | 29(83) | 26.4/27.5 | Early ACLR | Delyed ACLR | ≤ 3 weeks | ༞6 weeks | 34/35 | NA | RCT | 12 | 1, 5, 6, 7 |
Meighan [42] | 2003 | 28(90) | 21.0 | Early ACLR | Delyed ACLR | ≤ 2 weeks | ༞8 weeks | 13/18 | HA | RCT | 12 | 7 |
T: Treatment group; C: Control group; ACLR: Anterior cruciate ligament reconstruction; R: Rehabilitation; HA: Hamstring autograft; LARS: Ligament advanced reinforcement system; NA: Not available; RCT: Randomized controlled trial; CS: Cohort study; RCS: Retrospective cohort study; 1: Lysholm score; 2: International knee documentation committee score; 3: Visual analogue scale; 4: Lachman test; 5: Incidence of meniscal injuries; 6: Incidence of chondral lesions; 7: Incidence of adverse events |
3.4. Primary Outcomes
3.4.1. Lysholm Score
Lysholm score was reported in 7 RCTs [26, 27, 33, 35, 38, 40, 41] and 11 CSs [19, 20, 23–25, 28–31, 36, 37].
When 3 weeks was considered as the cut-off value, the pooled result of 2 RCTs showed that early ACLR could not significantly improve the Lysholm score compared with delayed ACLR at 6 months after surgery (MD = 4.16, 95% CI: -8.78 to 17.10, P = 0.53, I2 = 92%, Fig. 3A). However, at 6 months after surgery, 1 CS [28] showed that early ACLR was more effective than delayed ACLR for increasing the Lysholm score (MD = 4.29, 95% CI: 0.72 to 7.86, P = 0.02, Fig. 3A). At 12 months postoperatively, 1 RCT [41] revealed that the Lysholm score was not significantly increased after early ACLR compared with delayed ACLR (MD = -2.80, 95% CI: -13.51 to 7.91, P = 0.61). The pooled result of 3 CSs also revealed no significantly difference in the Lysholm score (MD = 1.45, 95% CI: -2.00 to 4.89, P = 0.41, I2 = 58%, Fig. 3A) between two groups. In the sensitivity analysis, after removing 1 CS [23] which was not reported the type of graft, the pooled result was not changed significantly (MD = 0.44, 95% CI: -7.26 to 8.15, P = 0.91, I2 = 79%). There was no statistically significant difference in the Lysholm score between two groups at 24 months postoperatively (1 CS [36], MD = -1.80, 95% CI: -4.55 to 0.95, P = 0.20, Fig. 3A) and at 32 months postoperatively (1 RCT [40], MD = -1.10, 95% CI: -13.29 to 11.09, P = 0.86, Fig. 3A). The Lysholm score from 1 RCT [27] was not described in this study because the time point of measuring the Lysholm score was not reported.
When 4 weeks was considered as the cut-off value, the pooled result of 2 CSs showed that early ACLR was more effective than delayed ACLR for increasing the Lysholm score at 6 months postoperatively (MD = 11.73, 95% CI: 2.18 to 21.27, P = 0.02, I2 = 87%, Fig. 3B).
When 6 weeks was considered as the cut-off value, the result of 1 RCT [33] showed that the Lysholm score was significantly increased after early ACLR compared with delayed ACLR at 12 months after surgery (MD = 4.56, 95% CI: 0.85 to 8.27, P = 0.02). However, 2 CSs found the Lysholm score was not statistically different between the early ACLR group and the delayed ACLR group (MD = 3.66, 95% CI: -0.41 to 7.73, P = 0.08, at 24 months after surgery [30]; MD = 1.60, 95% CI: -0.10 to 3.30, P = 0.07, at 30 months after surgery [31]).
When 6 months was considered as the cut-off value, the result of 1 RCT [38] indicated that the Lysholm score was not statistically different between two groups at 12 months postoperatively (MD = 1.73, 95% CI: -0.67 to 4.13, P = 0.16).
When 12 months was considered as the cut-off value, the pooled result of 2 CSs indicated that patients receiving early ACLR had higher Lysholm scores than those receiving delayed ACLR at 12 months postoperatively (MD = 5.60, 95% CI: 3.87 to 7.33, P < 0.00001, I2 = 53%, Fig. 3C).
3.4.2. International Knee Documentation Committe Score
IKDC score was reported in 4 RCTs [26, 27, 33, 34] and 9 CSs [19–21, 23, 25, 28, 29, 31, 37].
When 3 weeks was considered as the cut-off value, the results of meta-analysis showed that the IKDC score was significantly increased at 6 months after early ACLR compared with delayed ACLR (Pooled 2 RCTs, MD = 3.50, 95% CI: 1.37 to 5.62, P = 0.001, I2 = 12%; 1 CS [28], MD = 3.33, 95% CI: 0.41 to 6.25, P = 0.03, Fig. 4A). At 12 months postoperatively, the pooled result of 2 CSs indicated that early ACLR could significantly improve the IKDC score compared with delayed ACLR (MD = 1.68, 95% CI: 0.38 to 2.97, P = 0.01, I2 = 0%, Fig. 4a). However, 1 RCT [27] was not included in the meta-analysis because the time point of measuring IKDC score was not reported.
When 4 weeks was considered as the cut-off value, the pooled result of 2 CSs found that early ACLR was associated with the significant improvement in the IKDC score compared with delayed ACLR at 6 months after surgery (MD = 14.27, 95% CI: 7.04 to 21.51, P = 0.0001, I2 = 74%, Fig. 4B).
When 6 weeks was considered as the cut-off value, 1 RCT [33] found that early ACLR was associated with the significant improvement in the IKDC score compared with delayed ACLR at 12 months after surgery (MD = 4.48, 95% CI: 0.74 to 8.22, P = 0.02). However, 1 CS [31] showed that early ACLR was not associated with the significant improvement in the IKDC score compared with delayed ACLR at 30 months after surgery (MD = 1.80, 95% CI: -0.34 to 3.94, P = 0.10).
When 6 months was considered as the cut-off value, the result of 1 CS [21] showed that early ACLR could significantly increase the IKDC score compared with delayed ACLR at 12 months postoperatively (MD = 9.51, 95% CI: 5.04 to 13.98, P < 0.0001).
When 12 months was considered as the cut-off value, the pooled result of 2 CSs showed that early ACLR could significantly increase the IKDC score compared with delayed ACLR at 12 months postoperatively (MD = 7.94, 95% CI: 5.02 to 10.86, P < 0.00001, I2 = 83%, Fig. 4C).
3.4.3. Visual Analogue Scale Score
Three CSs [20, 25, 29] reported the VAS score.
When 4 weeks was considered as the cut-off value, 1 CS [25] showed that early ACLR was significantly associated with the reduction in the VAS score compared with delayed ACLR at 6 months postoperatively (MD = -1.60, 95% CI: -2.15 to -1.05, P < 0.00001).
When 12 months was considered as the cut-off value, the pooled result of 2 CSs indicated that early ACLR was significantly associated with the reduction in the VAS score compared with delayed ACLR at 12 months postoperatively (MD = -0.70, 95% CI: -0.89 to -0.50, P < 0.00001, I2 = 0%, Fig. 5).
3.4.4. Positive Rate of Lachman Test
Positive rate of Lachman test was reported in 1 RCT [32] and 4 CSs [19, 28, 31, 36].
When 3 weeks was considered as the cut-off value, 3 CSs found the positive rate of Lachman test was not statistically different between the early ACLR group and the delayed ACLR group (MD = 1.07, 95% CI: 0.35 to 3.23, P = 0.91, at 6 months postoperatively [28]; MD = 0.43, 95% CI: 0.12 to 1.51, P = 0.19, at 12 months postoperatively [19]; MD = 0.77, 95% CI: 0.48 to 1.24, P = 0.28, at 24 months postoperatively [36]). Moreover, 1 RCT [32] showed that there was no significant difference between two groups at 24 months postoperatively (MD = 0.89, 95% CI: 0.38 to 2.09, P = 0.79).
When 6 weeks was considered as the cut-off value, 1 CS [31] showed that there was no significant difference in the positive rate of Lachman test between two groups at 30 months postoperatively (MD = 0.83, 95% CI: 0.15 to 4.70, P = 0.83).
3.5. Secondary Outcomes
3.5.1. Incidence of Meniscal Injuries
The incidence of meniscal injuries was reported in 4 RCTs [34, 35, 40, 41] and 6 CSs [19, 29–31, 36, 39].
When 3 weeks was considered as the cut-off value, the meta-analysis including 2 RCTs found that there was no significant difference in the incidence of meniscal injuries at 6 months postoperatively between early ACLR and delayed ACLR (RR = 1.03, 95% CI: 0.37 to 2.87, P = 0.95, I2 = 90%, Fig. 6). The incidence of meniscal injuries was not statistically different between two groups (1 CS [19], RR = 1.00, 95% CI: 0.74 to 1.35, P = 0.99, at 12 months postoperatively; 1 CS [36], RR = 0.83, 95% CI: 0.58 to 1.18, P = 0.30, at 24 months postoperatively; 1 RCT [40], RR = 1.02, 95% CI: 0.81 to 1.29, P = 0.86, at 32 months postoperatively). However, 1 RCT [41] found that early ACLR was associated with the significant decrease in the incidence of meniscal injuries compared with delayed ACLR at 12 months postoperatively (RR = 1.37, 95% CI: 1.08 to 1.74, P = 0.010).
When 6 weeks was considered as the cut-off value, 2 CSs showed no statistically significant difference in the incidence of meniscal injuries between early ACLR and delayed ACLR (RR = 0.81, 95% CI: 0.57 to 1.16, P = 0.25, at 24 months postoperatively [30]; RR = 0.96, 95% CI: 0.65 to 1.41, P = 0.82, at 30 months postoperatively [31]).
When 6 months was considered as the cut-off value, 1 CS [39] was not included in the meta-analysis because the time point of measuring the incidence of meniscal injuries was not reported.
When 12 months was considered as the cut-off value, 1 CS [29] showed that no statistically significant difference in the incidence of meniscal injuries was identified between patients receiving early ACLR and delayed ACLR at 12 months postoperatively (RR = 0.95, 95% CI: 0.86 to 1.06, P = 0.40).
3.5.2. Incidence of Chondral Lesions
The incidence of chondral lesions was reported in 4 RCTs [34, 35, 40, 41] and 6 CSs [19, 22, 29–31, 36].
When 3 weeks was considered as the cut-off value, the meta-analysis including 2 RCTs found that early ACLR did not significantly decrease the incidence of chondral lesions compared with delayed ACLR (RR = 0.91, 95% CI: 0.12 to 6.78, P = 0.93, I2 = 91%, Fig. 7). No statistically significant difference in the incidence of chondral lesions was identified between patients receiving early ACLR and delayed ACLR (1 RCT [41], RR = 1.85, 95% CI: 0.69 to 4.97, P = 0.22, at 12 months postoperatively; 1 CS [19], RR = 0.79, 95% CI: 0.54 to 1.16, P = 0.23, at 12 months postoperatively; 1 CS [36], RR = 0.67, 95% CI: 0.40 to 1.14, P = 0.14, at 24 months postoperatively; 1 RCT [40], RR = 0.88, 95% CI: 0.64 to 1.21, P = 0.43, at 32 months postoperatively).
When 6 weeks was considered as the cut-off value, 2 CSs showed no statistically significant difference in the incidence of chondral lesions between early ACLR and delayed ACLR (RR = 0.75, 95% CI: 0.42 to 1.33, P = 0.32, at 24 months postoperatively [30]; RR = 0.58, 95% CI: 0.26 to 1.27, P = 0.17, at 30 months postoperatively [31]).
When 12 months was considered as the cut-off value, the result of 1 CS [29] showed that early ACLR was associated with the significant decrease in the incidence of chondral lesions compared with delayed ACLR at 12 months postoperatively (RR = 0.69, 95% CI: 0.54 to 0.88, P = 0.002). However, 1 CS [22] was not included in the meta-analysis because the time point of measuring the incidence of chondral lesions was not reported.
3.5.3. Incidence of Adverse Events
The incidence of adverse events was reported in 8 RCTs [27, 32–34, 38, 40–42] and 3 CSs [23, 25, 28].
When 3 weeks was considered as the cut-off value, the meta-analysis including 2 CSs showed that early ACLR could significantly decrease the incidence of adverse events compared with delayed ACLR (RR = 0.30, 95% CI: 0.11 to 0.80, P = 0.02, I2 = 0%, Fig. 8). However, the pooled result of 6 RCTs found no significant difference in the incidence of adverse events between early ACLR and delayed ACLR (RR = 0.78, 95% CI: 0.45 to 1.34, P = 0.37, I2 = 43%, Fig. 8).
When 4 weeks was considered as the cut-off value, 1 CS [25] indicated that there was no significant difference in the incidence of adverse events between early ACLR and delayed ACLR (RR = 0.13, 95% CI: 0.02 to 1.02, P = 0.05).
When 6 weeks was considered as the cut-off value, 1 RCT [33] indicated that the incidence of adverse events was not statistically different between the early ACLR group and the delayed ACLR group (RR = 0.33, 95% CI: 0.01 to 7.95, P = 0.50).
When 6 months was considered as the cut-off value, 1 RCT [38] indicated that there was no significant difference in the incidence of adverse events between early ACLR and delayed ACLR (RR = 2.07, 95% CI: 0.20 to 21.56, P = 0.54).