A systematic review to evaluate exercise for anterior cruciate ligament injuries: does this approach reduce the incidence of knee osteoarthritis?

Figures & data

Table 1 Search strategy; 68 key words within four key terms (knee, osteoarthritis, anterior cruciate ligament, exercise)

Knee (5)	Osteoarthritis (11)	Anterior cruciate ligament (4)
1. Knee 2. Knee joint 3. Menisci, tibial 4. Patellofemoral joint 5. Superior tibiofibular joint	1. aOsteoarthrit* 2. Osteoarthritis, knee 3. Osteoarthrosis 4. Arthritis, degenerative 5. Cartilage 6. Cartilage, articular 7. Fibrocartilage 8. Menisci, tibial 9. Joint instability 10. Instability, joint 11. Laxity, joint	1. Anterior cruciate ligament 2. Cruciate ligament, anterior 3. Ligaments, articular 4. Medial collateral ligament, knee
Exercise (48)
1. Exercises 2. Exercise, physical 3. Exercises, physical 4. Physical exercise 5. Physical exercises 6. Exercise, isometric 7. Exercises, isometric 8. Isometric exercises 9. Isometric exercise 10. Exercise, aerobic 11. Exercises, aerobic 12. Aerobic exercise	13. Aerobic exercises 14. Exercise movement techniques 15. Movement techniques, exercise 16. Exercise movement technics 17. Pilates-based exercises 18. Exercises, Pilates-based 19. Pilates based exercises 20. Muscle stretching exercise 21. Muscle stretching exercises 22. Exercise, muscle stretching 23. Exercises, muscle stretching 24. Proprioceptive neuromuscular facilitation (PNF) stretching	25. Static stretching 26. Dynamic stretching 27. Isometric stretching 28. Active stretching 29. Passive stretching 30. Relaxed stretching 31. Static-active stretching 32. Static-passive stretching 33. Circuit-based exercise 34. Weight-lifting exercise program 35. Weight-lifting strengthening program 36. Weight-bearing exercise program	37. Weight-bearing strengthening program 38. Resistance training 39. Strength training 40. Rehabilitation 41. Exercise therapy 42. Physical therapy modalities 43. Physical therapy (specialty) 44. Physiotherapy 45. Physical therapy 46. Manipulation, orthopedic 47. Musculoskeletal manipulations 48. Kinesiology, applied

Note:

a The search term was specifically “osteoarthrit*” not osteoarthritis. This ensured that words such as osteoarthritic were also searched.

Table 2 Summary of studies included in review

Author (year); PEDro scale score	Sample information; length of follow-up; retention	Intervention; retention	Results summary
Giove et al^Citation13 6/11	Sample: n=24 M (24) Age (FU): 30.2±5.2 y Length of FU: time from rehabilitation to FU: 12.8±4.73 mo Time from I to FU: 44.25±48.91 mo	Intervention:  All treated with exercise program (minimum of 7 mo)	1. Radiographic (n=22; two patients refused radiographs)   No statistically significant differences between injured and healthy contralateral knees 13/22 injured knees, 7/22 contralateral knees had degenerative changes 2. Instability, range of motion and laxity   High percentage of participants had positive anterior drawer (neutral [96%], 15° (external rotation [79%]), and Lachman tests (96%)   No significant differences in ranges of motion between injured and contralateral knees 3. Muscle strength   No difference in strength between injured and contralateral knees, but quadriceps 12% stronger than hamstrings in injured limb and 15% stronger in contralateral limb (P=0.005) 4. Activity level   Of n=24 returning to activity: 3= preinjury level (no symptoms), 11= full activity (occasional symptoms), 8= limited activity (moderate to severe symptoms), 2= minimal participation
Hawkins et al^Citation22 2/11	Sample: n=40 M (31): W (9) Age (I): 22±13 y Length of FU: 45 (rng, 24–79 mo)	Intervention:  All treated with an exercise program  Late reconstruction (30%) Retention: 28/40 (nonoperative)  23/28 radiographs  28/28 interviewed and examined	1. Radiographic   10/23 had some degenerative changes   1/23 had moderate OA   4/23 had mild or minimal OA 2. Self-reported symptoms/rating   Participants reported instability/giving way (86%), adequate or fully functional (61%), participating in sports with little or no limitation (57%), no pain (46%) or mild pain with activity (36%), occasional or no swelling (89%)   Overall ratings good (12.5%), fair (57.5%), poor (30%)
Kannus and Jarvinen^Citation14 5/11	Sample: n=98 M (71): W (27) Age (I): 32±13 y  Injury from sport related trauma (48%) Length of FU: 8.0±2.3 y	Intervention:  All treated with exercise program (only initial operative procedure was meniscectomy)  Late ACL reconstruction (35%); during the FU period (20%) and at FU (15%) Retention: 90/98  Grade III injury (49/90)  Grade II injury (41/90)	1. Radiographic   Grade III: 70% had signs of OA (including osteophytes, subchondral sclerosis and joint space narrowing)   Grade II: 15% had signs of OA (similar changes to grade III) 2. Instability, range of motion and laxity   Grade III: 95% were severely (3+) or grossly (4+) unstable anteriorly (as per anterior drawer and Lachman tests)   Grade II: instability less severe but comparable frequency to Grade III 3. Muscle strength   Grade III: strength deficits – extension (20%±18%) and flexion (16%±15%)   Grade II: strength deficits – extension (6%±10%) and flexion (4%±8%) 4. Activity level   Grade III: 80% reduced activity level, 25% changed occupations due to knee symptoms; 40% sustained several re-injuries   Grade II: 66% had same preinjury activity level, 7% changed occupations; 15% sustained several re-injuries
Pattee et al^Citation21 3/11	Sample: n=68 M (37): W (12) Age (I): 27 (rng, 16–46 y) Length of FU: 67 (rng, 48–122 mo)	Intervention:  All treated with exercise program  Late ACL reconstruction (n=9, 18%) (excluded from analysis) Retention: 49/68  9 excluded from analysis  40/68 questionnaires  31/40 physical exam  20/31 radiographs	1. Radiographic (n=20/31)   35% showed normal radiographs, 50% had mild flattening of the femoral condyle, 15% had mild subchondral sclerosis and osteophytes, none had joint space narrowing 2. Instability, range of motion and laxity (n=31/40)   Physical exam: 87% had pivot shifts; all participants had positive Lachman tests   Clinical test (KT-1000): average of 3.1 mm greater anterior displacement compared to contralateral knee 3. Self-reported symptoms/rating (n=40)   Participants reported instability (65%), giving way (35%), pain (60%), and mild swelling (40%)
Daniel et al^Citation9 6/11	Sample: n=298 Age (I): (rng, 15–44 y; in 91% of participants) Sample at FU: n=292 M (204): W (88) Length of FU: 64 (rng, 46–113 mo)	Intervention: 1. Group 1: early stable, exercise (n=54) 2. Group 2: early unstable, exercise (n=147) 3. Group 3: early reconstruction (n=45) 4. Group 4: late reconstruction (n=46) Retention: 292/298  285/292 interviewed and examined  7/292 interviewed  231/292 radiographs  245/292 functional tests  263/292 motion measurements	208 knees underwent arthroscopy to verify tears; n=2 (1%) of unstable and n=9 (50%) of stable knees did not have tears  Reconstructed patients had higher incidence of meniscal surgery  49% of patients with an ACL injury had a meniscal tear 1. Radiographic (n=231/292) and bone scan (n=165/292)   Greater degenerative changes on both scans in operative groups   All scores were generally low; radiograph (5.8, rng 0–32; maximum possible score: 83), bone scan (8.6, rng 0–24; maximum possible score: 24) 2. Instability, range of motion and laxity   Difference between normal and injured knee in Group 1 significantly different from other groups (P<0.001) for KT-1000 tests, quadriceps active test and manual muscle test 89%–93% of Group 1, 16%–55% of Group 2, 33%–64% of Group 3 and 30%–61% of Group 4 had displacement measurements <3 mm, depending on the test 3. Standardized Subjective scores   Group 1 performed better one-legged hop compared to all other groups (P<0.05) 4. Self-reported symptoms/rating   No participant changed occupations, but sports participation reduced in all groups (44%–55%)   Group 1 had lower symptoms and impairments compared to all other groups
Fink et al^Citation12 5/11	Sample: n=113  No difference in sports participation or activity-related symptoms between groups (P>0.05) Sample at FUII: Operative  n=46  M (37): W (9)  Age (I): 33.6±8.0 y Exercise  n=25  M (18): W (7)  Age (I): 32.3±9.9 y Length of FU: First FU (FUI): 74.2±8.1 mo Second FU (FUII): 132.2±8.1 mo	Intervention:  Operative (n=72)  Exercise (n=41)  Late ACL reconstruction (n=2 between FUI and FUII) Retention:  Operative  FUI =72.2%;  FUII =63.9% (n=46)  Exercise  FUI =78.1%;  FUII =61% (n=25)	1. Radiographic   Mild-to-moderate degenerative changes were not different between operative and exercise groups (P>0.05) but did increase over time (preinjury to FUI and FUII) in both groups (P<0.05) 2. Instability, range of motion and laxity   KT-1000: greater side-to-side laxity (P<0.05) and higher increase over time (P<0.05) for exercise group compared to operative 3. Standardized Subjective scores   FUI and II – operative higher Lysholm and Orthopaedische Arbeitsgruppe Knie scores than exercise (P<0.05)  Note: FUI and FUII not different (P>0.05)   IKDC scores at FUII:   No patients scored “normal”   43.5% operative/4.3% exercise “nearly normal”   52.1% in operative group and 52.1% in exercise group were “abnormal”   4.3% operative/43.5% exercise “severely abnormal” 4. Muscle strength   Higher knee extensor torque (P<0.05) in contralateral limb of each group compared to injured limb   Similar knee flexor torque (P>0.05) between limbs of each group 5. Self-reported symptoms/rating   FUI and II – operative higher self-reported rating than exercise (P<0.05) 6. Activity level   Operative maintained higher activity level than exercise, but both groups reduced over time (P<0.05)   Higher percentage of operative group (P<0.05) could maintain occupation at preinjury level (95.6%) compared to exercise (73.9%)
Fithian et al^Citation19 5/11	Sample: n=287 Sample at FU: M (101): W (108) Age (FU): 39 (rng, 16–69 y) Length of FU: 6.6 (rng, 3–10 y)	Intervention:  Participants assigned to 1/3 groups based on initial knee stability testing and preinjury sports participation level: 1. High risk (n=55)  Early operative (n=31)  Early exercise (n=24) (n=18 no late operative [ACL reconstruction]) 2. Moderate risk (n=72)  Early operative (n=26)  Early exercise (n=46) [n=30 no late operative] 3. Low risk (n=82)  Early operative (n=6)  Early exercise (n=76) [n=65 no late operative] Note: “exercise” will indicate no early or late ACL reconstruction Retention:  210/287 at FU  1 excluded due to surgery received elsewhere; 11 injured nonindex knee (excluded from analysis that required comparisons to nonindex knee)	Low risk group had fewer later surgeries (16%) than moderate and high risk groups, collectively (33%; P=0.008) 1. Radiographic   Operative had higher prevalence of OA than exercise at lateral (39%/25%; P=0.03), patellofemoral (71%/57%; P=0.03) and anterior (18%/6%; P=0.004) joint spaces 2. Instability, range of motion and laxity   Pivot shift and Lachman test: operative had lower scores than exercise (P<0.001)   KT-1000: high risk (P=0.002), moderate risk (P=0.002), and low risk (P=0.04) had less manual maximum displacement than exercise in same risk groups 3. Standardized Subjective scores   Short Form-36 (SF-36): operative higher on all subscales compared to exercise   IKDC: operative had higher percentage of participants scored as normal or nearly normal (83%) compared to exercise (33%; P<0.001)   Lysholm score: operative higher score than exercise (P<0.05) 4. Activity level   Tegner score: all groups had reduced scores (P<0.001), early operative had higher scores than exercise (P<0.001) and late operative (P=0.007) 5. Self-reported symptoms/rating   Exercise group had higher instability rate (giving-way episodes) than operative (P=0.009)   Operative better able to walk (P=0.04) and climb (P=0.047), but had more difficulty kneeling (P=0.02) than exercise
Meunier et al^Citation20 7/11	Sample: n=100 Operative  n=44  M (33): W (11)  Age (I)= 22 (rng, 14–30 y) Exercise  n=56  M (35): W (21)  Age (I) = 21 (rng, 14–30 y) Length of FU:15±1 y	Intervention:  Operative (n=42)  Exercise (n=52)  Late ACL reconstruction (n=16, 31%) Retention:  Operative (42/44)  Exercise (52/56)	Meniscus injury prevalence lower in the operative group (12%) compared to exercise group (35%) (P=0.015) 1. Radiographic   No significant difference in OA prevalence between operative and exercise groups   50% showed OA changes after 15 y, but <10% showed severe OA changes 2. Instability, range of motion and laxity   Operative group had reduced range of motion (P=0.0013) but better knee stability (Lachman tests (P=0.02); KT-1000 (P=0.0018)) compared to exercise group 3. Standardized Subjective scores   Operative group had better Lysholm scores, but similar KOOS scores, compared to exercise group
Kostogiannis et al^Citation16 6/11	Sample: n=100 M (58): W (42) Age (FU): 42.1 (rng 30–57 y) Length of FU: 15 (rng, 13–20 y)	Intervention:  Randomly assigned to supervised neuromuscular training or self-monitored traditional training  After 6 weeks 49% of self-monitored training group were transferred to supervised  23% had undergone reconstruction at FU (time from injury to reconstruction =4 [rng, 0.5–11.5 y]) Retention:  67/100  M (40): W (27)	No differences between patients who underwent self-monitored or supervised rehabilitation 1. Standardized Subjective scores   KOOS score: Lower scores for those injured in contact sports compared to noncontact (P<0.05)   Lower scores compared to matched controls on all subscales except pain (P=0.06)   IKDC score: 15 y FU score 83.3 (rng, 39.1–100)   Significantly lower scores for those injured in contact sports, compared to noncontact (P=0.007)   Lysholm score: Postinjury scores similar at 1 y (96 [rng, 61–100]) and 3 y (95 [rng, 60–100]) 15 y FU score decreased to 86 (rng, 32–100; P<0.001) 2. Activity level   Tegner score: Score at injury (7, rng 3–9); 1 y postinjury (6, rng 2–9, P<0.001); 3 y postinjury (6, rng 3–9); 15 y FU (4, rng 1–7, P<0.001)   At 3 y postinjury, 60% of exercise group had same or higher activity level as preinjury
Neuman et al^Citation1 7/11	Sample: n=100 Age (I): 26±8 y M (58): W (42) Length of FU: 15.7±1.4 y	Intervention:  All subjects treated initially with activity modification and physical therapy without ACL reconstruction  Late ACL reconstruction (n=22, 23%) Retention rate: 94/100  93/100 KOOS  84/100 Lysholm  84/100 Tegner  79/100 radiographs	1. Radiographic   15% of participants developed tibiofemoral (TF) OA (all had meniscal surgery)   None of the participants that had no (or minor) meniscal tear developed TF OA (P<0.0001)   6/17 in operative group and 7/62 exercise group had TF OA (P=0.03)   No TF OA in n=4 of operative group that did not have major meniscal injury 2. Standardized Subjective scores   Lysholm Score: Higher score in exercise group compared to operative group (P=0.049)   IKDC: 92/100 participated in sports at time of injury, 44/79 continued to participate at 15 y FU (P<0.0001)   KOOS: Higher pain scores in participants who had meniscal surgery (P=0.042) and ACL reconstruction (P=0.035); lower scores in those with radiographic TF OA 3. Activity level   Tegner score: Rating reduced from 7 (at injury) to 4 (15 y FU)   Operative group had higher score than exercise (P=0.085)
Neuman et al^Citation17 5/11	Sample: n=100 Age (I): 26±8 y Length of FU: 15.7±1.4 y	Intervention:  All subjects treated initially with activity modification and physical therapy without ACL reconstruction  Late ACL reconstruction (n=22, 23%) Retention rate: 94/100  74/94 Laxity test, Radiographs  4/94 Laxity test only  5/94 radiograph only  11/94 interview	Radiographic results described in Neuman et al.^Citation1  At FU, 48% had meniscal surgery (18/22 operative group, 26/72 exercise group) 1. I nstability, range of motion and laxity   Pivot shift and Lachman test: Both exercise and operative showed improved stability from baseline to 15 y FU (P<0.0001)   Operative more stable (P=0.007) and lower pivot shift grade (P<0.001) than exercise KT-1000: Sagittal laxity correlated with Lachman (P=0.0001) and pivot shift (P=0.001) tests   Difference between injured and contralateral knees was 1.8±4.2 mm for operative group and 2.4±2.7 mm for exercise group (P=0.46)
Kessler et al^Citation5 6/11	Sample: n=109 M (68): W (41) Age (I): 30.7 (rng, 12.5–54.0 y) Length of FU: 11.1 (rng, 7.5–16.3 y)	Intervention:  Operative (n=60)  Exercise (n=49)	1. Radiographic   No OA present in 52% of participants at FU (45% in operative and 61% in exercise group)   Significantly greater risk of OA (≥ Grade II) in operative group (45%) compared to exercise group (24%) (P=0.03) 2. Instability, range of motion and laxity   KT-1000: Statistically significant difference between injured and contralateral knees for operative (3.9, rng 0–12 mm) and exercise (5.7, rng 0–16 mm) groups (P<0.05) 3. Standardized Subjective scores   IKDC: operative group had better scores at FU compared to exercise group (P=0.008) 4. Activity level   Tegner score: no difference present between groups (P>0.05)
Meuffels et al^Citation2 7/11	Sample: n=50 Operative  M (19): (6)  Age (FU) = 37.6±6.2 y Exercise  M (19): (6)  Age (FU) = 37.8±6.8 y Length of FU: 10 y	Intervention:  Operative (n=25)  Exercise (n=25)  Participants were matched for sex (P=1.0), age (P=0.808), BMI (P=0.443), and activity level (P=0.831)	68% of operative and 80% of exercise group had meniscal surgery by 10 y FU (P=0.333) 1. Radiographic   48% of operative group and 28% of exercise group had radiographic OA at FU (P=0.145) 2. Instability, range of motion and laxity   KT-1000: 17% of exercise group and 6% of operative group had maximum side-to-side differences >3 mm (P=0.002)   Pivot shift: 21% of exercise group and 5% of operative group had scores ≥1 (P<0.001) 3. Standardized Subjective scores   IKDC: no significant differences between groups for IKDC (P=0.442), Lysholm (P=0.683) or one-legged hop test (P=0.522) 4. Activity level   Tegner score: scores not significantly different between operative and exercise groups after ACL injury (P=0.420) or at FU (P=0.188)
Mihelic et al^Citation18 6/11	Sample: n=54 M (44): W (10) Operative  n=36  Age (I) = 25.3 y Exercise  n=18  Age (I) = 25.5 y Length of FU: 17–20 y	Intervention:  Operative (n=36)  Exercise (n=18)	1. Radiographic   Operative group: 50% had mild and 16.5% had severe OA   Exercise group: no participants had knees classified as normal and 56% had severe OA (P<0.05) 2. Instability, range of motion and laxity   Anterior drawer test: 83% of operative group and 16% of exercise treated group had normal/near normal knees   Patients with stable knees had better function and more sport activity 3. Standardized Subjective scores   Lysholm score: operative group had higher score (84.3) than exercise group (53.3) (P<0.05)   IKDC: operative group had higher score (83.15) than exercise group (64.6) (P<0.05) 4. Activity level   Tegner score: significantly lower activity level in exercise group compared to operative group after injury (P<0.05), but no difference prior to injury (P<0.05)
Streich et al^Citation7 6/11	Sample: n=126 Sample at FU: n=80 Operative  M (28): W (12)  Age (FU): 26±6.2 y Exercise  M (28): W (12)  Age (FU): 24±6.8 y Length of FU: Operative 15.4±0.76 y Exercise 15.2±0.69 y	Intervention:  Operative (n=40)  Exercise (n=40)  Participants were matched for age, sex, BMI and concomitant injuries (no statistically significant differences) Retention rate: 80/126  n=14 lost to follow-up  n=8 lost to graft rupture  n=6 lost to late reconstruction  n =18 lost to age, sex, BMI and concomitant injuries	Significantly higher rate of meniscal surgery in exercise group than operative group (P=0.028) 1. Radiographic   Significant difference in radiographic OA between initial assessment and FU for both groups (Wilcoxon test P<0.001); 62.5% of operative and 55% of exercise 2. Instability, range of motion and laxity   KT-1000: no statistically significant differences in anterior laxity at either   20° Flexion (P=0.389) or 60° Flexion (P=0.732)   Pivot shift: Better rotational stability in operative group compared to exercise group, but not statistically significant (Fisher exact test P=0.662)   Significant relationship between a positive pivot shift at FU and OA prevalence (P<0.001)   Range of motion: reduced flexion range of motion at FU for n=17 in the operative group (P<0.05) 3. Standardized Subjective scores   IKDC: no statistically significant differences between groups (P=0.066) 4. Activity level   Tegner score: significant decrease between preinjury and postinjury in both groups (P=0.036) but no difference between groups
Potter et al^Citation11 7/11	Sample: n=40 (42 knees) Operative  n=28  M (14): W (14)  Age (I): 35.1±8.2 y Exercise  n=14  M (4): W (10)  Age (I): 41.5±9.7 y Length of FU: yearly FU (to maximum of 11 y)	Intervention:  Operative (n=28)  Exercise (n=14)	1. Standardized Subjective scores   Short Form-36 (SF-36) scores: no significant differences between groups for physical (P=0.139) or mental (P=0.476)   IKDC scores: delayed return to function, but by 2 y exercise was comparable to operative 2. Activity levels   Activity of Daily Living scores: No significant differences between groups   Activity Rating Scale scores: 1 y: operative (8.5±5.7), exercise (1.3±1.5), ns (P=0.056)   2 y: operative (8.5±6.1), exercise (8.2±5.6)   3 y: operative (5.6±3.9), exercise (10.0±4.9), ns (P=0.088) 3. MRI   Across both groups, by 7–11 y postinjury, risk of cartilage loss compared to baseline was 50× greater for lateral femoral condyle, 30× for the patella and 19× for the medial femoral condyle   Significantly higher odds ratio effect for cartilage loss over medial tibial plateau in exercise group compared to operative group
Frobell et al^Citation4 9/11	Sample: n=121 M (88): W (32) Sample at FU: n=120 Operative  n=61  M (49): W (12)  Age (I): 26.4±5.1 y	Intervention:  Operative (n=61)  Exercise (n=59)  Late ACL reconstruction (n=30, 51%)	1. Radiographic   No statistically significant differences between operative, late reconstruction and exercise groups for tibiofemoral OA (P=0.25) or patellofemoral OA development (P=0.21)   23/58 (40%) of operative group, 7/29 (24%) of late reconstruction group and 5/26 (19%) of exercise group developed OA (tibiofemoral/patellofemoral) 2. Instability, range of motion and laxity   Operative group had significantly better knee instability compared to exercise: Lachman test (P<0.001); Pivot shift (P<0.001)
	Exercise  n=59  M (39): W (20)  Age (I): 25.8±4.7 y Length of FU: Operative  60 (95% CI, 59–61) mo Exercise  59 (95% CI, 57–60) mo	Retention: 120/121	3. Standardized Subjective scores   KOOS: no significant differences between groups (P=0.45)   Short Form-36 (SF-36) scores: no significant differences between groups: physical component (P=0.78), mental component (P=0.34) 4. Activity level   Tegner score: no significant differences between groups (P=0.73)
Neuman et al^Citation10 7/11	Sample: Cohort from Neuman et al.^Citation1,Citation17 n=32 M (17): W (15) Age (FU): 45 (rng, 35–61 y) Length of FU: 20.6 (rng, 18–23 y)	All treated with exercise program No radiographic OA (grade ≤1) at 16 y FU Compared to healthy reference group (n=24) matched for level of physical activity and BMI (M [14]: W [10]), Age: 25 y	1. MRI (dGEMRIC)   No significant differences in T1Gd (used to estimate cartilage quality) values between ACL injured and healthy control group (matched for physical activity and BMI) both medially (P=0.065) or laterally (P=0.31)   No difference in T1Gd values between participants with and without radiographic OA (grade ≤1) (P=0.85)   No significant difference in T1Gd values between participants with and without major medial (P=0.48) and lateral (P=0.41) meniscal injury in their respective sides 2. Standardized Subjective scores   KOOS: ACL injured participants had comparable results to healthy controls; with significantly higher values for pain (P=0.034) and ADL (P=0.0084) subscales

Abbreviations: ACL, anterior cruciate ligament; BMI, body mass index; IKDC, International Knee Documentation Committee; KOOS, Knee injury and Osteoarthritis Outcome Score; OA, osteoarthritis, n, number of participants; M, men; W, women; y, years; mo, months; rng, range; FU, follow-up; I, injury; ns, not significiant; dGEMRIC, delayed gadolinium-enhanced magnetic resonance imaging of cartilage; MRI, magnetic resonance imaging.

Table 3 Exercise intervention description in the included studies

Author (year)	Exercise intervention
Giove et al^Citation13	Muscle rehabilitation program targeting the quadriceps and hamstrings, including: isometric, isotonic and isokinetic exercises (at least 7 months)
Hawkins et al^Citation22	Physiotherapist supervised exercise program targeting the quadriceps and hamstrings
Kannus and Jarvinen^Citation14	Initial immobilization; isometric quadriceps exercises; rehabilitation (at least 6 months)
Pattee et al^Citation21	Exercise/rehabilitation program targeting the quadriceps and hamstrings (supervised 3–6 weeks; encouraged to continue)
Daniel et al^Citation9	Initial immobilization; home exercise of cycling, swimming, isotonic exercises targeting the hamstrings
Fink et al^Citation12	Home exercise program of cycling, swimming and strengthening exercises targeting the hamstrings
Fithian et al^Citation19	Initial range of motion and nonimpact closed chain strengthening; jogging and sport-specific exercise (6–12 weeks after injury); return to competitive sports (3 months after injury, if not symptomatic)
Meunier et al^Citation20	Rehabilitation program targeting strength and coordination
Kessler et al^Citation5	Rehabilitation program including: bracing (6 weeks), quadriceps and hamstring muscle exercises, proprioception exercises, no loaded flexion greater than 60° (6 weeks), return to sports (3 months, if not symptomatic), return to contact/pivoting sports (9 months, if not symptomatic)
Kostogiannis et al^Citation16 Neuman et al^Citation1,Citation10,Citation17	Either physiotherapist supervised neuromuscular training or self-monitored training; both programs targeted stability and mobility, strength, performance, muscle activation strategies, proprioception and postural control
Meuffels et al^Citation2	Swelling reduction and range of motion; quadriceps and hamstrings strengthening program (at least 3 months)
Mihelic et al^Citation18	Initial immobilization; rehabilitation program including: range of motion, quadriceps strengthening (2 months); activity modification
Streich et al^Citation7	Physiotherapist supervised neuromuscular based rehabilitation program targeting stability and mobility; closed chain kinetic exercises, activity level progression
Potter et al^Citation11	Standard rehabilitation program
Frobell et al^Citation4	Rehabilitation program consistent with literature consensus

Table 4 PRISMA 2009 checklist

Section/topic	Number	Checklist item	Reported on page number
Title
Title	1	Identify the report as a systematic review, meta-analysis, or both	1
Abstract
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number	1
Introduction
Rationale	3	Describe the rationale for the review in the context of what is already known	1,2
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS)	2
Methods
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (eg, web address), and, if available, provide registration information including registration number	N/A
Eligibility criteria	6	Specify study characteristics (eg, PICOS, length of follow-up) and report characteristics (eg, years considered, language, publication status) used as criteria for eligibility, giving rationale	2,3
Information sources	7	Describe all information sources (eg, databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched	2
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated	Table 1
Study selection	9	State the process for selecting studies (ie, screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis)	2
Data collection process	10	Describe method of data extraction from reports (eg, piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators	2
Data items	11	List and define all variables for which data were sought (eg, PICOS, funding sources) and any assumptions and simplifications made	2,3
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis	3
Summary measures	13	State the principal summary measures (eg, risk ratio, difference in means)	3
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (eg, I2) for each meta-analysis	N/A
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (eg, publication bias, selective reporting within studies)	N/A
Additional analyses	16	Describe methods of additional analyses (eg, sensitivity or subgroup analyses, meta-regression), if done, indicating which were prespecified	N/A
Results
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram	3
Study characteristics	18	For each study, present characteristics for which data were extracted (eg, study size, PICOS, follow-up period) and provide the citations	Table 2
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome-level assessment (Item 12)	11, Table 2
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group and (b) effect estimates and confidence intervals, ideally with a forest plot	Table 2
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency	N/A
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (Item 15)	13–15
Additional analysis	23	Give results of additional analyses, if done (eg, sensitivity or subgroup analyses, meta-regression [Item 16])	N/A
Discussion
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (eg, health care providers, users, and policy makers)	12,13
Limitations	25	Discuss limitations at study and outcome level (eg, risk of bias), and at review level (eg, incomplete retrieval of identified research, reporting bias)	13–15
Conclusion	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research	15
Funding
Funding	27	Describe sources of funding for the systematic review and other support (eg, supply of data); role of funders for the systematic review	N/A

Note: Reproduced from Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–249.31

Abbreviations: N/A, not applicable; PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.

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