Background
Methods
Research design
Study search
Inclusion and exclusion criteria
Outcome measures
Data extraction
Quality assessment
Results
Search results
Description of studies
Data analysis
Cerza et al., 2012 [22] | Filardo et al., 2012 [11] | Sanchez et al., 2012 [24] | Vaquerizo et al., 2013 [25] | Filardo et al., 2015 [23] | Raeissadat et al., 2015 [13] | Montañez-Heredia, et al. 2016 [14] | |
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Registered | Not recorded | Not recorded | Real Decreto 223/2004 | Real Decreto 223/2004 | ClinicalTrials.gov, NCT01670578 | IRCT20140121134 42N5 | ClinicalTrials.gov, NCT02448407 |
Subject enrollment date | September 2009–September 2010 | Not recorded | January 2008–November 2009 | Not recorded | 2009–2013 | Not recorded | January to March 2014 |
Country | Italy | Italy | Spain | Spain | Italy | Iran | Spain |
Conflict of interest | None | None | None | Not mentioned | Not mentioned | None | None |
No. of subjects (knees) | 120 (120) | 109 (109) | 176 (176) | 96 (96) | 183 (183) | 160 (160) | 55 (55) |
Sex: male, female | 53, 67 | 68, 41 | 85, 91 | 38, 58 | 112, 71 | 23, 116 | 21, 32 |
Mean age, yr | 66.4 | 56.5 | 59.8 | 63.6 | 55.34 | 58.79 | 63.9 |
BMI, kg/m2 | Not recorded | 26.5 | 28.0 | 30.9 | 25.7 | 27.68 | 29.7 |
Bilateral vs. unilateral knee injections | Unilateral | Unilateral | Unilateral | Unilateral | Unilateral | Unilateral | Unilateral |
Ultrasound-guided injections or not | Not mentioned | Not mentioned | Not mentioned | Not mentioned | Not mentioned | Not mentioned | No |
Study group 1 | 60 Patients | 54 Patients | 87 Patients | 48 Patients | 96 Patients | 87 Patients | 28 Patients |
Study group 2 | 60 Patients | 55 Patients | 89 Patients | 48 Patients | 96 Patients | 73 Patients | 27 Patients |
Baseline characteristic differences between groups | No differences | No differences | No differences | No differences | No differences except for age | No differences except for age, sex, WOMAC (pain, function) | No differences |
Radiographic classification | Kellgren-Lawrence | Kellgren-Lawrence | Ahlbäck | Kellgren-Lawrence | Kellgren-Lawrence | Kellgren-Lawrence | Kellgren-Lawrence |
Grade I: 25 | Average of grade | Grade I: 87 | Grade II: 32 | Average of grade | Grade I: 6 | Grade I: 7 | |
Grade II: 22 | 2.2 for PRP group and 2.1 for HA group | Grade II: 64 | Grade III: 47 | 2.0 for PRP group and 2.0 for HA group | Grade II: 91 | Grade II: 19 | |
Grade III: 13 | Grade III: 23 | Grade IV: 17 | Grade III: 75 | Grade III: 27 | |||
Grade IV: 28 | |||||||
Length of follow-up | 24 Weeks | 12 Months | 6 Months | 48 Weeks | 12 Months | 52 Weeks | 6 Months |
Outcome scores used | WOMAC | IKDC, Tegner, KOOS, EQ VAS | WOMAC, VAS | WOMAC, Lequesne, OMERACT-OARSI | IKDC, KOOS, EQ VAS, Tegner score | WOMAC, SF-36 | VAS, KOOS, EuroQol |
Prior surgeries | No | 63 Subjects | None in last year | Not recorded | 101 Subjects | Not recorded | No |
Prior injections | No | Not recorded | None in prior 6 months | None in prior 6 months | Conservative | None in prior 2 weeks | No |
PRP no. of injections | 4 | 3 | 3 | 3 | 3 | 2 | 3 |
PRP volume per Injection | 5.5 ml | 8 ml | 12 ml | 8 ml | 5 ml | 4–6 ml | 5 ml |
Injection interval, wk | 1 | 1 | 1 | 2 | 1 | 4 | 2 |
Injection approach | Superolateral | Not recorded | Superolateral | Superolateral | Not recorded | Anteromedial or lateral midpatellar | Not recorded |
Primary and secondary outcomes | WOMAC score before infiltration and at 4, 12, and 24 weeks after first injection | IKDC, EQ VAS, Tegner, and KOOS scores, range of motion and knee circumference changes were evaluated at 2, 6, and 12 months | WOMAC scores at 1, 2, and 6 months | WOMAC and Lequesne scores at 24 and 48 weeks | IKDC, KOOS, EQ VAS, and Tegner scores at baseline and then at 2, 6, and 12 months after last injection | WOMAC and SF-36 scores at 52 weeks | VAS, KOOS, EuroQol following the third infiltration and after 3 and 6 months following final infiltration |
Study | Adverse events |
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Cerza et al. [22] | No adverse reactions. None were observed in our series. |
Filardo et al., 2012 [11] | Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (P = 0.039). However, this reaction was self-limiting within a few days and did not compromise the overall outcome. |
Sanchez et al.. [24] | Adverse events were generally mild and evenly distributed between the groups (P < 0.811). Most of these adverse events (96% in the PRGF-Endoret® group and 92% in the HA group) were not related to the type of treatment. |
Vaquerizo et al. [25] | Sixteen adverse events, 8 in the PRGF-Endoret® group and 8 in the HA group, were reported during the study. Adverse events were generally mild and evenly distributed between the groups (P = 0.610). Seven of 8 adverse events in the HA group and all the events in the PRGF-Endoret® group were related to pain associated with the infiltration. |
Filardo et al., 2015 [23] | Two patients reported severe pain and swelling after HA injections, while no major adverse events were noted in the PRP group. However, PRP presented overall significantly more postinjection swelling and pain. |
Raeissadat et al.......... [13] | The present authors had previously performed studies to evaluate the clinical application of PRP, and recorded safety and positive findings. It was a prospective study published in 2013 on 60 patients treated with two injections of PRP (1 every 4 weeks). |
Montañez-Heredia et al. [14] | Adverse events relating to infiltration were infrequent, mild and appeared immediately, and their distribution between both groups did not show significant differences. There was pain related to infiltration in nine of 27 PRP injections and in four of 26 for HA, but only one patient (in PRP group) had transitory swelling that resolved itself. No relationship between these events and the growth factor or blood cell composition of PRP was found. |
Study | Pretreatment | Early (0–6 wk) | Middle (6–12 wk) | Late (12–26 wk) | Extended (26–52 wk) |
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Cerza et al. [22] | ACP: WOMAC 76.9 ± 9.5 | ACP: WOMAC 49.6 ± 17.7 ES: 2.8 | ACP: WOMAC 39.1 ± 17.8 | ACP: WOMAC 36.5 ± 17.9 | DNC |
HA: WOMAC 55.2 ± 12.3 | ES: 4.0 | ES: 4.3 | |||
HA: WOMAC 75.4 ± 10.7 | ES: 1.9 (P < 0.001) between groups | HA: WOMAC 57 ± 11.7 | HA: WOMAC 65.1 ± 10.6 | ||
ES: 1.7 (P < 0.001) between groups | ES: 1.0 (P < 0.001) between groups | ||||
Filardo et al. [11] | PRP: IKDC score 50.2 ± 15.7 | DNC | PRP: IKDC score 62.8 ± 17.6 ES: 0.8 | PRP: IKDC score 64.3 ± 16.4 ES: 0.9 | PRP: IKDC score 64.9 ± 16.8 ES: 0.9 |
KOOS symptoms 64.0 ± 17.9 | KOOS symptoms 71.9 ± 17.0 ES: 0.4 | KOOS symptoms 73.0 ± 18.3 ES: 0.5 | KOOS symptoms 71.3 ± 17.9 ES: 0.4 | ||
Pain 65.4 ± 17.7 | Pain 71.9 ± 17.0 ES: 0.4 | Pain 74.2 ± 19.6 ES: 0.5 | Pain 74.0 ± 19.4 ES: 0.5 | ||
ADL 69.9 ± 20.0 | ADL 81.2 ± 17.9 ES: 0.6 | ADL 79.1 ± 19.0 ES: 0.5 | ADL 77.9 ± 20.6 ES: 0.4 | ||
Sport 37.6 ± 24.7 | Sport 48.8 ± 25.9 ES: 0.5 | Sport 48.7 ± 29.5 ES: 0.5 | Sport 47.4 ± 28.2 ES: 0.4 | ||
QOL 34.9 ± 18.8 | QOL 48.8 ± 25.9 ES: 0.7 | QOL 48.0 ± 23.1 ES: 0.7 | QOL 50.5 ± 22.6 ES: 0.8 | ||
Tegner score 2.9 ± 1.4 | Tegner score 3.8 ± 1.3 ES: 0.6 | ||||
HA: IKDC score 47.4 ± 15.7 | HA: IKDC score 61.4 ± 16.2 | HA: IKDC score 61.0 ± 18.2 | HA: IKDC score 61.7 ± 19.0 | ||
ES: 0.9 | ES: 0.9 | ES: 0.9 | |||
KOOS | KOOS | KOOS | KOOS | ||
Symptoms 67.8 ± 15.7 | Symptoms 71.6 ± 16.3 ES: 0.2 | Symptoms 74.3 ± 16.0 ES: 0.4 | Symptoms 74.2 ± 17.5 ES: 0.4 | ||
Pain 63.1 ± 17.4 | Pain 71.1 ± 18.6 ES: 0.5 | Pain 73.2 ± 18.1 ES: 0.6 | Pain 74.0 ± 19.4 ES: 0.6 | ||
ADL 67.8 ± 21.0 | ADL 78.2 ± 17.4 ES: 0.5 | ADL 77.3 ± 18.6 ES: 0.5 | ADL 77.3 ± 19.8 ES: 0.5 | ||
Sport 34.2 ± 23.9 | Sport 45.0 ± 24.1 ES: 0.5 | Sport 44.7 ± 27.8 ES: 0.5 | Sport 46.6 + −27.9 ES: 0.5 | ||
QOL 33.6 ± 18.0 | QOL 45.5 ± 23.9 ES: 0.7 | QOL 48.5 ± 24.7 ES: 0.8 | QOL 49.2 ± 26.0 ES: 0.9 | ||
Tegner score 2.6 ± 1.2 | Tegner score 3.4 ± 1.6 ES: 0.7 | ||||
P values not recorded | |||||
Sanchez et al. [24] | PRGF: WOMAC | DNC | DNC | PRGF: WOMAC 74.0 ± 42.7 ES: 1.1 | DNC |
121.8 ± 44.4 | 38.2% of patients had 50% decrease in WOMAC pain score 57.3% of patients had 20% decrease in WOMAC pain score | ||||
Lequesne 9.5 ± 3.0 | Lequesne 5.2 ± 3.4 ES: 1.4 | ||||
HA: WOMAC | HA: WOMAC 78.3 ± 48.1 | ||||
115.6 ± 45.1 | ES: 0.8 | ||||
24.1% of patients had 50% decrease in WOMAC pain score, 52.9% of patients had 20% decrease in WOMAC pain score | DNC | ||||
Lequesne 9.1 ± 3.2 | Lequesne 5.4 ± 3.3 ES: 1.2 | ||||
Differences between PRGF and HA for 50% decrease in WOMAC pain score (P = 0.044), for 20% decrease (P = 0.555), for total WOMAC score (P = 0.561), and for Lequesne score (P = 0.714) | |||||
Vaquerizo et al. [25] | PRGF: WOMAC 45.9 ± 12.7 Lequesne 12.8 ± 3.8 HA: WOMAC 50.8 ± 18.4 Lequesne 13.1 ± 38 | DNC | DNC | For patients with 30% decrease in: WOMAC summed score: rate of response of PRGF was 66, 43, and 23 percentage points higher than that of HA for pain, physical function and stiffness, respectively (P < 0.001, P < 0.001, P = 0.02, respectively). Lequesne score: PRGF group is 56 percentage points higher than HA group (P < 0.001) For patients with 50% decrease in: WOMAC summed score: rate of response of PRGF was 43, 29, and 19 percentage points higher than that of HA for pain, physical function and stiffness, respectively (P < 0.001, P = 0.001, P = 0.035, respectively). Lequesne score: PRGF group is 25 percentage points higher than HA group (P = 0.002) | For patients with 30% decrease in: WOMAC summed score: rate of response of PRGF was 46, 37, and 40 percentage points higher than that of HA for pain, physical function and stiffness, respectively (P < .001, P < .001, P < 0.001, respectively). Lequesne score: PRGF group 46 percentage points higher than HA group (P < 0.001) For patients with 50% decrease in: WOMAC summed score: rate of response of PRGF was 29, 31, and 28 percentage points higher than that of HA for pain, physical function and stiffness, respectively (P < 0.001, P < 0.001, P = 0.001, respectively). Lequesne score: 19 and 2 percentage points in the PRGF and HA groups, respectively |
Filardo et al. [23] | PRP: IKDC score 52.4 ± 14.1 | DNC | PRP: IKDC score 63.2 ± 16.6 ES: 0.8 | PRP: IKDC score 65.0 ± 16.1 ES: 0.9 | PRP: IKDC score 66.2 ± 16.7 ES: 1.0 |
KOOS Symptoms 65.5 ± 16.6 | KOOS Symptoms 72.9 ± 17.0 ES: 0.4 | KOOS Symptoms 74.7 ± 16.9 ES: 0.6 | KOOS Symptoms 73.9 ± 17.2 ES: 0.5 | ||
Pain 66.1 ± 17.9 | Pain 73.8 ± 19.9 ES: 0.4 | Pain 74.7 ± 19.3 ES: 0.5 | Pain 74.9 ± 19.3 ES: 0.5 | ||
ADL 70.6 ± 19.4 | ADL 79.0 ± 19.8 ES: 0.4 | ADL 79.1 ± 19.6 ES: 0.4 | ADL 78.4 ± 20.7 ES: 0.4 | ||
Sport 37.9 ± 25.0 | Sport 48.0 ± 26.1 ES: 0.4 | Sport 49.6 ± 28.6 ES: 0.5 | Sport 49.3 ± 28.6 ES: 0.5 | ||
QOL 36.0 ± 19.4 | QOL 48.4 ± 23.1 ES: 0.6 | QOL 49.2 ± 23.4 ES: 0.7 | QOL 50.8 ± 24.0 ES: 0.8 | ||
EQ VAS score 73.2 ± 12.0 | EQ VAS score 76.3 ± 12.7 | EQ VAS score 76.2 ± 12.9 | EQ VAS score 77.6 ± 11.1 | ||
ES: 0.3 | ES: 0.3 | ES: 0.4 | |||
Tegner score 2.9 ± 1.3 | Tegner score3.6 ± 1.4 ES: 0.5 | Tegner score 3.7 ± 1.5 ES: 0.6 | Tegner score 3.7 ± 1.3 ES: 0.6 | ||
ROM 129.6 ± 12.2 | ROM 130.6 ± 11.8 | ROM 130.3 ± 10.7 | ROM 130.2 ± 11.1 | ||
TPC 410.0 ± 34.3 | TPC 411.4 ± 35.2 | TPC 407.2 ± 35.6 ES: 0.1 | TPC 402.3 ± 33.4 ES: 0.1 | ||
HA: IKDC score 49.7 ± 13.0 | HA: IKDC score 63.5 ± 15.2 ES: 0 | HA: IKDC score 63.5 ± 17.1 ES: 0 | HA: IKDC score 64.2 ± 18.0 ES: 0 | ||
KOOS Symptoms65.8 ± 16.3 | KOOS Symptoms 70.9 ± 16.6 ES: 0.3 | KOOS Symptoms 72.7 ± 17.4 ES: 0.4 | KOOS Symptoms73.9 ± 18.4 ES: 0.5 | ||
Pain 64.1 ± 16.5 | Pain 72.6 ± 17.9 ES: 0.5 | Pain74.8 ± 17.6 ES: 0.7 | Pain 75.4 ± 19.0 ES: 0.7 | ||
ADL 68.2 ± 20.2 | ADL 78.0 ± 17.9 ES: 0.5 | ADL78.4 ± 18.6 ES: 0.5 | ADL 78.4 ± 19.3 ES: 0.5 | ||
Sport 35.7 ± 24.6 | Sport 44.0 ± 25.5 ES: 0.3 | Sport 45.1 ± 27.0 ES: 0.4 | Sport 46.3 ± 28.1 ES: 0.4 | ||
QOL 35.7 ± 18.2 | QOL 47.7 ± 22.1 ES: 0.7 | QOL 49.9 ± 23.1 ES: 0.8 | QOL 50.9 ± 24.4 ES: 0.8 | ||
EQ VAS score 71.6 ± 13.4 | EQ VAS score 73.9 ± 13.7 ES: 0.2 | EQ VAS score74.1 ± 15.1 ES: 0.2 | EQ VAS score 73.4 ± 15.2 ES: 0.1 | ||
Tegner score 2.8 ± 1.3 | Tegner score3.3 ± 1.5 ES: 0.4 | Tegner score 3.5 ± 1.5 ES: 0.5 | Tegner score 3.4 ± 1.5 ES: 0.5 | ||
ROM 128.2 ± 12.2 | ROM 129.0 ± 10.9 | ROM 128.0 ± 11.4 | ROM 127.4 ± 12.0 | ||
TPC 415.0 ± 34.7 | TPC 413.3 ± 34.1 | TPC 408.7 ± 32.5 | No statistical significance between groups | ||
No statistical significance between groups | No statistical significance between groups | No statistical significance between groups | |||
Raeissadat et al. [13] | PRP: WOMAC 39.5 ± 17.06 | DNC | DNC | DNC | PRP: WOMAC 18.44 ± 14.35 (P < 0.001) ES: 1.2 |
Pain 8.46 ± 4.17 | Pain 4.03 ± 3.36 (P < 0.001) ES: 1.1 | ||||
Physical function 2.2 ± 1.76 | Physical function 1.19 ± 1.4 (P < 0.001) ES: 0.6 | ||||
Stiffness 28.91 ± 12.63 | Stiffness 13.19 ± 10.39 (P < 0.001) ES: 1.2 | ||||
SF-36 (PCS) 178.14 ± 81.0 | SF-36 (PCS) 255.96 ± 77.59 (P < 0.001) ES: 1.0 | ||||
SF-36 (MCS) 229.22 ± 95.62 | SF-36 (MCS) 269.92 ± 91.48 (P < 0.001) ES: 0.4 | ||||
HA: WOMAC 28.69 ± 16.69 pain 6.91 ± 3.82 physical function 1.88 ± 1.72 stiffness 19.88 ± 12.32 SF-36 (PCS) 180.4 ± 68.52 SF-36 (MCS) 226.43 ± 97.39 | HA: WOMAC 27.46 ± 16.36 (P = 0.78) pain 5.08 ± 3.71 (P = 0.029) ES: 0.5 physical function 2.14 ± 1.66 (P = 0.16) stiffness 19.51 ± 11.9 (P = 0.919) SF-36 (PCS) 189.39 ± 103.73 (P = 0.37) SF-36 (MCS) 216.91 ± 100.9 (P = 0.74) ES: 0.1 | ||||
Montañez-Heredia et al. [14] | DNC | PRP: EQ Worsening 7.4% | DNC | PRP: EQ Worsening 3.7% | PRP: EQ Worsening 7.4% |
Similar 74.1% | Similar 48.1% | Similar 48.1% | |||
Improvement 18.5% | Improvement 48.1% | Improvement 44.4% | |||
50% decrease VAS: 55.5% | 50% decrease VAS: 55.5% | 50% decrease VAS: 44.4% | |||
HA: EQ Worsening 0% | HA: EQ Worsening 11.5% | HA: EQ Worsening 15.4% | |||
Similar 65.4% | Similar 53.8% | Similar 50.0% | |||
Improvement 34.6% | Improvement 34.6% | Improvement 34.6% | |||
50% decrease VAS: 57.7% | 50% decrease VAS: 30.7% | 50% decrease VAS: 42.3% | |||
KOOS: For patients with arthritis grade II, ADL at 3-month follow-up improved significantly on the KOOS scale in the PRP group as compared with the HA group (P = 0.040) | KOOS: At 6 months follow-up, pain decreased for arthritis grade II patients injected with PRP (P = 0.012) with improvements in function in daily living (P = 0.013) and function in sport and recreation (P = 0.021) |
Risk of bias
Discussion
Study | Leukocyte-poor/rich PRP | Fresh/frozen PRP |
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Cerza et al. [22] | Leukocyte-poor PRP | Frozen PRP |
Filardo et al. [23] | Leukocyte-rich PRP | Fresh PRP |
Sanchez et al. [24] | Leukocyte-poor PRP | Fresh PRP |
Vaquerizo et al. [25] | Leukocyte-poor PRP | Frozen PRP |
Filardo et al. [23] | Leukocyte-rich PRP | Frozen PRP |
Raeissadat et al. [13] | Leukocyte-rich PRP | Fresh PRP |
Montañez-Heredia et al. [14] | Leukocyte-poor PRP | Frozen PRP |