Keywords
low back pain - platelet-rich plasma - pain scores - systematic review - meta-analysis
Introduction
Low back pain is a common and devastating problem for patients and physicians, and
it results in high morbidity and a great economic burden.[1]
[2]
[3]
[4]
[5] Low back pain is the most common cause of disability of patients between 45 and
65 years of age.[6]
[7] Approximately 20% of patients have a recurrence within 6 months of the initial episode,
and some experience chronic symptoms. Numerous factors can cause low back pain including
intervertebral disk herniation and lumbar facet joint syndrome.[8]
[9]
[10]
[11]
Platelet-rich plasma (PRP) is an autologous biological blood-derived product and can
release high concentrations of platelet-derived growth factors to enhance the body's
natural healing response.[12]
[13] PRP also possesses antimicrobial properties and may have some ability to prevent
infections.[14]
[15] Local injection of PRP is reported to be an effective modality to reduce pain, disability,
and functional limitation, and to improve structural integrity and biomechanical strength
for various painful conditions including tendinopathy, muscle strain injury, ligament
injury, and knee osteoarthritis.[16]
[17]
[18]
[19]
[20]
[21] PRP was found to stimulate the metabolism of intervertebral disk cells in vitro
and promote a reparative effect on rabbit degenerated intervertebral disks.[22]
[23] Intra-articular knee injection of PRP results in pain relief and improves knee function
and quality of life in younger patients with a low degree of articular degeneration.[24] Previous studies demonstrated that PRP by periarticular injection, sacroiliac joint
injection, or intradiskal injection results in significant improvement in pain scores
for low back pain.[25]
[26]
In contrast to this promising finding, however, some relevant randomized controlled
trials (RCTs) showed that PRP injection had no influence on pain scores and patient
satisfaction for low back pain.[27]
[28] Considering these inconsistent effects, we therefore conducted a systematic review
and meta-analysis of RCTs to evaluate the effectiveness of PRP injection in patients
with low back pain.
Materials and Methods
This systematic review and meta-analysis were conducted according to the guidance
of the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement[29] and the Cochrane Handbook for Systematic Reviews of Interventions.[30] All analyses were based on previous published studies. Thus no ethical approval
and patient consent were required.
Literature Search and Selection Criteria
PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library were systematically
searched from inception to September 2017, with the following keywords: platelet-rich plasma or PRP, and low back
pain or lumbar
pain. To include additional eligible studies, the reference lists of retrieved studies
and relevant reviews were also hand-searched, and the process was performed repeatedly
until no further article was identified. Conference abstracts meeting the inclusion
criteria were also included.
The inclusion criteria were as follows: study population, patients with low back pain;
intervention, platelet-rich plasma; control intervention; outcome measure, pain scores;
and study design, RCT.
Data Extraction and Outcome Measures
The following information was extracted for the included RCTs: first author, publication
year, sample size, baseline characteristics of patients, PRP, control, study design,
pain scores within 8 weeks, > 50% pain relief at 3 months, relatively good patient
satisfaction, and adverse events. The author was contacted to acquire the data when
necessary.
The primary outcome was pain scores within 8 weeks. Secondary outcomes included > 50%
pain relief at 3 months, relatively good patient satisfaction, and adverse events.
Quality Assessment in Individual Studies
The Jadad scale was used to evaluate the methodological quality of each RCT included
in this meta-analysis.[31] This scale consisted of three evaluation elements: randomization (0–2 points), blinding
(0–2 points), and dropouts and withdrawals (0–1 points). One point would be allocated
to each element if they were mentioned in the article, and another 1 point would be
given if the methods of randomization and/or blinding were detailed and described
appropriately. If methods of randomization and/or blinding were inappropriate, or
dropouts and withdrawals had not been recorded, 1 point was deducted. The score of
the Jadad scale varies from 0 to 5 points. An article with a Jadad score ≤ 2 was considered
of low quality. If the Jadad score was ≥ 3, the study was deemed high quality.[32]
Statistical Analysis
Mean differences (MDs) with 95% confidence intervals (CIs) for continuous outcomes
(pain scores within 8 weeks) and risk ratios (RRs) with 95% CIs for dichotomous outcomes
(> 50% pain relief at 3 months, relatively good patient satisfaction, and adverse
events) were used to estimate the pooled effects. An I2 value > 50% indicates significant heterogeneity. The random-effects model with DerSimonian
and Laird weights was used in all analyses. Sensitivity analysis was performed to
detect the influence of a single study on the overall estimate via omitting one study
in turn when necessary. Owing to the limited number (< 10) of included studies, publication
bias was not assessed. A p < 0.05 in two-tailed tests was considered statistically significant. All statistical
analyses were performed with Review Manager v.5.3 (The Cochrane Collaboration, Software
Update, Oxford, United Kingdom).
Results
Literature Search, Study Characteristics, and Quality Assessment
The flowchart for the selection process and detailed identification is presented in
[Fig. 1]. A total of 372 publications were identified through the initial search of databases.
Ultimately, three RCTs were included in the meta-analysis.[25]
[27]
[28]
Fig. 1 Flow diagram of study searching and selection process. RCT, randomized controlled
trial.
[Table 1] summarizes the baseline characteristics of the three eligible RCTs in the meta-analysis.
The three studies were published between 2016 and 2017, and sample sizes ranged from
40 to 46 with a total of 131. The PRP group and control group had similar characteristics
at baseline. Two RCTs reported an intra-articular injection with PRP versus a steroid
injection,[25]
[28] and one RCT reported intradiskal PRP versus a contrast agent.[27]
Table 1
Characteristics of included studies
|
No.
|
Study
|
PRP group
|
Control group
|
|
Jada scores
|
|
N
|
Age, y
|
Male, n
|
BMI, kg/m2
|
Methods
|
N
|
Age, y
|
Male, n
|
BMI, kg/m2
|
Methods
|
Type
|
|
|
1
|
Wu et al[28]
|
23
|
52.91 ± 7.60
|
10
|
22.56 ± 1.39
|
Intra-articular injection with PRP
|
23
|
52.78 ± 7.25
|
9
|
22.38 ± 1.45
|
Intra-articular injection with local anesthetic/corticosteroid
|
Lumbar facet joint syndrome
|
5
|
|
2
|
Singla et al[25]
|
20
|
35.20 ± 12.86
|
16
|
23.69 ± 2.54
|
Ultrasound-guided sacroiliac joint injection with 3 mL leukocyte-free PRP with 0.5 mL
calcium chloride
|
20
|
37.00 ± 10.89
|
16
|
22.41 ± 2.08
|
Ultrasound-guided sacroiliac joint injection with 1.5 mL methylprednisolone (40 mg/mL)
|
Sacroiliac joint pain
|
3
|
|
3
|
Tuakli-Wosornu et al[27]
|
29
|
41.4 ± 8.08
|
15
|
–
|
Intradiskal PRP
|
16
|
43.80 ± 8.91
|
9
|
–
|
Intradiskal contrast agent
|
Symptomatic degenerative intervertebral disk
|
4
|
Abbreviations: BMI, body mass index; PRP, platelet-rich plasma.
Among the three RCTs, two studies reported the pain scores within 8 weeks,[25]
[27] two studies reported > 50% pain relief at 3 months,[25]
[28] two studies reported relatively good patient satisfaction,[27]
[28] and three studies reported adverse events.[25]
[27]
[28] Jadad scores of the three included studies varied from 3 to 5; all three studies
were considered high quality according to our assessment.
Primary Outcome: Pain Scores within 8 Weeks
These outcome data were analyzed with a random-effects model. The pooled estimate
of the two included RCTs suggested that compared with the control group for low back
pain, PRP injection was associated with significantly decreased pain scores (MD: − 1.47;
95% CI, − 2.12 to − 0.81; p < 0.0001), with no heterogeneity among the studies (I2: 0%; heterogeneity p = 0.84) ([Fig. 2]).
Fig. 2 Forest plot for the meta-analysis of pain scores within 8 weeks. PRP, platelet-rich
plasma.
Sensitivity Analysis
No heterogeneity was observed among the included studies for the pain scores. Thus
we did not perform a sensitivity analysis by omitting one study in turn to detect
the source of heterogeneity.
Secondary Outcomes
Compared with control intervention for low back pain, PRP injection could substantially
improve the number of patients with > 50% pain relief at 3 months (RR: 4.14; 95% CI,
2.22–7.74; p < 0.00001; [Fig. 3]) and offer relatively good patient satisfaction (RR: 1.91; 95% CI, 1.04–3.53; p = 0.04; [Fig. 4]) with no increase in adverse events (RR: 1.92; 95% CI, 0.94–3.91; p = 0.07; [Fig. 5]).
Fig. 3 Forest plot for the meta-analysis of pain relief at 3 months. PRP, platelet-rich
plasma.
Fig. 4 Forest plot for the meta-analysis of relatively good patient satisfaction. PRP, platelet-rich
plasma.
Fig. 5 Forest plot for the meta-analysis of adverse events. PRP, platelet-rich plasma.
Discussion
PRP is an autologous blood derivative containing high concentrations of activated
growth factors and cytokines (e.g., platelet-derived growth factor, transforming growth
factor, fibroblast growth factor, insulinlike growth factor 1, and epidermal growth
factor).[33]
[34]
[35]
[36] These elements serve as important humoral mediators to induce an anti-inflammatory
effect and natural healing cascade by promoting cell proliferation, migration and
differentiation, protein transcription, extracellular matrix regeneration, angiogenesis,
and collagen synthesis.[37]
[38]
[39]
Our meta-analysis concluded that PRP injection resulted in significantly improved
pain relief (as evidenced by the meta-analysis of pain scores within 8 weeks and > 50%
pain relief at 3 months) and patient satisfaction for patients with low back pain.
In addition, one included RCT revealed that PRP injection was able to result in sustained
and more reduction in pain visual analog scores and lumbar functional improvements
at the end of 6 months than local anesthetic using a corticosteroid. These results
indicated autologous PRP served as the superior treatment option for longer duration
efficacy for low back pain compared with corticosteroids. Patients with osteoarthritis
of the hip, knee, and ankle experienced significantly favorable pain relief and functional
improvement after intra-articular PRP injection.[40]
[41]
[42] A previous study demonstrated PRP injection produced better clinical outcomes than
hyaluronic acid injection at 3 to 12 months posttreatment for knee osteoarthritis.[40]
The complications of PRP injection mainly included complications related to puncture
and complications related to various drugs, but they all are exceedingly rare. The
adverse events for PRP injection involved postinjection pain and stiffness, chest
pain, and difficulty breathing, giddiness, and contralateral pain.[28] Our meta-analysis demonstrated no increase in adverse events after PRP injection
compared with control group. All included RCTs reported no serious adverse events.
Several limitations should be considered. First, our analysis was based on only three
RCTs, and all of them had a relatively small sample size (n < 100). Overestimation of the treatment effect was more likely in smaller trials
compared with larger samples. The causes of low back pain in the included studies
were different, and it may have had an influence on the pooling results. Next, the
follow-up time of PRP varied from 3 months to 1 year, and longer durations were needed
to confirm this issue. Finally, some unpublished and missing data might have lend
bias to the pooled effect.
Conclusion
PRP injection showed an important ability to provide pain relief and patient satisfaction
for those with low back pain. PRP injection is recommended to be administrated for
low back pain with caution.
