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Authors; Qiukui Hao, and Melissa Walter.
Lower back pain (LBP) is a syndrome rather than a disease. LBP is characterized as pain in the region at the back of the body from the lower edge of the twelfth rib to the lower gluteal folds, with or without pain extending to 1 or both legs that persists for at least 1 day.1 Chronic LBP refers to pain that persists for more than 12 weeks, even after receiving treatment for its potential causes.2 LBP is a common and complex musculoskeletal problem and is the leading cause of disability or absence from work globally.1,3,4 People in all age groups, from children to older adults, can be affected by LBP. Approximately 60% to 80% of people experience LBP at some point during their lifetime.5 The point prevalence of activity-limiting LBP was about 7.3%, responsible for 60.1 million disability-adjusted life-years in 2015.4
The prevalence of LBP increases with age and peaks around 80 to 89 years.3 The age-adjusted prevalence of LBP was higher in females than males.3 Due to population increase and aging, LBP-induced years lived with disability, related costs, and health care use have increased substantially and will continue to increase in coming decades.4 Although most LBP episodes will recover within 4 to 6 weeks with little or no serious consequence,4,6,7 around 30% of people will suffer from at least 1 recurrent episode within 1 year after recovery.4 Similar epidemiology data and clinical features for LBP were reported in a Canadian national population health survey.6 In Canada, about 3% of people visited the emergency department with back pain from 2009 to 2015 in the largest emergency department in Atlantic Canada; among those with back pain, over 60% of patients were diagnosed with LBP.8
Only a small proportion of people with LBP had exact causes, such as vertebral fracture, infections, inflammatory disorders, or malignant disease.4 These types of disease-specific LBP need specific medical attention and management targeting the cause. However, most people with LBP cannot find the specific source of the pain. Multiple factors, including issues with intervertebral discs, facet joints, or vertebral end plates can cause nonspecific LBP.4 Lifestyle factors like smoking, obesity, and low levels of physical activity may also contribute to this type of pain, as well as psychological factors and pain-processing mechanisms.4 Identifying the risk factors of LBP is important for treatment.
There are numerous treatment options available for LBP, including pharmacological and non-pharmacological therapies.9 Current guidelines suggest physical (mainly exercise), psychological interventions, and self-management strategies such as education, advice to remain active, or applying superficial heat, while these guidelines do not strongly emphasize surgery or injections.7,10 The effectiveness, safety, and cost-effectiveness are crucial considerations for choosing emerging interventions. Despite the emergence of injectable interventions for patients with LBP, they have not been widely implemented in clinical practice due to inconsistent or low-quality evidence regarding their clinical effectiveness and safety, and were not recommended by guidelines.7,10,11
Platelet-rich plasma (PRP) is an injectable biologic product, which consists of a higher concentration of the patient’s platelets in a small amount of plasma than in peripheral blood.12 Clinicians have used PRP to treat various conditions for over 30 years,12 including musculoskeletal disorders,13 surgical wounds,14 thin endometrium,15 premature ovarian failure,16 and acne scars.17 PRP contains numerous growth factors in platelet granularities such as fibroblast growth factor, transforming growth factors beta-1, angiogenesis factor, and growth factor.12 The exact mechanisms by which PRP and its components can treat these diseases are not yet clear, but they might be involved in tissue repair, pain relief, and regenerative processes.13-17
PRPIs are becoming 1 potential intervention for patients with LBP.18 Based on a nonsystematic literature review,19 several observational studies have reported the effectiveness of PRPIs; however, there is lack of high-quality clinical trials in this population. Given the uncertain and developing evidence base for PRPIs, the objective of this report is to evaluate the recent evidence on the clinical effectiveness and safety of PRPIs for the treatment of LBP in adults.
What is the clinical effectiveness of platelet-rich plasma injections for the treatment of lower back pain in adults?
An information specialist conducted a literature search on key resources, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the International HTA Database, the websites of Canadian and major international health technology agencies, and a focused internet search. The search approach was customized to retrieve a limited set of results, balancing comprehensiveness with relevancy. The search strategy comprised controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. Search concepts were developed based on the elements of the research questions and selection criteria. The main search concepts were platelet-rich plasma injections and back pain. Conference abstracts were excluded. Retrieval was limited to the human population. The search was completed on April 27, 2023 and limited to English-language documents published since January 1, 2018.
One reviewer screened citations and selected studies. In the first screening level, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1. For this report, we considered a review to be a systematic review if it indicated that the evidence was searched for systematically and had clear inclusion and exclusion criteria.
Selection Criteria.
Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published before 2018. Systematic reviews and health technology assessments in which all relevant primary studies were captured in at least 1 other more recent or more comprehensive systematic review were excluded.
The included systematic reviews were critically appraised by 1 reviewer using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2).20 Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
A total of 123 citations were identified in the literature search. Following screening of titles and abstracts, 90 citations were excluded and 33 potentially relevant reports from the electronic search were retrieved for full-text review. Ten potentially relevant publications were retrieved from the grey literature search for full-text review. Of these potentially relevant articles, 39 publications were excluded for various reasons, and 4 systematic reviews met the inclusion criteria and were included in this report. Appendix 1 presents the PRISMA21 flow chart of the study selection.
Additional references of potential interest are provided in Appendix 6.
We included 4 systematic reviews in this report.22-25 Two23,25 of the 4 systematic reviews had broader inclusion criteria on interventions than the present report. Specifically, both systematic reviews23,25 included both PRPIs and mesenchymal stem cell interventions. Only the subset of studies reporting on PRPIs was relevant to this rapid review and are described in the remainder of our report. Additional details regarding the characteristics of included publications are provided in Appendix 2.
Appendix 5 includes a table describing the overlap in relevant primary studies in the included systematic reviews.
Two22,25 of 4 systematic reviews included single-arm meta-analyses comparing the outcome after treatment to baseline, 1 systematic review24 included the meta-analyses comparing PRPIs to control interventions, and 1 systematic review23 summarized the findings from primary studies narratively and did not conduct a meta-analysis. The number of primary studies involving PRPIs that were included in the systematic reviews ranged from 3 to 15 primary studies,22,25 which comprised randomized controlled trials (RCTs), observational studies, and case reports. One systematic review25 was published in 2018, 1 systematic review24 was published in 2020, 1 systematic review23 was published in 2022 and 1 systematic review22 was published in 2023 with the search up to April 18, 2022. We found 1 systematic review24 that consisted of 3 RCTs, which were also included in another systematic review.25 We utilized both systematic reviews24,25 because the former compared PRPI interventions to control interventions in their meta-analyses,24 while the latter had a wider range of studies but only conducted single-arm meta-analyses.25
Of the 4 systematic reviews, 2 systematic reviews22,24 were from China, 1 systematic review was from Italy,23 and 1 systematic review was from the US.25 One systematic review22 presented the countries or regions of included primary studies. Of the 6 studies within this systematic review, 3 RCTs were conducted in the US and 3 observational studies were conducted in Japan, India, and the US.22
Two22,23 of 4 systematic reviews22-25 involved patients with chronic discogenic LBP. One review included patients with LBP but did not report the type or duration of LBP.24 One review included patients with LBP and lower extremity pain (duration not reported).25 The number of included patients in 3 systematic reviews22-24 ranged from 127 to 198. The mean age of patients in primary studies within 2 systematic reviews22,24 ranged from 33 years to 52.91 years and age was not reported in the 2 remaining systematic reviews.23,25 In 2 systematic reviews, the percentage of males ranged from 39% to 80%22,24 and was not reported in the other 2 systematic reviews.23,25
One systematic review24 compared the effectiveness and safety of PRPIs to control injections without PRPIs, which included anesthetic, steroids, or contrast agents. The remaining 3 systematic reviews22,23,25 reported the before and after changes for receiving PRPIs without a comparator group. PRPI sites or routes of administration were reported as intradiscal,22,25 sacroiliac joint,24,25 intra-articular,24,25 and epidural injection.25 One systematic review23 did not report the site of the injection for PRP, but reported the injected PRP volumes ranged from 1 mL to 3 mL, when reported.23,24 None of the systematic reviews22-25 clearly reported the types of PRP used (pure or leucocyte PRP), the frequencies of the injections, treatment history, and the co-interventions for LBP.
All 4 systematic reviews reported or discussed pain outcomes.22-25 Pain was assessed by the visual analogue scale (VAS) or numerical rating scale (NRS). In 2 systematic reviews,22,24 the VAS or NRS were reported in a 10-point scale, while the scale of pain measures was clear in the other 2 systematic reviews.23,25 The disability was assessed in 2 systematic reviews22,25 by Oswestry Disability Index (ODI),22 Functional Rating Index, or Roland-Morris Disability Questionnaire.25 The pain or disability scales used in individual studies were not reported in detail, including their psychometric properties and interpretation scores such as what direction represents improvement or worsening, or minimal important difference. Three systematic reviews22-24 mentioned adverse events or major complications. One systematic review23 described the MRI changes after PRPIs treatment. One systematic review24 also reported the rate of patient satisfaction. Three systematic reviews reported the mean or median duration of follow-up,22-24 which ranged from 1 week to 60 weeks. The remaining systematic review did not report the duration of follow-up.25
In all 4 systematic reviews,22-25 the objective was clearly described, multiple databases were searched, keywords or medical subject terms or keywords of the search and study selection flow charts were provided, the review authors declared no conflicts of interest, lists of included articles were presented and the study characteristics were described. None of the systematic reviews provided lists of excluded articles or assessed the sources of funding in individual studies. Despite searching in multiple databases, 3 systematic reviews22-24 did not report performing a grey literature search and 2 systematic reviews23,25 did not report searching the Embase database specifically. These limitations may result in missing some studies (unpublished or studies conducted in Europe) or mis-identification of potential publication bias.
At least 2 reviewers independently performed the article selection and data extraction in 1 systematic review.23 Two reviewers independently selected articles in 2 systematic reviews,22,25 but it was unclear how the data extraction was performed. In the fourth systematic review,24 it was unclear how article selection and data extraction were conducted. The possibility of inappropriate inclusion or exclusion or errors in data extraction cannot be ruled out. Although 3 systematic reviews22-24 assessed the risk of bias of included individual studies and reported study quality, they did not assess the potential impact of study risk of bias on the interpretation of results. One systematic review23 authors judged that only 1 out of 7 primary studies had high-quality (low risk of bias);in another systematic review22, some meta-analyses only included 1 or 2 primary observational studies; therefore, the results of these analyses may be driven by individual studies with high risk of bias. One systematic review25 evaluated the grading of evidence, considering the quality of included individual studies and stratified the assessment according to PRPI sites. However, the review25 did not include an outcome-specific assessment of evidence, making it challenging to interpret the reported level of evidence. In 2 systematic reviews22,25 with substantial statistical heterogeneity, no analysis was conducted to explore the observed heterogeneity.
The systematic review by Peng et al. (2023)22 included a single-arm meta-analysis to compare the changes in pain and disability outcomes between post-PRPI treatment and baseline and calculated incidence rates for improvement; this analysis was methodologically flawed. The review authors22 calculated the incidence rate for improvement in outcome measures of over 30% or 50% based on the pooled odds ratio (OR) in their meta-analysis. The formula used to calculate the incidence rate was “incidence rate= OR/(1+OR)” and the results were reported as percentages. To accurately calculate the incidence rate, 1 must consider the new events, the population at risk, and a time frame, and report it as events per people-year. Reporting the incidence rate results based on a pooled OR is unreliable. Alternatively, the systematic review authors could have extracted the proportion of patients who experienced a 30% or 50% decrease in pain or disability and use appropriate proportional meta-analysis to get a pooled proportion.26
Additional details regarding the strengths and limitations of included publications are provided in Appendix 3.
One included systematic review24 compared PRPIs and controls interventions without PRPIs. Two systematic reviews22,25 included data from RCTs or observational studies on patients who received PRPI and conducted meta-analyses of data from the intervention arm alone. The fourth systematic review23 provided narrative summaries of the findings of the individual studies that were included (1 out of 7 included individual studies had a control group and the details of control were unclear). Appendix 4 presents the main study findings. Due to some overlap in the studies included in the 2 systematic reviews with single-arm meta-analyses22,25 the pooled estimates from the 2 systematic reviews may contain some of the same individual study data (Appendix 5).
All included systematic reviews22-25 reported pain scores after PRPI in people with LBP, and generally demonstrated statistically significant reductions from baseline or compared to a control. One systematic review24 reported that PRPI was statistically significantly more effective than the control group in reducing pain scores within 8 weeks. However, the method of measurement for the pain scores was unclear. Two systematic reviews22,25 reported the pooled estimates of post-PRPI pain scores at various time points from single-arm meta-analysis. These systematic reviews reported that pain scores were statistically reduced at 1 month,22 2 months,22 6 months,22,25 and 12 months25 after PRPI compared with before PRPI with substantial statistical heterogeneity (I2 = 77% to 98%). However, the comparisons of pain scores between post-PRPI time points were not statistically significant.22 For PRP administered by lumbar facet joint injection, intra-articular injection and sacroiliac joint injection, the systematic review by Sanapati et al. (2018)25 provided a narrative summary of findings for each study in tables, indicating that most studies reported positive effects of PRPI on pain (i.e., pain decreased). One systematic review23 reported the findings from 4 primary studies in which pain scores were numerically lower after PRPI treatment (unclear time point) compared with before PRPI treatment. However, it is unclear what methods were used to measure pain scores and the time frame for outcome measures.
The systematic review by Sanapati et al. (2018)25 also reported the level of evidence, but failed to specify it based on the outcomes (pain or disability). PRP treatment administered through lumbar disc injection has a level III (fair) evidence in reducing pain.25 However, for lumbar facet joint, intra-articular injection, and sacroiliac joint injection, the level of evidence was level IV (limited).25 In this review,25 level III (fair) evidence was defined as “evidence obtained from at least one relevant high quality nonrandomized trial or observational study with multiple moderate or low-quality observational studies” and level IV (limited) was defined as “evidence obtained from multiple moderate or low-quality relevant observational studies” (page 519, Table 1).
One systematic review24 reported that PRPI was statistically significantly more effective than the control group in improving the rate of patients who experienced at least 50% pain relief at 3 months. Another systematic review22 reported the calculated incidence rates based on pooled odds ratios for patients who experienced more than 30% and 50% pain relief after PRPI treatment compared with before PRPI treatment at 1 month, 2 months, and 6 months, with more than half of patients reaching at least 30% of pain relief at any measured time points. However, the reliability of these incidence rates is questioned due to the use of flawed methods or formulas.
Two systematic reviews22,25 reported disability outcomes. One systematic review22 evaluated the incidence rates of patients who experienced a 30% or 50% decrease from baseline in disability score after PRPI treatment. This review reported 40.2% of patients reaching at least a 30% decrease in disability score at 2 months, and 53.9% reaching at least a 50% decrease in disability score at 6 months. However, we had concerns regarding the accuracy of the findings due to the utilization of incorrect methods or formulas in this review. The second review25 reported that the disability scores were numerically lower after PRPI treatment at 3 months or 6 months than before PRPI treatment.
One systematic review reported that PRPI can statistically significantly enhance patient satisfaction rates compared to control interventions.24 The details of the outcome measure, such as the time it was taken, the tool used to assess patient satisfaction and its psychometric properties, and whether the outcome assessors were blinded to group allocation, were not provided.
All 4 systematic reviews22-25 considered adverse events, and 1 review24 provided a meta-analysis on adverse events. Based on the meta-analysis,24 there was no statistical difference in adverse events between patients in the PRPI treatment group and the control group. Two systematic reviews reported that no serious adverse events or complications occurred.22,23 In the fourth systematic review,25 adverse events were considered for some individual studies in tables, and PRPIs did not appear to have serious safety concerns. However, the definitions of considered adverse events were not provided.
One systematic review based on 2 individual studies noted that, for most patients, there were no significant changes in hydration level, height of the intervertebral disc, and disc bulging in MRI after PRPI intervention compared to before PRPI intervention.23
There are some methodological limitations in the body of evidence presented. In this report, we identified 4 systematic reviews22-25 to answer the research question on clinical effectiveness of PRPIs. Two22,25 of these reviews used single-arm meta-analysis to provide before-after comparisons of outcomes in within the PRPI group, while 1 systematic review23 narratively summarized the findings of the included primary studies. Only 1 systematic review24 included a meta-analysis comparing PRPI to the control group. Most of the primary studies included in these reviews were observational studies, with only a small number of RCTs (3 RCTs per systematic review in 2 systematic reviews22,24). The sample sizes of included systematic reviews22-24 were relatively small, with fewer than 200 patients. For the results from before-after comparison, observational studies or RCTs with high risk of bias, we cannot conclusively determine that the changes in the outcome measure are solely caused by the PRPI intervention, and there may be potential selection bias, recall bias, or performance bias. None of the systematic reviews conducted subgroup analysis or meta-regression to investigate the observed statistical heterogeneity. Moreover, 1 systematic review22 employed flawed methods to calculate the incidence rate.
The body of evidence also has issues with unclear reporting. All included systematic reviews22-25 did not provide a comprehensive description of the types of PRPI used such as pure or leucocyte PRP or the frequencies of the injections. In addition, the treatment history or co-interventions with the PRPIs intervention were not clearly provided. We are unclear about the psychometric properties for disability measures, the definition of the patient satisfaction and adverse events. Thus, the interpretations of evidence regarding these outcomes were limited.
We also noted some evidence gaps in this report. There was no systematic review conducted that considered the patients' perspective by comparing the observed mean difference with the tool’s minimal important difference in their statistical findings. Moreover, no systematic review was found that reported the comparisons between PRPI and other conservative treatments such as non-steroidal anti-inflammatory drugs, exercise or physiotherapy in the current report. The primary studies of 1 included systematic review22 were conducted in Asia and the US. Thus, the generalizability of these findings to settings in Canada is uncertain.
Four systematic reviews22-25 were identified to address the clinical effectiveness of PRPI for patients with LBP. These studies provided evidence from RCTs, before and after studies, and case reports to suggest that patients with LBP treated with PRPI had statistically significantly reduced pain (up to 12 months) or disability scores (up to 6 months) compared to before PRPI treatment. One systematic review24 that included 3 RCTs reported that PRPI may be better than control injections (including steroid injections) for patients with LBP in reducing pain scores within 8 weeks, improving the number of patients who experienced at least 50% pain relief at 3 months, and enhancing patient satisfaction, without increasing the adverse event rate. No major complications or adverse effects related to PRPIs were reported in all included systematic reviews.22-25 Due to the potential bias of observational studies and before-after designs, these findings need to be interpreted with caution.
Individuals with LBP typically require a range of interventions, both pharmacological and non-pharmacological interventions.9 One systematic review23 only included patients who did not respond to conservative treatment and had MRI evidence of disc degeneration. Other included systematic reviews22,24,25 did not clearly report the indication for starting PRPI treatment. Additionally, the definition of conservative treatment was unclear, leaving uncertainty about whether all individuals need an MRI or conservative treatment before further intervention with PRPI.
The prognosis of patients with LBP is relatively good in that most patients can recover with other treatment such as exercise or physiotherapy;4,6,7,9 however, we did not identify any studies comparing PRPI with exercise or physiotherapy that met our inclusion criteria. We may need such comparative studies to fully assess the benefits of adding PRPI to usual care or other interventions. When there is acceptable variability in population and intervention characteristics, conducting a systematic review with network meta-analysis may be helpful to get the relative effect of PRPI versus other active interventions. Considering the current limitations of the body of evidence, primary studies with robust design and adequate sample size that address the relative effects of PRPI versus other treatments are also needed. The accessibility and cost of PRPI, and the values or preferences of patients regarding injections can also play a significant role in the decision-making process.
confidence interval
lower back pain
numerical rating scale
Oswestry Disability Index
odds ratio
platelet-rich plasma
platelet-rich plasma injections
randomized controlled trials
risk ratio
standardized mean difference
visual analogue scale
Contributor: Elizabeth Carson
Selection of Included Studies.
Note that this appendix has not been copy-edited.
Characteristics of Included Systematic Reviews.
Note that this appendix has not been copy-edited.
Strengths and Limitations of Systematic Reviews Using AMSTAR 220.
Note that this appendix has not been copy-edited.
Summary of Findings by Outcome — Pain.
Summary of Findings by Outcome — Disability.
Summary of Findings by Outcome — Patient Satisfaction.
Summary of Findings by Outcome — Adverse Events.
Note that this appendix has not been copy-edited.
Overlap in Relevant Primary Studies Between Included Systematic Reviews.
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