|Year : 2018 | Volume
| Issue : 3 | Page : 1088-1093
Clinical evaluation of intra-articular platelet-rich plasma injection for the treatment of knee osteoarthritis
Taher A Eid, Osama G Ahmed, Mohamed Y Abuzeid
Department of Orthopedics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||13-Apr-2017|
|Date of Acceptance||21-May-2017|
|Date of Web Publication||31-Dec-2018|
Mohamed Y Abuzeid
Shibein El-Kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate results of intra-articular injection of plasma sample rich in platelets for the treatment of knee osteoarthritis (OA).
OA is a progressive, chronic condition leading to pain and loss of function that reduce patients' quality of life.
Materials and methods
The study was performed on 30 knees of 30 patients with age 30–65 years. All of the patients presented with knee OA grade I, II, and III and were treated with two intra-articular platelet-rich plasma (PRP) injections with three weeks interval. Preparation was done by centrifugation of 50 ml blood in two separate cycles, finally resulting in 5 ml of PRP then get activated by calcium chloride (CaCl2) at concentration of 50 μl/1 ml PRP, added just before injection. Western Ontario and McMaster universities score was used for clinical evaluation. Complications and adverse events were also recorded.
Mean age of patients was 52 years. All of them were followed up to 12 months. The clinical results were classified on subjective base and were graded as excellent in 19 (63.3%) patients, good in six (20%) patients, and poor in five (16.7%) patients. No complications were noted. There was significant significance between BMI and clinical success (P = 0.000). The study showed significant association between grade of OA and clinical success (P = 0.008).
Maximal improvement occurred in a month and continued above basal levels in 12 months follow-up, especially in the young individuals. These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy.
Keywords: intra-articular injection, osteoarthritis, platelet-rich plasma
|How to cite this article:|
Eid TA, Ahmed OG, Abuzeid MY. Clinical evaluation of intra-articular platelet-rich plasma injection for the treatment of knee osteoarthritis. Menoufia Med J 2018;31:1088-93
|How to cite this URL:|
Eid TA, Ahmed OG, Abuzeid MY. Clinical evaluation of intra-articular platelet-rich plasma injection for the treatment of knee osteoarthritis. Menoufia Med J [serial online] 2018 [cited 2019 Mar 20];31:1088-93. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/1088/248736
| Introduction|| |
Osteoarthritis (OA) is a progressive, chronic condition leading to pain and loss of function that reduce patients' quality of life. It has a multifactorial etiology and occurs as a result of various biochemical, biomechanical, inflammatory, and immunological factors).
The diagnosis of OA is primarily a clinical one based on history of joint pain worsened by movement, weight bearing, and physical examination findings. Plain radiography may help in the diagnosis, even if the degree of pain does not correlate with the severity of radiographic disease, especially in the early stages.
Currently, the Kellgren–Lawrence (KL) grading scheme is the most widely used and accepted standard for diagnosis of radiographic OA. A KL grade of 0 indicates that no radiographic features of OA are present, whereas a KL grade of 1 is defined as doubtful JSN (joint space narrowing) and possible osteophytes lipping. Radiographic OA receives a KL grade of 2, denoting the presence of definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph. Further disease progression is graded as KL 3, characterized by multiple osteophytes, definite JSN, sclerosis, and possible bony deformity. KL grade 4 is defined by large osteophytes, marked JSN, severe sclerosis, and definitely bony deformity.
The goal of OA treatment is to control symptoms and to prevent disease progression by a combination of nonpharmacological and pharmacological modalities. Pharmacological treatment options include analgesics, NSAIDs, glucosamine sulphate plus chondroitin sulphate, and the intra-articular injection of steroids or hyaluronan. Finally, surgical interventions should be reserved as a last-line management strategy for OA.
New information regarding OA pathophysiology indicates that imbalance between anabolic and catabolic mechanisms, growth factors (GFs), and inflammatory mediators play an important role. The current research trend is towards preventive interventions, including platelet-rich plasma (PRP) and autologous conditioned serum, which through the release of GFs, regulation of anti-inflammatory signals, and modulation of angiogenesis may contribute to the prevention of joint degenerative progression and enhance the repair process,.
PRP therapy is a simple, low cost, and minimally invasive method that allows a natural concentrate of autologous GFs to be obtained from the blood. This therapy is widely experimented in different fields of medicine to test its potential to enhance tissue regeneration.
The aim of this study was to evaluate results of intra-articular injection of PRP for the treatment of knee OA.
| Materials and Methods|| |
The study was performed on 30 knees of 30 patients with age 30–65 years. All of the patients presented with knee OA were treated with two intra-articular PRP injections with three weeks interval. All of them were done in orthopedic outpatient clinic under complete sterile condition, and were followed up for 12 months.
The study was approved by Ethical Committee of Menoufia Faculty of Medicine. An informed consent was taken from each patient.
- Primary knee OA with history of chronic pain with or without swelling with imaging study of grade I, II, or III with degenerative knee changes
- Patients who did not improve with medical treatment and physiotherapy.
- Patients with secondary OA
- Patients with other diseases of the knee
- Grade IV knee OA
- History of steroid injection during the last 3 month
- Thrombocytopenic patients.
Platelet-rich plasma preparation
- 50 cm blood collected in 10 plain sterile tubes each containing 750 μg anticoagulant citrate dextrose
- The blood samples were centrifuged at 200 g (1500 rpm) for 15 min
- The plasma was separated in other sterile tubes then was centrifuged at 1200 g (9000 rpm) for 10 min
- The supernatant was discarded from each tube and the platelet remained in the bottom half cm of plasma in each tube
- Finally, 5 ml PRP was collected from initial 50 cm blood collected
- A 250 μg of CaCl2 at concentration 50 μl for each 1 ml PRP was added just before injection.
Injection technique and follow-up
Patients were told to:
- Avoid corticosteroid medications for 2 − 3 weeks prior to the procedure
- Stop taking NSAIDs, such as aspirin or ibuprofen; or arthritis medications such as celebrex, a week prior to the procedure
- Do not take anticoagulation medication for 5 days before the procedure
- Drink plenty of fluids the day before the procedure
- Some patients may require antianxiety medication immediately before the procedure.
Although the American Academy of Orthopedic Surgeons published these preinjection guidelines, the organization does not advocate for or against PRP treatment for OA.
The skin was sterilized, and the infiltration was performed using a classic lateral approach with a 22 G needle. At the end of the procedure, the patient was asked to bend and extend the knee a few times to allow the PRP to spread throughout the joint before becoming a gel.
After the platelet-rich plasma injection
The PRP typically stimulates a series of biological responses, and the injection site may be swollen and painful for about 3 days.
Patients are advised to use ice bags at site of injection for a few days and avoid putting strain on the affected joint.
Doctors may require or suggest that a patient
- Use crutches to decrease the load on the affected joint
- Decrease the body weight
- Do regular exercise.
Patients who do not have physically demanding jobs can usually go back to work the next day. Patients can resume normal activities when swelling and pain decrease, typically a few days after the injections. Patients should not begin taking anti-inflammatory medications until approved by the doctor.
Patients were prospectively evaluated before and at the end of the treatment (2 months after the first injection), and at follow-ups 1, 3, and 12 months after the treatment. Western Ontario and McMaster universities (WOMAC) score was used for clinical evaluation. The WOMAC measures five items for pain (score range 0–20), two for stiffness (score range 0–8), and 17 for functional limitation (score range 0–68). Complications, adverse events, and patient satisfaction were also recorded.
The data collected were tabulated and analyzed by SPSS (statistical package for the social sciences, released 2007, SPSS for windows, version 16.0; SPSS Inc., Chicago, Illinois, USA).
Two types of statistics were done.
The arithmetic mean is simply called the mean, it is the sum of all values divided by the number of these values. Examples of uses (analysis of BMI relation to results).
SD measures the degree of scatter of individual varieties around their mean.
Examples of uses (analysis of BMI relation to results).
- Wilcoxon signed rank test (nonparametric test): is a test of significance used for comparison between two related groups, not normally distributed, having quantitative variables. Examples of uses [analysis of WOMAC score in group 1 (excellent group)]
- Level of significance was set as P value less than 0.05. Examples of uses (BMI, grade of OA analysis in relation to results).
| Results|| |
Knee pain, stiffness, and functional limitation of the joint are evaluated by assessment of WOMAC score.
The study was performed on 30 patients (six male and 24 females) and all results were presented.
Their mean ± SD age was 52 ± 5 years (range: 30–65 years).
Among 30 patients, 19 patients had issues with right knees and 11 with left knees, two cases with grade I OA, 23 cases with grade II OA, and five cases with grade III OA.
The WOMAC subjective score improved markedly from the basal evaluation to the end of therapy [Table 1] and the follow-up study for a month was carried out. The mean basal WOMAC score was 21 ± 4 (range: 16–31) and after a month's follow-up the score was 42 ± 8 (range: 24–63.6).
|Table 1: The Western Ontario and McMaster universities score prior to injection in relation to results|
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After 3 months follow-up, the mean ± SD of WOMAC score was 47 ± 8 (range: 25–68.2). All cases continued follow-up till 12 months with mean score 45.5 ± 9 (range: 21–67). The values of WOMAC score in 12 months were above the basal values in all cases except for five cases that showed poor responses over the basal values [Table 2].
|Table 2: The Western Ontario and McMaster universities score in each group on first, third, and 12th month assessment|
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In the current study the BMI ranged from 22.2 to 54.11 kg/m2. There was significant significance between BMI and clinical success (P = 0.000). There were 100% success rate among patients whose BMI was less than 34.38 kg/m2 and 37.5% success rate among patient whose BMI greater than 34.38 kg/m2. The decreased efficacy of treatment was identified in patients with a higher BMI. The large body weight is an important risk factor in knee OA as it causes degeneration of the cartilage [Table 3].
The current study showed significant association between grade of OA and clinical success (P = 0.008), which proved that the more increase in grade of OA the less the improvement. This was explained by the older and more degenerative joints as it tend to have less viable cells, and with that a smaller potential for GF response.
No major adverse effects or complications related to injections were observed during the treatment and follow-up period, except for four cases that came with increased level of pain and swelling of injected knee for few days after injection. Pain and swelling were controlled by giving the patients acetaminophen and applying cold compresses.
In the current study no obvious changes were found in radiography after 3 months and 1 year from second injection, this is explained by the fact that PRP does not affect bone changes occurring during the degenerative process of OA as it is irreversible. Cartilage healing did not appear in radiography but appeared in computed tomography or MRI; and we depended on factors, such as the clinical improvement, pain control, and patient satisfaction.
Finally, the current study showed 83.3% success rate where 63.3% had excellent results (19 cases), 20% had good results (six cases), 16.6% had poor results (five cases), and 16.6% were lost from the study (five cases).
| Discussion|| |
PRP is derived from centrifuging the person's own whole blood, has a platelet concentration more than triple folds as that of whole blood and is the cellular component of plasma that settles after centrifugation. Its main advantages include its availability, affordability, and minimally invasive harvest, since it is produced from the patient's own blood after collection by simple venipuncture. PRP is safe with no serious complications and is currently used as a treatment for OA.
This study tries to spot light on application of PRP injection in primary knee OA showing its advantages and disadvantages. This study was conducted on 30 patients with primary OA grade I, II, and III. They were administered two injections of PRP and were followed up for 6 months. The follow-up is made by the Western Ontario and McMaster Universities Arthritis Index (WOMAC), which are standardized questionnaires used by health professionals to evaluate the condition of patients with OA of knee, including pain, stiffness, and physical function of the patients. It can be self-administered and was developed at Western Ontario and McMaster universities in 1982. The WOMAC measures five items for pain (score range 0–20), two for stiffness (score range 0–8), and 17 for functional limitation (score range 0–68).
In the current study the mean age of osteoarthritic patients was 52 years and ranged between 30 and 65 years old. This age was associated with higher incidence of knee OA, and these results were near to those reported by Albu et al., who reported the mean age of OA patients is 50 years old. Also these results were near to those reported by Seyed et al., who reported the mean of age to be 54 years old.
In current study, mean age who achieve excellent clinical success is 52.7, the mean age in good group is 55.6, and in case of poor group is 47, which prove no significant difference between age and clinical success (P = 0.357). Against these results were the results reported by Chiang et al., who reported that better results were achieved in younger patients. Filardo et al. reported that patients below 35 years had 65% statistical improvement, whereas patients above 55 years had 50% statistical improvement, and Ornetti et al. reported improvement mainly in younger patients. This difference in the results can be explained as young individuals were included in these studies.
In the current study there were 24 (80%) females and six (20%) males with ratio 4:1. This could be explained as women have multiple risk factors more than men to be exposed to OA as obesity, more elasticity of tendon of their lower body due to labor, knee joint is not straight as men, and also hormonal effect after menopause that makes women at higher risk for developing OA.
Twenty-one (87.5%) females statistically improved, four (66.7%) males statistically improved with no significant difference between males and females (P = 0.16). This agreed with Andrew et al., who reported no significant differences between men and women results, but this does not agree with the study of Cuervo et al., who compared the effect of the injection according to patient's sex. Male patients showed higher functional improvement. They explained that the better male outcome can be because of the different attitudes adopted by male and female patients toward the activities. The female patients were very cautious about activities despite their reduced pain and improved knee function, whereas male patients tended to test the level of improvement through more strenuous activities.
In the current study, the BMI ranged from 22.2 to 54.11 kg/m2, with an average of 36.15 kg/m2. There was significant significance between BMI and clinical success (P = 0.000). There were 100% success rate among patients whose BMI was less than 34.38 kg/m2 and 37.5% success rate among patient whose BMI greater than 34.38 kg/m2. This result is close to the results reported by Sampson et al. where the average BMI for participants was 25.0 kg/m2, with a range of 20.9 –32.5 kg/m2. The results matched with that of Filardo et al., who reported that the mean BMI was ranging from 18 to 32 kg/m2 with an average of 25 kg/m2. It agreed with José, who reported that the mean BMI was ranging from 22.2 to 35.6 kg/m2 with an average of 28.9 kg/m2. The study reported that decreased efficacy of treatment was identified in patients with a higher BMI. The large body weight is an important risk factor in knee OA as it causes degeneration of the cartilage.
The current study showed significant association between grade of OA and clinical success (P = 0.008), which proved that the more increase in grade of OA the less the improvement. This may be explained by the more degenerative cartilage, as it tends to have less viable cells with a smaller potential for GF response. This agreed with Chiang et al., who reported better results in patients with a low degree of cartilage degeneration and with Guerreiro et al., who reported the more degeneration of knee joint, the decreased potential for PRP injection therapy. Ornetti et al. reported that the improvement after PRP injection in patients was not affected by advanced degeneration.
The current study showed 83.3% success rate, where 63.3% had excellent results (19 cases), 20% had good results (six cases), and 16.6% had poor results (five cases).
There was a statistically significant improvement of all clinical scores obtained from the basal evaluation. This proved that PRP injection is an effective treatment in OA of the knee. Vannini et al. reported that the use of PRP leads to clinical improvements in the pain and dysfunction that result from knee OA at 12-month follow-up, this also agrees with Jang et al. who reported that application of PRP to treat OA of the knee can be considered a relatively new therapeutic option. Anitua et al.also reported that a series of intra-articular injections of PRP provide some short-term clinical benefit in symptomatic arthritis of the knee as demonstrated by improved clinical scores and decreased pain at 6-month follow-up. Similar finding was reported by José, who found PRP treatment showed positive effects in patients with knee OA and significant improvement by means of pain reduction, improved symptoms, and quality of life at 12-month follow-up. Macro et al. reported that patients were satisfied after PRP treatment and they maintained these positive results for at least 12 months without other medications or treatments, Fernandez-Moure et al. reported that PRP injection for knee OA is efficacious up to 6 months, also Guerreiro et al. reported that statistically significant improvement in the scores were recorded in patients who received PRP injections after 3–6 months of follow-up and van Pham et al. agreed with these findings and reported that osteoarthritic patients injected by PRP showed significant improvement at 6-month follow-up.
| Conclusion|| |
Promising results observed in these 12 months follow-up study indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy, especially in younger patients with early OA, and can avoid or at least delay the need for more invasive surgical procedures.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]