Safety and feasibility of locoregional platelet-rich plasma injection for iliopsoas impingement after total hip arthroplasty: A phase 1 prospective observational study

Abstract

Introduction

Although numerous studies have reported outcomes with various conservative approaches for the iliopsoas impingement after total hip arthroplasty (THA), reports on the use of locoregional autologous platelet rich plasma (PRP) injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA.

Materials and methods

Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index, Japanese Hip Disease Evaluation Questionnaire, and Forgotten Joint Score-12.

Results

Three patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male. All patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, or subcutaneous haemorrhage owing to the administration of locoregional PRP. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection.

Conclusion

We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

Highlights

• •Impingement of the iliopsoas tendon following THA is a potential cause of persistent groin pain.
• •Reports on the use of locoregional autologous PRP injections for the iliopsoas impingement after THA are lacking.
• •This study confirmed that locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.
• •A further study of this procedure should be conducted in the future.

1. Introduction

Impingement of the iliopsoas tendon following total hip arthroplasty (THA) is a potential cause of persistent groin pain and has considerable impact on activities of daily living that involve active hip flexion [1,2]. The condition is most commonly related to acetabular cup size and placement; but, excessive osteophyte formation, retained cement, and a prominent femoral collar have also been found to be responsible [3].

In the clinical situation, iliopsoas impingement is usually diagnosed in patients with continuing groin pain after THA, with the pain increased during extension and elevation of the affected lower limb; the necessity for support of the affected limb during active flexion, and a positive xylocaine test are also considered to be indicators of the condition.

Existing treatment options for the condition include conservative management, tenotomy, and acetabular revision. Although studies indicate that surgery offers higher success rates of up to 94 %, and greater improvement in Harris Hip Scores, these procedures are associated with greater risk than conservative management, which avoids the need for repeat surgery and leads to resolution of symptoms in up to 50 % cases [[2], [3], [4]]. Conservative management is therefore considered as first line therapy in many cases. In this context, a risk-benefit imbalance and the lack of effective conservative treatments are the major disadvantages of available standard therapy; further investigation is therefore needed into the use of newer treatments for the successful management of this under recognized condition.

Locoregional autologous platelet-rich plasma (PRP) injections have been increasingly used for the management of orthopaedic sports injuries and musculoskeletal conditions owing to the relative safety of the procedure, and the potential of PRP in soft tissue healing [5]. Growth factors and cytokines found in PRP potentially reduce inflammation and induce tissue regeneration; they also promote repair [6,7], and are key elements in the modulation of the tissue microenvironment at the site of injury [[8], [9], [10], [11]]. Notably, PRP injections have gained popularity in the treatment of hip and pelvic musculoskeletal conditions, and have been successfully employed in cases of osteoarthritis of the hip joint and locoregional tendinopathies. Various studies have also used PRP in the management of avascular necrosis of the hip, hamstring injuries, and avulsion of the sartorius [[12], [13], [14], [15], [16], [17]].

Although numerous studies have reported outcomes with various conservative approaches, reports on the use of locoregional autologous PRP injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA.

2. Methods

2.1. Ethical considerations

This prospective phase 1 open-label observational study was conducted at the Juntendo university hospital. The study was performed as a “class III regenerative medicine” protocol, as permitted under Japan's Act on the Safety of Regenerative Medicine. The study protocol was approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University (certification number: NA8140003) and submitted to the Ministry of Health, Labour and Welfare. Written informed consent was obtained from each participant, and the study was performed in accordance with the Act on the Safety of Regenerative Medicine and the tenets of the Declaration of Helsinki. The study was registered in the Japan Registry of Clinical Trials (jRCTb030190272).

2.2. Objectives and endpoints

This prospective phase 1 single-institution study aimed to evaluate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Japanese Hip Disease Evaluation Questionnaire (JHEQ) [18], and Forgotten Joint Score-12 (FJS-12) questionnaires [19].

2.3. Eligibility criteria

The diagnosis of the iliopsoas impingement was defined as continuing groin pain after THA, with the pain increased during extension and elevation of the affected lower limb, the necessity for support of the affected limb during active flexion, and a positive xylocaine test [1,2]. Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. However, those who were medically considered to have a higher than normal incidence of complications, such as those with a history of heavy smoking or myocardial infarction, were not eligible to participate. In addition, those who did not meet the acceptance criteria for the PRP preparation room based on viral tests, or those who did not meet the participation criteria based on the results of blood sampling tests were not eligible to participate. Details pertaining to the inclusion and exclusion criteria have been presented in Table 1. A total of 3 patients were included in this phase 1 study, based on the availability of suitable patients.

Table 1.

Inclusion and exclusion criteria for the study.

Inclusion Criteria (when all of the following are met)

1) Persistent symptom 3 months or more.

2) Persistent symptom even if taking a NSAIDs for 6 weeks or more, or not able to take NSAIDs for medical reasons such as an asthma or a gastrointestinal ulcer

3) 20 years old or more.

4) Other patients who judged as suitable participants by the attending physician.

Exclusion criteria (if any of the following are met)

1) Patients with abnormal platelet counts in peripheral blood.

2) Patients with past and/or current history of heavy smoking (Brinkman index >600) (Brinkman index = number of cigarettes per day x years)

3) Patients taking anticoagulation drugs

4) Patients with poor glycemic control (HbA1c > 9.0)

5) Patients with malignant neoplasms currently under treatment

6) Patients less than 6 month after myocardial infarction or cerebral infarction

7) Patients with a life expectancy less than 1 year due to comorbidities

8) Patients with active infection (including HBV, HCV, HIV, syphilis)

9) Patients on dialysis

10) Patients of compromised host.

11) Patients taking a drug which has a possibility to immunosuppression.

12) Patients less than 20 years old.

13) Other patients who are judged as unsuitable participants by the attending physician.

2.4. Study period

The total duration of this study extended for approximately 13–14 weeks. This included a pre-treatment period of 1–2 weeks, during which patients were provided with a detailed explanation of the study. Eligibility was confirmed during this period and written consent was obtained prior to registration. The entire process of PRP administration (through blood collection, centrifugation, and administration) lasted for 1 day. This was followed by a post-procedure observation period of 12 weeks. The 3-month follow-up period after PRP administration was used to evaluate the appropriateness of providing treatment. In particular, assessments for adverse events and dysfunction at weeks 2, 4, 8, and 12 were used to confirm safety. Pain, hip function, and quality of life assessments were used to confirm efficacy.

2.5. Preparation and administration of PRP

Approximately 20 mL of venous blood was drawn from the participants' antecubital vein on the day of the procedure. The sample was then centrifuged for retrieval of the middle layer containing the 2∼3 mL of PRP according to the manufacturer's instructions. In brief, venous blood was aspirated into the two sets of MyCells kit syringes containing 1 mL of anticoagulant dextrose solution A and separation gel. Next, the samples were centrifuged for 7 min at 2000 g. After aspirating the supernatant platelet-poor plasma, the residual 2.0–2.5 mL of plasma was pipetted to peel off the platelets from the surface of the separation gel. The filter column was then inserted into the separation syringe to remove the debris and filtered PRP. The PRP obtained using this method is classified as P2-B  PRP (leucocyte-poor (LP)-PRP) based on the PAW classification system [20]. Then the PRP was injected at the site of contact between the iliopsoas muscle and the anterior protrusion of the implant or osteophyte under fluoroscopic and ultrasound guidance (Fig. 1).

Fig. 1.

Left: X-ray in patient 1. Right: X-ray with the illustration of the injection. The contact area between the iliopsoas muscle and the anterior protrusion of the implant was confirmed by fluoroscopic and ultrasound guidance.

3. Results

Between September 2019 and March 2021, 3 patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male (Table 2). On investigation, forward protrusion of the acetabular cup was found to be responsible for iliopsoas impingement in the female patient aged 66 years. In contrast, osteophyte formation was found to be the cause of symptoms in the other two cases (Fig. 2).

Table 2.

Patient characteristics.

	P01	P02	P03
Age	66	65	73
Sex	Female	Female	Male
Height (m)	1.48	1.40	1.77
Weight (Kg)	74.5	48.3	72.0
BMI	34	24.6	23
Time from THA	6 yrs	5 yrs	4 yrs
Possible reason for the iliopsoas impingement (Fig. 2)	Anterior cup protrusion	Osteophyte	Osteophyte

Fig. 2.

X rays (1A: Paitens 1, 1B: Patient 2, 1C: Patient 3) and CT scan images (1D: Paitens 1, 1E: Patient 2, 1F: Patient 3)). Black triangle indicates the area responsible for the inflammation (1D: Anterior cup protrusion, 1E: Osteophyte, 1F: Osteophyte).

3.1. Primary endpoints

As shown in Table 3, all patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, syncope, or subcutaneous haemorrhage owing to the administration of locoregional PRP.

Table 3.

Adverse events.

Primary endpoint
Patients	Adverse event	Detail	Serious or non serious
P01	Pain	Temporary pain at injection site.	Non serious
	Chest discomfort	Chest discomfort at 3 days after the injection. No organic disease detected.
	Colonic diverticulitis	Colonic diverticulitis at 2 month after the injection.
P02	Pain	Temporary pain at injection site.
P03	Pain	Temporary pain at injection site.

3.2. Secondary endpoints

As shown in Fig. 3, all patients showed decreased pain-VAS score after the injection and more than 20 % reduction at final at 12w. Two patients demonstrated 50 % pain relief at 8 weeks, even though those effect decreased at 12 w. Concerning about the PROs (Fig. 4, Fig. 5, Fig. 6), patient 1 showed great improvement in JHEQ total score after the injection. On the other hands, 2 patients showed only slight improvement in JHEQ total score. WOMAC score did not differ after the injection in three patients. Although the score of FJS-12 was improved in all patients, the ratio of improvement more than 20 % was seen in only two patients at the final follow up of 12 w. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection.

Fig. 3.

Individual scores for the pain and improvement ratio.

Fig. 4.

Individual scores for the PROs (JHEQ, WOMAC, and FJS-12) and improvement ratio.

Fig. 5.

Individual scores for the JHEQ subscale scores.

Fig. 6.

Individual scores for the WOMAC subscale scores.

4. Discussion

Although numerous studies have reported benefits of PRP, reports on the use of locoregional autologous PRP injections for the iliopsoas impingement after THA are lacking. The findings from this preliminary phase 1 prospective observational clinical study indicate that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

The results from this cohort indicate that future studies may be undertaken for safety validation and evaluation of efficacy of this treatment approach. Although conservative management is often considered as the first option in most patients, there are numerous challenges that hinder their success. It is therefore essential that newer approaches are developed based on improved understanding on the pathophysiology of the condition. The presumed cause of pain in cases of iliopsoas impingement following THA is attributed to inflammation due to physical irritation and the injured iliopsoas muscle itself. Conservative therapy should ideally ensure that the anti-inflammatory effect following treatment is prolonged, and risks of infection are not increased; ideal conservative approaches should also promote tissue repair. As newer treatment methods are being explored based on the results of standard treatment and pathological hypothesis, it is essential that these criteria are fulfilled.

In the development of PRP treatment for psoas impingement after THA, it will be necessary to consider the following points according to the pathology of the disease. Firstly, an optimization of injectable substance and methodology are well determined. Although many different type of PRP are commercially available recently [20,21], a composition of growth factor and protease concentrations are different [22,23]. In the psoas impingement, it is necessary to stop continuous chronic inflammation and repair the iliopsoas itself. Unfortunately, our cases except for patient 2 demonstrated a persistent groin pain after the injection. Thereby, greater anti-inflammatory composition might need for this pathology. Moreover, since the occurrence of infection may cause terrible consequences leading to peri-prosthetic joint infection, the method needs minimum risk for the infection is encouraged, such as a single injection is an ideal. Second, in view of the variable outcomes recorded with different evaluation questionnaires, it is also essential that multiple evaluation methods are employed. The symptom is not always detected by the standard questionnaire. In our three patients described that the frequency of the pain and maximum range of active flexion are improved, even though it was temporary. Lastly, as patients with different findings on imaging had similar physical findings in this cohort, it appears necessary to establish multi-center research systems to ensure that diagnoses are clarified, and treatment indications are carefully assessed.

Although the findings from this prospective study will provide a reference for future studies in this area, the scope of the findings is limited by the small sample size. In addition, all patients enrolled in this cohort were from a single center; further large-scale studies including more diverse populations are therefore needed to validate our findings.

5. Conclusion

We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

Funding

This study was funded entirely by Juntendo University and no funds were used from any specific company.

Declaration of competing interest

None.