Orthokine – Cellpharmaco

Knee Surgery, Sports Traumatology, Arthroscopy

Injection with autologous conditioned serum has better clinical results than eccentric training for chronic Achilles tendinopathy

Lutz von Wehren1 · Kerstin Pokorny2 · Fabian Blanke3 · Jannis Sailer4 · Martin Majewski5

Received: 6 February 2018 / Accepted: 4 March 2019

Abstract

Purpose Chronic Achilles tendinopathy is one of the most common causes of malfunction and pain, which can lead to a significant reduction of the quality of life. The hypothesis of this study argues that autologous conditioned serum (i.e., Orthokine) injections in chronic midportion Achilles tendinopathy have a better outcome than eccentric training.

Methods This study investigates, retrospectively, the effects of peritendinous autologous conditioned serum injections as compared to standard eccentric training in 50 patients with chronic Achilles tendinopathy between 2012 and 2015. Before injection or eccentric training and 6 weeks, 12 weeks, and 6 months thereafter, the patients were assessed by means of the VISA-A-G score (Victorian Institute of Sport Assessment-Achilles questionnaire—German). An MRI was also performed before and 6 months after injection and eccentric training.

Results Both patient groups had statistically significant better VISA-A-G scores after injection or eccentric training compared to the baseline before injection (90 vs. 40, respectively, P < 0.001) or eccentric training (81 vs. 47, respectively, P < 0.001). Comparing the baseline corrected VISA-A-G scores, patients in the autologous-conditioned-serum group had significantly higher changes in VISA-A-G scores than the eccentric-training group after 12 weeks (40 vs. 36, P = 0.018) and 6 months (50 vs. 34, P = 0.034).

Both patient groups had statistically significant (P < 0.001) reduction of tendon thickness (autologous conditioned serum: 0.32; eccentric training: 0.24) and length of bursa (autologous conditioned serum: 0.24; eccentric training: 0.21) as well as significant (P < 0.001) improvement of tendon quality in MRI (autologous conditioned serum: 14 vs. 1; eccentric training: 14 vs. 2). There were no statistical differences in MRI findings between the two groups.

Conclusion Both therapies led to improvement of MRI findings, including reduction of tendon thickness and tendon quality. Autologous-conditioned-serum injections show greater clinical long-term benefit as compared to eccentric training and, therefore, offer a good alternative to eccentric training.

Keywords

Achilles tendinopathy · Autologous conditioned serum · PRP · Injection · MRI · Achilles tendon · Tendinosis · Biologic healing enhancement · Imaging · Growth factors/healing enhancement

Introduction

Chronic painful mid-portion Achilles tendinopathy is a relatively common condition among recreational and elite athletes, but it is also seen in non-active individuals [1]. The incidence of Achilles tendinopathy in top-level runners has been estimated between 7 and 9% [39]. Tendinopathy of the mid-portion of the Achilles tendon accounts for 55–65% of all injuries, and in approximately 20–25% of cases, an insertional Achilles tendinopathy can be diagnosed [23]. Chronic painful mid-portion Achilles tendinopathy is most common between the ages of 36 and 60 and very rare among individuals younger than 25 years [1]. The etiopathogenesis of Achilles tendinopathy is currently considered multifactorial, and the interaction between intrinsic and extrinsic factors has been postulated [22].

Disturbances of the tendon structure lead to considerable loss of function in the lower extremities [27] and, in severe cases, it can interfere with activities of daily living [22].

Eccentric muscle loading has become the dominant conservative intervention strategy for Achilles tendinopathy over the past decade [28]. Magnussen et al. showed in their review that the heavy-load eccentric exercise programme has the most evidence of effectiveness in the treatment of chronic midportion Achilles tendinopathy [26].

Only 60% of athletic and non-athletic patients benefited from eccentric training [24], and an additional therapy like injection therapy should be considered [24, 26]. Orthobiologics such as platelet-rich plasma (PRP), whole blood, or autologous conditioned serum hold promise as upcoming and novel treatment modalities [9]. Growth factors present in blood products and the potential of these growth factors to induce further release of such factors are thought to improve the healing process in chronic injuries and to accelerate repair in acute and chronic lesions [21].

Numerous studies have documented the beneficial effects of individual growth factors on tendon healing in animal models, and although the effect of growth factors on tendon healing is impressive, it has become increasingly clear that tendon repair is not triggered by a single growth factor but requires the interplay of various such factors [27]. Some improvements have been achieved and are implemented in clinical practice using such biological “cocktails with growth factors” [31].

Kearney et al. concluded in their review that there is insufficient evidence to draw conclusions on the use, or to support the routine use, of injection therapies for treating Achilles tendinopathy [15]. A recent meta-analysis found no differences in treatment of chronic Achilles tendinopathy with eccentric training in combination with either PRP or saline [52]; another recent meta-analysis revealed that injection of autologous blood-derived products in patients with Achilles tendinopathy is not more effective than placebo [19]. These findings are still debated and, therefore, highlight a need for more research in the area of injection therapies for Achilles tendinopathy.

Autologous conditioned serum provides a convenient means of applying multiple autologous growth factors [13]. Baltzer et al. reported in a study with 376 patients with knee joint osteoarthritis treated with autologous-conditioned-serum injections that treatment with the autologous conditioned serum is safe [3]. A previous study showed its beneficial effect on the healing Achilles tendon in rats [27]. In a recent study, Genç et al. confirmed these findings and stated that autologous conditioned serum may be favorable for the treatment of human Achilles tendon injuries and tendinopathies [12].

To our knowledge, the effect of autologous-conditioned-serum injections in chronic midportion Achilles tendinopathy as compared to eccentric training has not yet been investigated. Therefore, this study evaluates autologous-conditioned-serum injections vs. eccentric training in patients with chronic midportion Achilles tendinopathy.

The results should contribute to a better understanding of the role of autologous conditioned serum in the treatment of chronic midportion Achilles tendinopathy and could offer a treatment that is not dependent on the compliance of the patient for physical therapy. The hypothesis of this study argues that autologous-conditioned-serum injections in chronic midportion Achilles tendinopathy have a better outcome than eccentric training and that there is a correlation between clinical and MRI findings.

This is the first comparative study investigating the effect of autologous-conditioned-serum injections in chronic midportion Achilles tendinopathy and is the largest study comparing the structural changes in MRI between injection therapy and eccentric training in Achilles tendinopathy.

Materials and methods

Patient selection

Fifty consecutive patients (23 women, 27 men; mean age 54 ± 12 years; range 18–72 years) admitted to our hospital between 2012 and 2015 were enrolled in this study retrospectively. Before admission, all patients reduced their activities of daily living or suspended their sport activities due to their heel pain.

Inclusion criteria

Patients were included if they were ≥ 18 years, experienced persistent tenderness on palpation or distension in the mid-portion of their Achilles tendon for at least 6 weeks. An MRI must also have been performed and was evaluated by the criteria of Weber et al. [51]. MRI is the gold standard in the evaluation of tendon disorders [51].

Exclusion criteria

Excluded were patients with generalized inflammatory arthritis (e.g., ankylosing spondylitis, rheumatoid arthritis, or psoriatic arthritis), prior Achilles tendon tear, pregnancy, severe infection, malignancy, bleeding disorder, nerve-related symptoms (e.g., radiculopathy), or osteoarthritis of the ankle.

Treatment groups

The patients were divided into two groups:

1.Autologous-Conditioned-Serum Group: Received three sequential autologous-conditioned-serum injections in 7-day intervals.

2.Eccentric-Training Group: Prescribed eccentric training supervised by physiotherapists based on the Alfredson protocol [2].

Injection Procedure

For the autologous-conditioned-serum group:

•60 ml of whole blood was taken using a special syringe.

•Blood was incubated at 37°C to stimulate the production of IL-1Ra by white blood cells.

•Serum was centrifuged, filtered, and frozen in 2 ml aliquots.

•Injections were thawed and injected peritendinously into the area of maximum pain.

Patients in this group were advised to avoid sport activities for 4 weeks after injection.

Eccentric Training Protocol

Patients performed eccentric training on a step as follows:

•3 × 15 repetitions with straight and flexed knees.

•Twice a day, 7 days a week, for 3 months.

Non-steroidal anti-inflammatory drugs (NSAIDs) were not allowed during the 6-month follow-up.

Clinical Evaluation

Outcomes were measured using the VISA-A-G questionnaire (Victorian Institute of Sport Assessment-Achilles). This validated tool assesses pain, function, and activity levels. Improvement of >10 points is considered clinically significant [41].

Radiological Evaluation

MRI scans were performed at baseline and 6 months post-treatment. Evaluated parameters included:

•Tendon thickness.

•Length of subachilleal bursa.

•Tendon cross-sectional area.

MRI findings were scored on a 0–3 severity scale based on established criteria [51].

Statistical Analysis

•Data were tested for normality using the Kolmogorov–Smirnov test.

•Paired t-tests compared pre- and post-treatment values.

•Independent t-tests compared the two groups.

•Fisher’s exact test was used for categorical data.

•Spearman’s rho measured correlations between clinical and MRI outcomes.

Significance was set at p < 0.05.

Results

Patient Characteristics

•Autologous-Conditioned-Serum Group: 25 patients (mean age: 55 ± 12 years).

•Eccentric-Training Group: 25 patients (mean age: 52 ± 13 years).

Both groups showed significant improvement in VISA-A-G scores after 6 weeks, 12 weeks, and 6 months (p < 0.001).

Clinical Outcomes

•The autologous-conditioned-serum group showed greater improvement in VISA-A-G scores compared to the eccentric-training group at 12 weeks (p = 0.018) and 6 months (p = 0.034).

•Significant improvement in tendon thickness and MRI findings was observed in both groups (p < 0.001).

MRI Findings

Both groups demonstrated significant improvements in MRI outcomes:

•Reduction in tendon thickness (A4).

•Decrease in bursa length (A5).

•Reduction in tendon cross-sectional area (F).

•Improved tendon quality (R).

There were no significant differences in MRI results between the two groups.

Correlations

•A negative correlation was found between reduction in tendon thickness (A4) and improvement in VISA-A-G scores (ρ = -0.279, p < 0.05).

•No significant correlations were found for other MRI parameters.

Discussion

The main findings of this study show:

1.Both autologous-conditioned-serum injections and eccentric training yield significant clinical improvements in patients with Achilles tendinopathy.

2.The autologous-conditioned-serum group demonstrated greater improvement in VISA-A-G scores at 12 weeks and 6 months compared to the eccentric-training group.

Clinical Implications

•Autologous-conditioned-serum injections offer a viable alternative to eccentric training.

•This therapy is less dependent on patient compliance with physical therapy protocols.

Comparison with Previous Studies

•Eccentric training is widely accepted as the standard treatment for Achilles tendinopathy [2, 25].

•Prior studies showed variable results with eccentric training in terms of tendon thickness and return to physical activity [14, 32, 48].

•Autologous-conditioned-serum injections have demonstrated clinical benefits, but MRI findings did not show significant differences between the two therapies.

Limitations

•Lack of randomization and blinding in this study.

•Absence of a placebo control group (e.g., saline injections).

•Short follow-up duration (6 months).

Conclusion

This study suggests that autologous-conditioned-serum injections are favorable compared to eccentric training in treating chronic midportion Achilles tendinopathy.

•Clinical benefits were observed at 3 and 6 months post-treatment.

•Further randomized controlled trials with larger sample sizes and longer follow-ups are recommended.

Acknowledgements

The authors thank Mrs. Muth and Mrs. Herdt for their support and proofreading.

Funding

No funding was received for this study.

Conflict of Interest

The authors declare no conflicts of interest.

References

(Details of all references cited in the study)