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Efficacy of Shock Waves Combined with Adjuvant Therapy with Tendon Supplement in the Treatment of Plantar Fasciitis: A Prospective Randomized Study

Angela Notarnicola*, Lorenzo Moretti, Marco Baglioni, Ilaria Covelli, Francesco Paolo Bianchi, Aurora Citraro, Biagio Moretti

Orthopedics Section, Department of Medical Sciences of Basis, Neurosciences and Organs of Sense, Faculty of Medicine and Surgery, Aldo Moro University of Bari, Bari, Italy

Abstract: Physical treatment with focused shock waves is effective in the treatment of tendonitis in 60-90% of cases. Plantar fasciitis is attributable to the group of tendon pathologies for its degenerative-inflammatory anatomopathological characteristics. Food supplements could facilitate the healing of tendinopathies when combined with shock wave therapy. We designed a single-blind, randomized prospective study (level of evidence IB). Forty-four patients with plantar fasciitis were recruited and randomized to group A (18 patients) and group B (26 patients), where they were treated with focused shock waves alone and the combination of focused shock waves and tendon supplement, respectively. Statistically significant improvement in pain remission (primary endpoint) and functional recovery (secondary endpoint) occurred in both groups at three time points of the monitoring (Months 0, 3, and 6). The time-group interaction analysis confirmed the best efficacy of the combination treatment with shockwave and supplement (group B). The results of this study demonstrate a positive therapeutic effect of the combination of focused shock wave therapy and a complex tendon supplement in the treatment of plantar fasciitis.

Keywords: focused shock waves, tendinitis, nutraceuticals, plantar fasciitis

Received February 03, 2021; Revised March 09, 2021; Accepted March 18, 2021

Citation: Angela Notarnicola, Lorenzo Moretti, Marco Baglioni, Ilaria Covelli, Francesco Paolo Bianchi, Aurora Citraro, Biagio Moretti, Efficacy of Shock Waves Combined with Adjuvant Therapy with Tendon Supplement in the Treatment of Plantar Fasciitis: A Prospective Randomized Study. Journal of Food and Nutrition Research, 9 (3). 148-153. January 2021. doi:10.12691/jfnr-9-3-7

1. Introduction

Plantar fasciitis is a common degenerative and inflammatory pathology affecting the plantar fascia and has several similarities with tendinopathy [1]. About 10% of the population had this disease, which is more common in women between the ages of 40 and 70 [2], and it progresses into chronic pain in 10-20% of cases [1]. This condition is often positively managed with conservative treatments, such as physical therapies, systemic non-steroidal anti-inflammatory drugs, local corticosteroid injections, unloading with shoe inserts. However, in non-responder cases, plantar fascia release surgery with the regeneration of the calcaneal bone-tendon junction can be recommended [3,4,5,6].

Structurally, tendons and musculotendinous fasciae are composed of a cellular part and a fibrillar part surrounded and located in an extracellular matrix [7]. The cells are mainly fibroblasts and produce the extracellular matrix components: collagen fibers, elastin fibers, and proteoglycans. When a patient presents with tendinopathy or fasciitis, the degenerative component tends to prevail or alternates with the inflammatory component. The most important biohistochemical changes of the microenvironment include hypoxia with cell necrosis, an increase of metalloproteinases that stimulate the degeneration of the matrix, over-production of inflammatory cytokines, the predominance of type III over type I collagen fibers resulting in more significant ultrastructural disorganization of the fibers, increased VEGF expression that promotes local neoangiogenesis and progressive calcific metaplasia which replaces the degenerated tissue [8].

Extracorporeal focused shock wave therapy (ESWT) has recently become very popular and is used to treat many soft tissue disorders [9]. The shock waves can be characterized by a rapid rise in pressure, followed by an equally rapid descent in a short period of time, which justifies its cavitation effect. One potential benefit is that the flow of energy is focused on a small area where the neoangiogenic, revascularizing, analgesic, inflammation modulation, and proliferative therapeutic effects will be concentrated [10].

In recent years, the use of nutraceuticals has been suggested to support the physiological turnover of tendon to counteract and modulate inflammation and local degeneration [11] using numerous tendon-protective substances such as arginine, methylsulfonylmethane, collagen, vitamin C, vitamin D, amino acids, bromelain, glucosamine, and chondroitin sulfate [12,13,14]. Several studies suggest that oral supplements increase the precence of these compounds in the tendon context and may help preserve the damaged structures [15]. Their efficacy has been demonstrated by pre-clinical studies and randomized controlled trials (RCTs) [16], but few have verified the efficacy of focused shockwaves combined with food supplements.

This study aims to verify whether combination treatment with shock waves and tendon supplement is efficient on pain (primary endpoint) and can achieve a better functional recovery (secondary endpoint) in patients with plantar fasciitis.

2. Materials and Methods

2.1. Study Design and Population

We designed a prospective randomized, single-blind study with an evidence level of 1B, which was approved by the local Ethics Committee (number 5980 on 11.09.2019) and registered at ClinicaTrials.gov (NCT04664712). The subjects enrolled signed informed consent.

Forty-four patients were enrolled at the Osteoporosis-Densitometry-Shockwave Outpatient Clinic of the Orthopedics and Traumatology Unit of the "Policlinico" University Hospital of Bari. Of these patients, 18 and 26 patients were randomized in Groups A (shock wave therapy) and B (shock wave therapy and tendon supplement), respectively. In these two groups, the randomization criteria were applied using a predefined program (http://www.randomization.com).

The inclusion criteria were: plantar heel pain diagnosed clinically and by ultrasound as plantar fasciitis, that has not responded to conservative treatment for at least six months; age between 18 and 80 years.

Exclusion criteria were: history of previous fractures or ankle and heel surgery; recurrence of previous local painful episodes; lesion of the plantar fascia on ultrasound examination; presence of pathologies that affect the function of the foot (lumbar radiculopathy, Achilles tendinitis, Morton's neuroma, etc.); chronic inflammatory conditions such as psoriasis, psoriatic arthritis, spondyloarthritis, ankylosing spondylitis, rheumatoid arthritis, chronic inflammatory bowel disease.

2.2. Treatment Protocol

Both groups received ESWT treatment delivered with an electromagnetic generator equipped with ultrasound probe (Minilith SL 1, Storz, Swiss). The patient was placed in a prone position, and the calcaneal insertion of the plantar fascia was identified under ultrasound guidance. We performed three sessions with a weekly interval. We delivered 2000 shots per session using a low/medium energy level (range between 0.01 and 0.175 mJ/mm2) depending on the patient's tolerance during treatment with a frequency of 4 Hz.

Group A patients received ESWT treatment alone, and Group B received ESWT treatment combined with a treatment cycle with a complex dietary supplement based on Methylsulfonylmethane (2.5 g), hydrolyzed collagen (1 g), L-arginine (1 g), L-lysine (500 mg), Vitamin C (500 mg), Bromelain (200 mg), Chondroitin sulfate (150 mg), Glucosamine (150 mg) [17,18], dry extracts of turmeric (100 mg), Boswellia (100 mg) and Myrrh (50 mg) (TENDISULFUR® PRO, Laborest, Italy). The supplement was administered at the dosage of one sachet twice a day for an initial period of 30 days, and then one sachet per day for an additional 60 days.

The evaluation times were T0 (recruitment), T1 (after three months) and T2 (after six months). At recruitment (T0), epidemiological (age, weight, BMI, gender, smoking), anamnesis and clinical data (mode of onset of pain, previous therapies, instrumental examinations, co-morbidities, etc.) of the patients were collected. VAS, AOFAS, Foot Function Index (FFI) evaluation scales were administered at each evaluation moment. At T1 and T2, the Roles and Maudsley Score was also administered.

As a primary endpoint, pain was quantified using the VAS scale with scores ranging from 0 (no pain) to 10 (worst imaginable pain).

As a secondary endpoint, the functional recovery was monitored using the American Foot & Ankle Score (AOFAS) with the scores ranging from 100 (no disability) to 0 (maximum disability) and the Foot Function Index (FFI) with the scores ranging from 100 (no disability) to 0 (maximum disability).

In addition, the Roles & Maudsley (R&M) scale administered only at follow-up visits allowed the monitorization of the patient's perception of improvement, with the scores ranging from 1 (excellent) to 4 (minimum).

2.3. Methods

The collected data were analyzed using “Stata MP16” software.

Continuous variables were expressed as mean±standard deviation and range, and categorical variables as proportions.

The normality of continuous variables was evaluated and a standardization model was set for those not normally distributed. Continuous variables were compared between groups using the Student t test for independent data or the Wilcoxon rank-sum test, while the ANOVA test for repeated measures was used for comparison between groups and detection times. Categorical variables were compared using the chi-square test or Fisher's exact test.

Univariate linear regression was used to evaluate the correlation between the differences in VAS, AOFAS, FFI between T2 and T0 and R&M between T1 and T2 and various determinants. Subsequently, some multivariate linear regression models were set up between the single outcome and the group variable (group B vs. group A), adjusted for age at enrollment and those determinants resulted associated in the univariate regression. The correlation coefficients were calculated with reference to a 95% confidence interval (95% CI).

A p-value <0.05 was considered significant for all tests.

3. Results

3.1. Characteristics of the Study Population

The study sample includes 44 subjects, of which 18 (40.9%) are included in Group A, and 26 (59.1%) in Group B. Table 1 describes the characteristics of the sample.

The outcomes evaluated by detection time and group demonstrate a statistically significant difference for time for VAS, AOFAS and FFI and time-group interaction for VAS and AOFAS (Table 2). For R&M, a statistically significant difference is detected in the comparison between groups.

The comparison between groups of the outcomes, evaluated per single revelation time, is described in Table 3.

The univariate analysis between the determinants (gender, age, side, smoking, previous therapies, treatment, BMI, onset of symptoms) and the difference in VAS between T2 and T0 demonstrated a statistically significant difference for smoking (coefficient -3.6, 95% CI: -6.3 - -0.8, p: 0.012) and for BMI (coefficient 0.3, 95% CI: -0.4- -01, p: 0.007); the multivariate analysis confirmed the association with BMI (coefficient 0.21, 95% CI: 0.03-0.39, p: 0.027) and smoking (coefficient -2.60, 95% CI: -5.22 – 0.02, p: 0.051; limits of statistical significance).

Table 1. Characteristics of the sample by group (Group A vs. Group B). Statistically significant values are indicated with *

Table 2. Description of outcomes by group (Group A vs. Group B) and time of detection

Table 3. Comparison between groups of VAS, AOFAS, FFI and Roles & Maudsley

The univariate analysis of the determinants of the difference in AOFAS between T2 and T0 showed a statistically significant difference for groups (coefficient 15.1, 95% CI: 4.3-25.9, p = 0.007) and BMI (univariate analysis: coefficient -1.7, 95% CI: -2.8 - -0.6, p = 0.004); the multivariate analysis confirmed the association with groups (coefficient 11.1, 95% CI: -0.2-22.3, p: 0.054; limits of statistical significance) and BMI (coefficient -1.33, 95% CI: -2.5 – -0.2, p: 0.021).

The univariate analysis of the determinants of the difference in FFI between T2 and T0 showed a statistically significant difference for smoke (coefficient -29.8, 95% CI: -51.0 - -8.6, p = 0.007) and BMI (coefficient 1.6, 95% CI: 0.2-3.1, p = 0.030); the multivariate analysis only showed a statistically significant difference with smoking (coefficient -23.9, 95% CI: -45.0 - -2.7, p: 0.028).

The univariate analysis of the determinants of the difference in R&M between T1 and T2 shows a statistically significant difference for smoke (coefficient -0.9, 95% CI: -1.7 - -0.1, p = 0.033) and BMI (coefficient 0.08, 95% CI: 0.03-0.13, p = 0.002); the multivariate analysis only showed a statistically significant difference with BMI (coefficient 0.07, 95% CI: 0.02-0.13, p = 0.010).

Figure 1. CONSORT 2010 Flow Diagram

4. Discussion

The most important finding of our study was that the combined effect of a tendon supplement and focused shockwaves achieved a better therapeutic response in the treatment of plantar fasciitis.

These results are consistent with the known biological effects of shock wave therapy and the components present in the supplement. Vitali et al. [19] showed on three different models of tendinopathy (epicondylitis, Achilles tendinopathy and rotator cuff) that a combined treatment of tendon supplement (Tendisulfur Forte) and ESWT is more efficient on pain at a follow-up at 60 days compared to shock wave treatment alone. Similarly, our previous study emphasized the efficacy of daily administration of a dietary supplement containing arginine, Vinitrox, collagen, methyl-sulfonyl-methane, vitamin C, and bromelain in combination with ESWT in the treatment of Achilles tendinopathy [20]. Focused shock waves promote tenocyte differentiation and collagen synthesis, reduce the production of interleukins and metalloproteases that damage tendons, trigger the release of endorphins and growth factors that play a mitogenic and anabolic role, and increase the blood flow [21]. The experiences described in the literature in recent years show a marked increase in the use of nutraceuticals, especially in the athlete population, to reduce the pain and prevent injuries [22], in particular, based on their ability to modulate inflammation. Preclinical results are intresting, but need to be confirmed by clinical studies. The few clinical papers on the use of nutraceuticals in tendon disorders characterized by poor methodology. In these studies more supplements were administered together. This may bias the results, and the effect of each single component cannot be defined. Furthermore, the interactions between nutraceuticals and drugs, or other dietary supplements has not been evaluated, neither their effects on chronic diseases. Therefore, so far the researchers have not attributed any definitive recommendations on the use of nutraceutical supplementation in tendinopathies. Methylsulfonylmethane has an efficient anti-inflammatory, analgesic and anti-oxidant effect [23,24]. Collagen, which is an important constituent of the tendon, improves tissues' mechanical properties [23,25,26]. Chondroitin sulfate increases collagen synthesis and improves its ultrastructural organization [27]. Vitamin C is a co-enzyme of proline hydroxylase, stimulates the synthesis of procollagen, and contributes to the normal formation of type I collagen, inducing anti-inflammatory, neo-angiogenic and anti-oxidant effects [28]. Boswellia inhibits pro-inflammatory cytokines and modulates the activity of metalloproteases [29]. Turmeric has anti-oxidant activity and modulates the transcription of numerous inflammation modulators [30,31]. L-arginine and L-lysine are essential amino acids involved in the synthesis of elastin and collagen [32,33]. Myrrh inhibits the inflammatory activation of macrophages [34]. Bromelain has anti-edema, anti-oxidant and immunosuppressive effects [35].

A possible mechanism to explain our findings is nutraceuticals can therefore contribute to the healing of tendinopathies when combined with focused shock waves, in the light of synergistic biological actions. Furthermore, ESWTs could increase the bioavailability of tendon supplements thanks to the proven neo-angiogenic properties.

A limitation of this study is the absence of instrumental monitoring (ultrasound, MRI) at follow-ups. On the other hand, an in-depth examination of the effects of a supplement composed of different substances must be underlined as a strength of the research. Other limitations of the study are the lack of homogenization by age of the two groups and the presence of high BMI values, which could affect the therapeutic response of the tendons.

5. Conclusions

The results of this study demonstrate a positive therapeutic effect of the combination of focused shock wave therapy and a complex tendon supplement in the treatment of plantar fasciitis. Therefore, we believe more studies could support the effectiveness of the combination of physical therapies and supplements.

Funding

This study was funded by Uriach-LaborestR (e-mail: info@laborest.com) which provided the food supplement free of charge used in this study and made themselves available to cover the costs of publication.

Conflicts of Interest

The authors declare that they have no conflict of interest.

Abbreviations

The following abbreviations are used in this manuscript:

VEGF Vascular Endothelial Growth Factor

ESWT Extracorporeal Focused Shock Wave Therapy

RCTs Randomized Controlled Trials

T0 TIME 0 recruitment

T1 TIME 1 (after three months)

T2 TIME 2 (after six months)

VAS Visual Analogic Scale

AOFAS American Foot & Ankle

FFI Foot Function Index

R&M Roles & Maudsley

p p Value

ANOVA Analysis of Variance

CI Confidence Interval

n Number

SD Standard Deviation

BMI Body Mass Index

MRI Magnetic Resonance Imaging

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