Effectiveness of dextrose prolotherapy in addition to plantar fascia stretches to plantar fascia stretches alone in the treatment of chronic plantar fasciitis: A randomized controlled trial

INTRODUCTION

The most common cause of heel pain for patients presenting to the clinic is plantar fasciitis. About 11–15% of ailments affecting the foot and 2.7–17.5% of all injuries in athletes, especially in running-related sports, are attributed to this cause.^[1-3] This condition is common in both sedentary (40–60 years) and athletic populations. Prolonged weight bearing and repeated overload of the foot in daily activities or sports attributes to the development of the condition.

Hicks first illustrated the functional shortening of the plantar fascia as the “Windlass Effect.” When the toes are extended through the propulsive phase, the plantar fascia is functionally shortened as it wraps around the heads of the metatarsals. As a result, it elevates the arch and transforms the foot into a rigid lever.^[4] During the late stance phase, the windlass effect aids in supination of the foot.^[5] This can affect running efficiency, footwear impact, and rehabilitation planning.^[6,7]

The understanding of the pathogenesis of plantar fasciitis is that repetitive microtrauma occurs at its origin on the calcaneum. These repetitive micro-injuries cause degeneration, not inflammation.^[8] Therefore, the term “fasciosis” or “fasciopathy” is more fitting. The cause of plantar fasciopathy is multifactorial.^[9] Training errors, improper footwear, and overuse are pertinent causes in runners. In sedentary adults, it is attributed to obesity, contracted gastrocnemius, low intrinsic muscle strength, or poor force attenuation, associated with acquired pes planus and compounded by the body’s decreased healing capacity.^[10-13]

The most widely used treatments include modification of activity and footwear, anti-inflammatories, stretching exercises, taping, orthosis, extracorporeal shockwave therapy (ESWT), and corticosteroid injections. However, there is insufficient evidence from high-quality randomized controlled trials for the effectiveness of other treatments.^[14,15] Tissue-specific plantar fascia stretches are one of the most basic and effective conservative ways to treat plantar fasciitis. The goal of the plantar fascia-stretching protocol is to recreate the windlass mechanism to limit repetitive microtrauma and associated chronic inflammation.^[10] Patients responding poorly to treatment often due to inappropriate, nonspecific stretching techniques or improper recommendations for shoe inserts. These patients seem to be on stretching protocols that emphasize stretching the Achilles tendon and not the plantar fascia.^[16-18]

Prolotherapy involves injecting a small volume of an irritant solution, a proliferant, at multiple sites around a ligament or tendon insertion.^[19] This solution instigates a localized inflammatory response at the site of injection, inducing fibroblast proliferation. The upregulation of various growth factors results in collagen synthesis for tissue repair.^[20] With dextrose, the proliferative response results from the higher osmolarity of the injected solution compared to the interstitial tissue; hence, it is often referred to as “hyperosmolar dextrose,” which, in a distinct concentration, causes the osmotic rupture of local cells.^[21] On exposure to various levels of glucose, the mesangial cells, smooth muscle cells, and fibroblasts stimulate the production of transforming growth factor b-1, platelet-derived growth factor, connective tissue growth factor, epithelial growth factor, and basic fibroblast growth factor.^[22-24] Dextrose prolotherapy (DPT) may reduce pain by modulating the nociceptors and decreasing neurogenic inflammation.^[25] DPT assists in reducing abnormal plantar fascia swelling and alleviating pain.^[26]

Symptoms of plantar fasciitis frequently decrease within 10 months of the use of the classical modalities, but in 10% cases, persist or get exacerbated.^[27] With few studies on the role of DPT along with tissue-specific plantar stretches on clinical outcome, the need for more research remains. In patients with chronic plantar fasciitis, how does the addition of prolotherapy to a plantar fascia stretching program affect pain and functional outcomes compared to stretching alone over 16 weeks.

MATERIALS AND METHODS

The study was a randomized controlled trial approved by the institutional review board in 2020. Consenting adult patients 18–60 years, who visited the outpatient department of a tertiary care hospital with heel pain of at least 6–8 weeks, noticeable on the first step in the morning, relieved with activity, and examination revealing point tenderness at the medial calcaneal tubercle, were enrolled in the study. Baseline blood investigations included complete hemogram, fasting blood glucose, glycosylated hemoglobin, erythrocyte sedimentation rate, and C-reactive protein to exclude patients with associated comorbid conditions such as uncontrolled diabetes mellitus and systemic inflammatory disease. Ankle radiographs were done to rule out calcaneal fractures or ankle instability. Patients who received previous interventional treatment for plantar fasciitis, including corticosteroid injections, platelet-rich plasma Injections, ESWT, or surgery, were excluded from the study.

The sample size was calculated based on the work of Ersen et al.^[28] with a pooled standard deviation of 18.85, alpha of 95% and power of 85%. It was estimated to be 23 in each group. Expecting a loss to follow-up, 30 patients were included in each group. The patients were randomized into two groups based on a computer-generated randomization sequence by a nurse not involved in participant recruitment or assessment, as illustrated in Figure 1. This was done only after confirming participant eligibility and obtaining informed consent. Group A represented patients receiving plantar fascia stretching exercise, and group B received DPT injections with plantar fascia stretching exercise. All patients underwent baseline and follow-up measurements of pain using the Visual Analog Scale (VAS) and function using foot function index (FFI) and foot and ankle outcome score (FAOS) at 6,12, and 16 weeks. Treatment and follow-up were independently carried out by two separate investigators.

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Figure 1:

The CONSORT patient enrollment flow diagram.

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All the patients (group A + group B) were taught plantar fascia-specific stretches and instructed to hold the stretch for 10 s, repeating 10 times, as illustrated in Figure 2. The stretches were to be repeated 3 times a day for 8 weeks (in accordance with DiGiovanni et al.)^[27] along with the other exercises, as illustrated in Table 1. Group A received tissue-specific plantar fascia stretches. Group B received Prolotherapy Injections - 2 injections (3.6 mL dextrose [15% solution] and 0.4 mL lidocaine),^[25] which were administered in the plantar fascia under aseptic conditions at 3-week intervals, as illustrated in Figure 3 and tissue-specific plantar fascia stretches started 72 h after injection. Patients were advised to take analgesics such as paracetamol or tramadol on need basis. No non-steroidal anti-inflammatory drugs (NSAIDs) were used. All patients were advised to wear silicone heel pads. Patients with flat feet were advised to use insoles. Patients were instructed to bring recordings of their exercise sessions for review, enabling corrections and assessment of compliance with home-based exercises.

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Figure 2:

Plantar fascia stretching exercise – Patient crosses the affected leg over the contralateral leg. The hand of the affected side is placed at the base of the toes, pulling the toes backward towards the shin until a stretch is felt in the arch of the foot. The stretch is confirmed by placing the finger of the opposite hand to feel the tension of the plantar fascia.

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Figure 3:

Dextrose prolotherapy injection. (3.6 mL dextrose [15% solution] and 0.4 mL lidocaine) administered in the plantar fascia by the palpation method under aseptic conditions.

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The dependent variables were reassessed at the end of the 6^th, 12^th, and 16^th weeks. The pain and function scores were checked for normality. They were compared at baseline and post-intervention using 2-sample t-tests. The groups were also compared at baseline for differences in age and duration of symptoms using a two-sample t-test. For gender distribution and side involvement, the Chi-squares test was used. A P < 0.05 was considered statistically significant for all tests.

RESULTS

The demographic details of the patients are described in Table 2. Sixty patients were included in the study of the 71 who were assessed.

The results of the study are described in Table 3. The groups were baseline comparable for all outcome variables. Group B had a significantly lower VAS score at 16 weeks as compared to Group A (mean difference [MD] - 0.933; 95% confidence interval [CI] - 0.138,1.728). Group B showed a significantly lower FFI at 12 weeks – MD - −7.433; 95% CI - −11.716, −3.151 and 16 weeks – MD - −7.033; 95% CI - −10.947, −3.120. Group B also showed a higher FAOS at 12 weeks – MD - −5.700; 95% CI - −9.697, −1.703) and 16 weeks – MD - −6.667; 95% CI - −10.412, −2.922, as mentioned in Table 3.

DISCUSSION

The effectiveness of DPT as a stand-alone or adjunctive treatment remains a subject of ongoing debate. In our prospective interventional study, we observed that combining prolotherapy with exercise led to superior clinical outcomes compared to exercise alone.

Most patients in our study were female homemakers. Cultural practices in India promote barefoot walking and standing for long duration while doing household chores. Males presenting to the outpatient included police officers and army personnel, with duties requiring a long duration of standing, wearing hard-soled shoes. We had 3 athletes, whose symptoms resulted from intensive training regimes.

Patients in our study had an average symptom duration of 8–9 months, with no previous interventions except NSAIDs and exercises. The addition of DPT early in our study, without exhausting other options, as opposed to Kim and Lee^[29] which had patients with symptoms for at least 6 months and had failed all previous conservative modalities, including corticosteroid injections and ESWT. Their clinical outcomes were modest. Using DPT early in the treatment, before exhausting all modalities of treatment, may result in better results and long-term pain relief.

VAS showed a falling trend in both groups, with a significant difference between groups at 16 weeks. DPT has been shown to reduce pain in 4–8 weeks and has a discernible reduction in chronic pain, usually after 12 weeks as soft-tissue healing progresses.^[30] Prolotherapy stimulates the body’s natural healing response. The fibroblasts proliferation and collagen deposition triggered by the immune response to high osmolar dextrose begin early, however the remodeling of collagen begins by about 3 weeks, steadily raising the tensile strength thereafter.^[31] Tissue-specific plantar fascia stretches aid the remodeling of the collagen process further. DPT has significant short-term (1–3 months) effects in terms of pain reduction in chronic plantar fasciitis.^[32] Seven patients in the DPT group reported a 1 on the VAS scale, 2 of whom were athletes. Males, most of whom were police officers and army personnel, showed a better reduction of pain with DPT and exercises than with exercises alone at 16 weeks. Prolotherapy and structured rehabilitation exercises could be used early in athletes, police officers, and army personnel for better long-term relief without risking side effects and the development of chronic resistant plantar fasciitis.

FFI, which is a measure of the pain and the disability caused by it, showed a falling trend with a significant difference at 12 and 16 weeks. Similarly, FAOS, which is a measure of functional outcome, showed a significant rise at 12 and 16 weeks. Both groups showed a reduction in disability due to pain; however, the DPT group showed a 34% decrease in FFI by 16 weeks. As the pain decreased, the disability associated with it decreased, and this, in turn, possibly increased the motivation to follow the exercise regime, which further improved the functional outcomes.

The use of ultrasound in injection therapies is becoming increasingly popular to increase the precision of injection into the specific area of pathology. Chen et al.^[33] compared the effectiveness of ultrasound-guided versus palpation-guided injections and concluded that results of ultrasound-guided injections surpassed the palpation-guided ones and led to less complications and increased precision. However, Kane et al.^[34] concluded that there was no significant difference and that palpation-guided injections were equally effective as ultrasound-guided ones. We used a palpation-guided technique to inject DPT into the heel at the insertion of the plantar fascia into the calcaneum.

Our study showed no side effects. Prolotherapy is proving to be an effective treatment without side effects, showing more promise than corticosteroid injections, which are found to be effective in reducing pain in the short term up to 3 months^[35] and comes with its own set of risks such as plantar fascia rupture, fat pad atrophy, infection, skin atrophy, and osteomyelitis.

DPT is a safe option in the treatment of chronic plantar fasciitis. With regenerative medicine paving the way for new ways to treat disease pathology, prolotherapy is believed to interrupt the degenerative cycle associated with tendinopathy and enable the healing process, leading to improved clinical outcomes.^[36]

The strengths of the study were that exercises were home-based, easy to perform, and did not need assistance. There were no side effects reported by the DPT group other than pain.

The limitations were that there was no placebo group, and neither the treating physician nor the patient was blinded to the treatment procedure. A small sample size and a relatively short follow-up make it difficult to determine whether early exercise initiation could be useful in the long run. Ultrasound-guided injections could have increased the precision of drug delivery to a specific area. While there was significant improvement in pain and functional outcomes, it is difficult to comment on the exact mechanism of action of DPT, whether it is dextrose or inflammation due to injury from the needle.

We used 2 injections of 15% dextrose solution given at 3-week intervals. In previous studies, researchers have used hyperosmolar dextrose with concentrations varying from 12.5% to 25% and the number of injections ranging from 1 to 12. Ryan et al.^[37] found that a median of 3 injections (range 1–12) was required for a satisfactory clinical outcome or to determine no response to treatment. Further research should be directed at standardizing the concentration, number of injections, and duration between injections with long-term follow-up.

Clinical Implication: 3 athletes were a part of our study, 2 were administered DPT before exercises. They reported a VAS of 1 at the end of 16 weeks, while in the other group, the athlete reported a VAS of 4 at the same time. Athletes and Army personnel commit to intense training regimes. Intervening with DPT mandates a break, giving the plantar fascia a chance to heal. It comes with no side effects as serious as plantar fascia ruptures that can be seen with corticosteroid injections, which could provide early but short-term symptom relief. Hence, DPT may be considered as a first-line treatment along with exercises in athletes and Army personnel.

CONCLUSION

DPT with plantar fascia-specific exercises resulted in better clinical outcomes than exercise alone in the treatment of chronic plantar fasciitis. The decrease in pain and disability (VAS, FFI) as well as improved function, as indicated by increasing FAOS in the DPT group, highlights its benefit. Using DPT early can improve clinical outcomes, especially in athletes and Army personnel who have highly demanding activities.