Prolotherapy for Achilles Tendinopathy

Abstract

Background: Prolotherapy (proliferative therapy) is a nonsurgical regenerative injection technique that introduces small amounts of hyperosmolar dextrose to the site of painful or degenerated tendons or their insertions. Under ultrasound guidance, a 25-gauge needle is used to fenestrate and inject hyperosmolar dextrose into the injured area of the Achilles tendon. This is found to induce the proliferation of new cells, allowing the regeneration of healthy tissue. The purpose of this study was to evaluate the treatment response to prolotherapy in Achilles tendinitis. Methods: We reviewed 132 participants with nontraumatic Achilles tendinopathy. Data were collected retrospectively from electronic health records from January 1, 2014, to December 31, 2017. These participants have Achilles tendinopathy from daily activity. We excluded any traumatic cause, history of Achilles tendon rupture, and tendon pathology. Participants were followed for 12 months; those lost to follow-up were excluded. The duration of pathology, number of prolotherapy sessions, and outcome data were recorded. Musculoskeletal radiologists performed the prolotherapy. We received an exemption from the institutional review board of Boston Medical Center for this study. Results: One hundred thirty-two participants (45 men and 87 women) met the study’s criteria, with a mean age of 55 years (range, 21–80 years). Overall, within 12 months, 98 participants (74.2%) experienced symptom resolution. Seventy-one participants (53.8%) experienced symptom improvement with a single treatment. Thirty-four participants (25.8%) still had symptoms after 12 months. Conclusions: This study demonstrated that prolotherapy yielded excellent results for Achilles tendinitis, particularly for participants without skeletal deformities. No adverse events were reported during the 12-month study. A prospective, comparative, and randomized controlled study with long-term follow-up is needed to determine the efficacy of prolotherapy.

The Achilles tendon (AT) complex is derived from a fusion of the soleus, medial and lateral gastrocnemius, and plantaris muscles. The gastrocnemius consists mainly of fast-twitch muscle fibers; it flexes the knee, plantarflexes the ankle, and inverts the subtalar joint. The soleus is a postural muscle primarily composed of slow-twitch muscle fibers. It helps keep the body upright in stance and prevents it from falling forward during gait [1]. The AT is the thickest tendon in the human body, with the ability to resist large tensile forces. This tendon is called the calcaneal tendon, referring to its attachment [2]. The AT does not have an actual synovial sheath. It is surrounded by a paratenon, which can stretch to 2 to 3 cm with movement, allowing for gliding action. Contraction of the gastrocne- mius and soleus muscles translates a force through the AT, causing plantarflexion of the foot. For activities such as walking, running, and jumping, the AT is subject to the highest loads, with tensile loads up to ten times the body’s weight [2]. Although the AT is the strongest in the body, it is prone to injury, leading to tendinopathy.

Achilles tendinopathy (ATP) is one of the most common overuse injuries affecting the Achilles tendon, which is located in the foot and ankle [3]. It comprises tendinitis, tendinosis, paratendinitis, enthesopathy, and insertional tendinitis. Due to the increased number of people participating in physical activity, ATP levels have risen [4]. The symptoms of ATP are swelling, difficulty walking, and impaired performance.[5] Tendinitis describes chronic symptoms in the tendon, implying inflammation as a cause [6]. A systemic review suggests that ATP is a degenerative condition, not an inflammatory one [7]. Treatment modalities aimed at inflammation have short-term success [8]. The terminology is changed to tendinopathy [9]. Histologic studies of surgical specimens show degenerative lesions with absent or minimal inflammation [10]. The most common cause in athletes is excessive loading with inadequate recovery time between training sessions [11]. Many intrinsic and extrinsic factors contribute to ATP [12].

Symptoms arise from overuse but can occur in overweight individuals with no history of increased physical activity [13]. The location of symptoms on palpation helps distinguish between insertional and midportion pathology, and for the differential diagnosis [12]. Differential diagnoses for participants with posterior ankle symptoms are acute AT rupture, accessory soleus muscle, sural nerve irritation, fat pad irritation, and systemic inflammatory disease [14]. Examination should include the participant’s gait, limb-length discrepancy, ankle stability, tenderness on tendon palpation, symptoms with ankle range of motion, tendon thickness, crepitus over the tendon, pes planus, pes cavus, foot malalignment, properly fitted footwear, shoe wear pattern, and Thompson test. Palpation at the insertion of the AT to the calcaneus can appreciate the bump and illicit symptoms; we refer to this as insertional Achilles tendinopathy (IAT). Pain can be located above the calcaneus insertion; we refer to this as midportion Achilles tendinopathy (MAT). Signs on palpation of this area have sensitivity of 84% for diagnosing MAT [15]. The posterosuperior of the calcaneus can have considerable prominence and is known as Haglund. Radiographic examinations and signs of pain in this area are referred to as Haglund syndrome (HGS) in this review. Patrick Haglund first described HGS in 1927 [16]. Some authors incorrectly described HGS as an enlargement at the calcaneus attachment of the Achilles and associated it with IAT and retrocalcaneal bursitis [17]. The initial workup should include a radiographic evaluation of the IAT and HGS. Ultrasonography and magnetic resonance imaging may be required to assess tendon rupture or to exclude other musculoskeletal disorders [18].

The management of ATP lacks evidence-based support, putting participants at risk for long-term morbidity because of unpredictable clinical outcomes [19]. Nonsteroidal anti-inflammatory drugs are commonly used; they may provide some symptom relief, but do not result in sustained improvement in the healing process and may interfere with healing processes [20]. The study also showed no statistically or clinically significant differences between the topical anti-inflammatory gel and placebo groups for AT [21].

Several modalities, including physical therapy, orthotic devices, taping, topical agents, dry needling, corticosteroid injections, glucocorticoid injections, platelet-rich plasma injections, and lowenergy shockwave treatment, were used. Exercise was often recommended. A systematic review favored eccentric exercise over concentric exercise for reducing symptoms; however, there was no significant difference in symptoms or function between eccentric exercise and heavy, slow resistance exercise [22]. This study did not recommend splints or orthoses to improve symptoms and function in ATP. Corticosteroid injections were effective in the short term. Still, this effect was reversed in the intermediate and long term [23]. A single-center, double-blinded, placebo-controlled, randomized trial was performed to determine whether shockwave therapy combined with eccentric exercises improves symptoms and function. At the 24-week evaluation, there was no difference in the outcome between the shockwave therapy and control groups [24]. A blinded, multicenter, randomized clinical trial was performed to evaluate platelet-rich plasma injection versus a sham injection; the results were similar [25]. A systematic review of six articles after screening 1,104 entries suggested that sclerotherapy and prolotherapy (PLT) might be effective treatment options for ATP and could be considered safe [26].

George Hackett introduced PLT in the 1950s [27], and it has been used in clinical practice for many years to treat chronic musculoskeletal conditions [28]. Prolotherapy was a safe, nonsurgical regenerative intervention performed under ultrasound guidance by injecting an irritant solution (dextrose 50%) via a 25-gauge needle into the tendon and fenestration of the affected area. Dextrose was considered an ideal proliferant because it was water soluble and could be injected safely into the symptomatic area. The current theory suggests that the injected proliferate mimics the body’s natural healing process by initiating a local inflammatory cascade, which triggers the release of growth factors and collagen deposition [29]. This is accomplished when induced cytokines mediate chemomodulation, leading to the proliferation and strengthening of new connective tissue, joint stability, and reduced symptoms and dysfunction [30,31]. Many randomized controlled trials have demonstrated the effectiveness of injecting 10% to 25% dextrose in treating symptoms associated with damaged ligaments, tendons, cartilage, and joints [32,33,34,35]. A small study comparing PLT, eccentric exercises, and a combination of both showed improvements in symptoms, stiffness, and activity levels [36].

This study aimed to evaluate the effectiveness of treatment for ATP using PTL at Boston Medical Center (Boston, Massachusetts). We reviewed the number of PTLs needed to achieve symptom relief, examined how bone and soft-tissue deformity impact the therapy, reviewed complications, and reviewed the procedures participants sought after failing three PLT sessions.

Materials and Methods

This retrospective study was HIPAA (Health Insurance Portability and Accountability Act of 1996) compliant and received an exemption from the institutional review board of Boston Medical Center. Based on the retrospective study’s status, informed consent was waived. All of the participants were from a hospital-based clinic, located in a safetynet hospital in an urban setting. After the participants were diagnosed as having ATP, they were scheduled for PLT. Musculoskeletal radiologists performed the PLT. Data were collected retrospectively from electronic health records from January 1, 2014, to December 31, 2017.

Participants

We reviewed data from 132 participants with nontraumatic ATP. These participants have ATP from daily activity. We excluded any traumatic cause, history of AT rupture, and tendon pathology. Participants were followed for 12 months; those lost to follow-up were excluded. All of the data were retrieved from electronic health records. All of the statistical calculations and analyses were performed using a spreadsheet program (Excel; Microsoft Corp, Redmond, Washington). This study reviewed the outcomes only and did not compare them with other studies. There was no bias. The podiatric physicians provided information about the participants when the order was written, but the radiologists were not aware of and did not examine the participants.

Data Sources/Measurement

A physical examination was conducted on all of the participants to determine the location and characteristics of their symptoms. Radiographs of standing anterior, lateral, and oblique views of the affected foot were performed for all of the participants. Radiographic results were interpreted by the boardqualified radiologists and reviewed by the podiatric physicians. We followed up with participants for 12 months after the first PLT. After each therapy session, participants were required to wear walking boots for 2 weeks. The podiatric physician saw participants 1 to 2 weeks after the PLT and followed up every 2 to 4 weeks. Participants could have up to three PLTs if needed. The resolution of symptoms was confirmed by examination at a 12-month follow-up visit. The duration of pathology, the number of PLT sessions, and the final data were recorded. Participants who had persistent symptoms after 12 months were advised to proceed with another modality or surgery.

Procedure Protocol

A radiologist reviewed the ultrasound examination and confirmed that the PLT and fenestration procedures were indicated. Risks and benefits were discussed with the participant. Consent was signed. The skin over the posterior heel was prepared and draped in the usual sterile fashion. One percent lidocaine was used for local anesthesia. The AT was examined using ultrasonography to locate the affected area, which would be hyperemic and thickened. Under continuous ultrasound guidance, a 25- gauge needle was advanced into the affected AT. The targeted area of the tendon pathology was gently fenestrated and injected with 1.5 mL of hyperosmolar dextrose solution (dextrose diluted by 50% with 1% lidocaine). Care was taken to avoid direct injection into areas of partially torn tendons. The number of fenestrations depended on the extent of the injury, and the depth was limited to the tendon, avoiding the bone and surrounding neurovascular structures. The needle was removed, and a sterile dressing was applied. Any adverse events were documented. The participant was placed in an immobilization boot for 2 weeks and was advised to avoid strenuous activity. Protected weightbearing after the PLT prevents postprocedure ruptures. After 2 weeks, if appropriate, the participant may begin gentle eccentric stretching exercises.

Results

Descriptive Data

One hundred thirty-two participants, comprising 45 men and 87 women, met the study’s criteria, with a mean age of 55 years (range, 21–80 years). Sixty-four participants (48.5%) reported symptoms on the left side, and 68 (51.5%) on the right side. Seventy participants (53.0%) had HGS, 74 (56.1%) had IAT, 46 (34.8%) had both HGS and IAT, and 35 (26.5%) had MAT. Seventy-three participants (55.3%) had ATP for less than 1 year, and 59 (44.7%) had ATP for more than 1 year (

Table 1. Demographic Characteristics of the Study Participants

).

Primary Outcomes

Overall, in 12 months, 98 participants (74.2%) had resolution of symptoms, of which 58.6% (41 of 70) had HGS, 67.6% (50 of 74) had IAT, 52.2% (24 of 46) had both HGS and IAT, and 91.4% (32 of 35) had MAT. Thirty-four participants (25.8%) still had symptoms after 12 months, of which 29 had HGS, 24 had IAT, 22 had both HGS and IAT, and three had MAT (

Table 2. Outcomes Data

).

Secondary Outcomes

The secondary outcome was to analyze how IAT and HGS impact the therapy. Seventy-one participants (53.8%) experienced symptom improvement with a single treatment. Of these, 33 had HGS, 36 had IAT, 21 had IAT and HGS, and 23 had MAT (Table 2). Sixty-one participants needed more than one treatment: 37 had HGS, 38 had IAT, 25 had both IAT and HGS, and 12 had MAT.

Final Outcomes

Thirty-four participants still had symptoms after 12 months of PLT; 17 sought another treatment, and 17 underwent surgery. Twenty-nine participants with HGS still had symptoms after 12 months; 14 sought another therapy, and 15 had surgery. Twenty-four participants with IAT still had symptoms after 12 months; 10 sought another treatment, and 14 had surgery. Twenty-two participants with HGS and IAT still had symptoms after 12 months; eight sought another therapy, and 14 had surgery. Three participants with MAT still had symptoms after 12 months; one sought another treatment modality, and two had surgery (

Table 3. Final Outcomes Data

). There were no adverse events.

Discussion

The mean age of participants was 55 years for both women and men. Daily activities, not athletics, caused their symptoms. Many treatment modalities had been studied, but most were unavailable for participants at this safety-net institution. Some participants received cortisone injections at our institution or other facilities; they had to wait 3 months before having PLT in this review. Eccentric exercises were shown to be effective in ATP, but the present participants did not participate in this study.

Prolotherapy has been used in various musculoskeletal conditions, including, but not limited to, lateral epicondylitis, rotator cuff tendinopathy, plantar fasciitis, ATP, osteoarthritis, low back pain, sacroiliac joint pain, and temporomandibular joint dysfunction [37]. For the present study, dextrose 50% was used for the irritant, and a 25-gauge needle was used to fenestrate and inject under ultrasound guidance. Participants were placed in a walking boot for immobilization for 2 weeks after the procedure. Using the walking boot was a safety precaution against tendon rupture because of the fenestration procedure. None of the participants had an AT rupture after undergoing the procedures. The participants tolerated the walking boot well. Some of the participants used the walking boot for ATP treatment before undergoing PLT, but the symptoms remained unresolved. Ninety-eight participants (74.2%) resolved their symptoms within 1 year, and 71 (53.8%) needed only one therapy. Often, ATP was classified into midsubstance, IATs, and retrocalcaneal bursitis. We divided the present participants into three groups: IAT for symptoms at the insertion of the AT to the calcaneus, HGS for signs at the posterosuperior aspect of the calcaneus, and MAT for symptoms above these areas. Participants with MAT responded best to PLT; 32 of 35 (91.4%) resolved their pain, with 23 (65.7%) requiring only one treatment. In comparison, 58.6% and 67.6% of participants with HGS and IAT, respectively, reported resolution of their symptoms by 12 months. Most participants had the third PLT, when needed, 6 months after the first PLT. Participants returned for follow-up 6 months after the last therapy. Achilles tendinopathy was found to be a degenerative condition,⁷ and the mechanism for PLT was identified as regenerative [38].

Many studies in the literature did not specify the etiology of ATP. Knowing the specific etiology would help the clinician choose an effective treatment plan. Some participants wanted to avoid surgery, but it might be the best treatment rather than having to fail many other treatments before surgery. The present study showed that half of the participants who failed PLT looked for different therapies, and the other half wanted to have surgery. Many studies need long-term follow-up. Participants with skeletal deformities may derive the most benefit from surgery.

This study was a retrospective analysis subject to the limitations inherent in historical studies, such as the lack of blinding and randomization. Some participants were unable to attend their scheduled therapy sessions. The timing between the second and third therapies could have been more consistent. Monitoring compliance with the use of walking boots after PLT was difficult, and ensuring that participants followed their home treatment was challenging. We had follow-up visits for a maximum of 12 months.

Conclusions

A thorough history and physical examination are essential for managing ATP. All of the participants with chronic symptoms should undergo radiography; magnetic resonance imaging may be necessary to rule out tendon tears. With the combination of early identification and treatment, PLT may alleviate symptoms and prevent the need for surgical intervention. This study showed that PLT had excellent results for ATP without skeletal deformity. No adverse events were reported during the 12-month study. A prospective, comparative, and randomized controlled study with long-term follow-up is needed to determine the efficacy of PLT in ATP.