Foot and Ankle Injections in Athletes

Abstract

Context:

Injections are commonly used by health care practitioners to treat foot and ankle injuries in athletes despite ongoing questions regarding efficacy and safety.

Evidence Acquisition:

An extensive literature review was performed through MEDLINE, Google Scholar, and EBSCOhost from database inception to 2021. Keywords searched were injections, athletes, sports, foot and ankle, corticosteroids, platelet-rich plasma, and placental tissue. Search results included articles written in the English language and encompassed reviews, case series, empirical studies, and basic science articles.

Study Design:

Clinical review.

Level of Evidence:

Level 4.

Results:

Corticosteroids, platelet-rich plasma/autologous blood, anesthetic, and placental tissue injections are commonly used in the treatment of foot and ankle injuries. Primary indications for injections in athletes include plantar fasciitis, Achilles tendinosis, isolated syndesmotic injury, and ankle impingement with varying clinical results.

Conclusions:

Despite promising results from limited case series and comparative studies, the data for safety and efficacy of injections for foot and ankle injuries in athletes remain inconclusive.

While anesthetic injections have routinely been performed in athletes over the past several decades, newer treatment modalities have recently been introduced to address specific foot and ankle injuries. These modalities include platelet-rich plasma (PRP), autologous blood, placental tissue, and injectable non-steroidal anti-inflammatory drugs (NSAIDs). Despite their popularity, injections in the lower extremities have lacked high-level clinical studies assessing their effectiveness in athletes. In addition, injections about the foot and ankle have historically faced controversy regarding their efficacy and safety profile. ⁸² There are those that argue that athletes with a painful injury should be prohibited from participating in competitive sport rather than playing though an injury with the assistance of the analgesic effects given from an injection. Overall, it has become increasingly difficult for health care professionals to make evidence-based treatment plans because of the lack of high-quality literature and a continually changing options of available treatments.

While injection indications for some foot and ankle pathologies are well accepted, the clinical benefit for others is less understood. The purpose of this review is to evaluate the current literature regarding different types of injections in the foot and ankle with a focus on management of common pathologies seen in athletes including plantar fasciitis, Achilles tendinopathy, syndesmotic injury, and ankle impingement.

Types of Injections

Corticosteroids

Corticosteroid injections have historically been a mainstay of treatment in athletes to address common foot and ankle injuries. ³² Minor muscle trauma and soft tissue strain while playing sports often lead to secondary inflammation that can cause a myriad of symptoms in the lower extremities. Corticosteroids may reduce the inflammatory response by decreasing essential inflammatory contributors including prostaglandins, leukotrienes, and prostacyclin. ⁸ Additionally, corticosteroids disrupt neutrophilic response and reduce swelling by limiting the permeability of the local vasculature. Steroids, being fat soluble, are able to pass through the cell membrane and affect cellular response at the transcription level. ⁴⁷ However, the inflammatory cascade is an essential component of normal healing, and inhibition of this cascade can theoretically suppress the natural healing process.

Corticosteroids are well known for their systemic side effects and potential complications associated with overuse or inappropriate placement of the medication. Systemic side effects include, but are not limited to, insulin resistance, weight gain, osteoporosis, and immunodeficiency. ⁸ By delivering corticosteroids locally, many of these side effects can be minimized. However, local complications can still exist and include skin hypopigmentation, fat atrophy, superficial and deep infection, soft tissue irritation, and tendon and/or ligament rupture. ⁶⁴

Local corticosteroid injections can cause significant systemic effects in soft tissue, whereas intraarticular injections tend to have fewer generalized effects due to containment within the joint capsule. ¹⁷ Corticosteroid injections are often recommended after other nonsurgical treatments have failed such as stretching, bracing, NSAIDs, and physical therapy. In the athlete, corticosteroid injections can be used acutely to decrease local soft tissue inflammation with the goal of an earlier return to play. ²³ Corticosteroid injections should not be given if there is any concern for local soft tissue infection such as cellulitis as this could spread and worsen the infection. Injections should also not be given immediately before participation in competitive sports because of concern of artificially masking an injury that could be exacerbated. ⁵²

There are several different corticosteroid formulations currently available for multiple soft tissue targets. These formulations vary in their dosage, solubility, and other characteristics. ³⁰ In general, a corticosteroid’s solubility is inversely related to its duration of activity and clinical effect. ¹⁴ Soluble corticosteroids such as dexamethasone have a rapid onset but short duration of effects with more systemic side effects. ³⁰ Betamethasone acetate is commonly used in intraarticular and peritendinous injections because of its particulate nature and lower solubility allowing for a greater clinical benefit over an extended period. ¹⁴ Adding local anesthetics such as lidocaine or bupivacaine to formulations can be useful to assist with diagnosis, provide immediate analgesia, and aid in soft tissue distribution because of increased injectable volume. ⁶³ Unfortunately, no consensus exists regarding the formulation, dosage, number of, and frequency of injections that are needed for the treatment of many soft tissue pathologies in the athlete.^21,63

PRP and Autologous Blood

PRP is a derivative of autologous whole blood and consists of a high concentration of platelets along with multiple growth factors including, but not limited to, platelet-derived growth factor, fibroblast growth factor, insulin-like growth factors 1 and 2, and vascular endothelial growth factor. ²⁹ The growth factors and cytokines released by platelets have multiple effects on stem cell proliferation, cell signaling, and angiogenesis. ³⁵ The high concentration of these growth factors contributes to the normal healing process of soft tissue repair and are the foundation for the theoretical benefits of PRP. ⁶⁰

There is a significant variety of different formulations of PRP that currently exist in the market with varying concentrations of platelets, leukocytes, cytokines, and growth factors. ²⁷ Additionally, there are significant differences in the preparation and production of PRP. ⁸⁴ Typically, blood is taken from a patient, centrifuged to remove erythrocytes, and then injected locally into or around the injured tissue. PRP is available in either leukocyte-rich or leukocyte-poor formulas that have been described to have unique benefits. Leukocyte-rich PRP formulas are preferred for treatment of tendinopathies such as Achilles tendinopathy^10,86 due to a support of the natural inflammatory response required for healing. ⁷¹ Over the past 2 decades, indications for the use of PRP therapy have grown consistently to include the majority of orthopaedic conditions seen in practice. ⁴⁶

Because of its portrayal in the media as an advanced treatment modality for athletes, PRP has gained particular popularity among “weekend warriors” and high-level athletes despite limited evidence concerning its efficacy for various musculoskeletal injuries. ⁶⁹ According to Kantrowitz et al, ⁴⁶ patient-driven utilization of PRP therapy was a key factor as to whether team physicians decided to use PRP as a treatment modality. Despite its consistent popularity, PRP therapy still faces many unanswered questions. There is still an ongoing debate regarding the ideal composition of PRP, the appropriate number of injections, and the optimal timing to deliver PRP therapy. ⁵⁷

Placental Tissue

Placental tissue–based products have been used for the management of chronic wounds and burns because of their regenerative capabilities. ²⁶ They can consist of amniotic membrane, umbilical cord, umbilical cord blood, or chorionic membrane tissue that is acquired from donor mothers at the time of delivery. ³⁶ Additionally, varying methods of harvesting, sterilization, preparation, and storage make standardization difficult. ⁴² However, modern methods of sterilization and storage have resulted in increased use for a variety of musculoskeletal injuries. ⁴⁵ Fetal tissue and placental-based tissue have a uniquely high concentration of growth factors, matrix components, and cytokines that stimulate tissue healing while simultaneously decreasing inflammation and scar formation. ⁵⁴ Through the use of hyaluronic acid, amniotic membrane tissue may inhibit transforming growth factor-β, thus reducing scar formation. ⁵⁶ Amniotic membrane–derived stem cells also benefit from a relative lack of ethical concerns regarding harvest since they are obtained from the placenta of volunteers.

Amniotic stem cells can be divided into amniotic epithelial cells and amniotic mesenchymal stromal cells. ⁴⁹ The former is maternally derived, while the latter is derived from the embryonic mesoderm. Both differentiate into cells from all 3 germ layers. ⁴¹ Therefore, they can both differentiate into mesodermal derived myocytes, osteocytes, and chondrocytes. ⁸³ As a result, interest has developed into using placental tissue–based products as a treatment modality for common foot and ankle ailments including plantar fasciitis and Achilles tendinopathy. There is no current evidence that any of the commercially available placental tissues contain live, active cells.

Ketorolac and Analgesics

Ketorolac is a commonly used injectable NSAID indicated for acute short-term analgesia that can be delivered intramuscularly. ⁸¹ Ketorolac works rapidly, with pain relief seen within 10 minutes with peak effects occurring at approximately 45 minutes after injection. ¹¹ Ketorolac’s anti-inflammatory effect is due to nonselective inhibition of both the cyclooxygenase-1 and cyclooxygenase-2 pathways. Through inhibition of these pathways, NSAIDs alter neutrophil recruitment, reduce lysosomal enzyme release, and inhibit thromboxane resulting in a reduced inflammatory response.^12,52 Prostaglandins play a key role in sensitizing afferent pain receptors, and the analgesic effects of NSAIDs have been attributed to their reduction in prostaglandin levels. ⁶⁸

Despite their popularity, NSAIDs have a number of well-known adverse effects. Through a combination of local irritation to the gastrointestinal mucosa, reduction of protective prostaglandins, and inhibition of platelet aggregation, gastrointestinal side effects range from nausea, indigestion, and gastrointestinal reflux to more severe gastrointestinal bleeding. ²⁴ Reduction in prostaglandins also modulates afferent kidney arteriole dilation and renal perfusion resulting in chronic renal disease. ²⁵ The inhibitory effect of extended NSAID use on prostaglandin levels has been shown to slow fracture healing in human subjects and therefore use of serial ketorolac injections has also been discouraged in the treatment of acute fractures.^5,13,31 Cardiovascular toxicity is a well-known adverse effect of NSAIDs but is rarely seen in healthy young athletes. ²⁵

The severity of potential gastrointestinal side effects is likely lowered when NSAIDs are locally injected. ¹¹ However, ketorolac still retains many of its negative systemic effects. Bleeding times in healthy patients increase with even a single ketorolac dose.^22,77 The clinical significance of bleeding time increase is unclear but considered a risk among contact athletes. In a survey by the National Olympic Committee Team during the Rio Olympic Games, team physicians preferred injectable NSAIDs over opioids and analgesics as the treatment of choice for pain relief among athletes. ³⁴ In a 2012 survey of 1100 sport medicine physicians, 49% of respondents used ketorolac injections in high-level athletes. ⁷⁵ However, pregame ketorolac in the National Football League (NFL) has drastically decreased since the NFL Physician Society Task Force recommended limited use.^58,76

Local analgesics slow down axonal transmission though the blockade of sodium channels. ⁷⁹ Analgesic injections are commonly used in athletes for the alleviation of acute pain and to confirm diagnoses such as tendon and/or ligament tears. Local analgesics are also commonly mixed with corticosteroids to manage the acute pain from the injection and increasing the distribution area of the corticosteroid. ⁶³ Concerns for athletes playing through injuries using these injections and therefore causing greater bodily harm have caused some governing bodies such as the International Rugby Board to ban the use of analgesic injections.^65-67

Botulinum Toxin A

Botulinum toxin A is neurotoxin made by the bacterium Clostridium botulinum, which inhibits the release of acetylcholine at the neuromuscular junction resulting in muscle paralysis and relaxation. ²⁰ It was first used in humans for the treatment of strabismus, but its use has since expanded to a myriad of disorders caused by muscle overactivation and dystonia. ²⁸ Botulinum toxin A has an analgesic effect through its inhibition of glutamate, substance P, and calcitonin-gene-related peptide release. ⁶ These neurotransmitters are active in the nociceptive neural pathway. Because of its combined effects as a muscle paralytic and an analgesic, botulinum toxin A may be indicated for soft tissue conditions such as plantar fasciitis, Achilles tendinitis, and muscle strains.

Indications

Plantar Fasciitis

Plantar fasciitis is the most common cause of heel pain in adults and often presents gradually on the medial side. It is typically self-limited but can persist with a chronic remitting course. Though poorly understood, it is likely a degenerative process resulting from repetitive trauma rather than a chronic inflammatory process. ⁴⁴ Athletes, especially those in running sports, have high rates of plantar fasciitis ⁷⁸ as a result of functional biomechanical deficits and overuse. ⁴⁸

Conservative management for plantar fasciitis typically begins with physical therapy, eccentric stretching, NSAIDs, and orthotics. The American College of Foot and Ankle Surgeons included corticosteroid injections as part of their treatment guidelines for plantar heel pain in 2010. ⁸⁰ A recent meta-analysis showed that corticosteroid injections resulted in better pain relief than noninvasive options in the first 3 months of treatment. ¹⁵

Though not as effective or fast at decreasing pain compared with corticosteroids, autologous blood injections appear safe as a second-line treatment option when corticosteroid injections fail. ⁵³ In a randomized control study ⁵³ with 64 patients, intralesional autologous blood injection was efficacious in lowering pain on visual analog scale (VAS). However, these results were not significantly different than the control corticosteroid group.

Similarly, when compared with corticosteroid injections, PRP therapy for plantar fasciitis showed no significant difference in VAS, American Orthopaedic Foot and Ankle Society (AOFAS) scores, or plantar fascial thickness seen on magnetic resonance imaging. ⁴³ However, both groups did show clinical improvement overall. ⁴³ Other studies^2,4 have shown no statistically significant difference in clinical benefit between PRP therapy and corticosteroid injections. However, PRP may have a longer duration of action than corticosteroids injections.^2,4

Amniotic injections for plantar fasciitis appear safe and clinically beneficial. ⁸⁷ In a study ⁸⁵ evaluating patients with plantar fasciitis nonresponsive to noninvasive therapy, a single ultrasound-guided human amniotic membrane and amniotic fluid injection lowered VAS pain levels as early as 4 weeks after injection and minimal pain at 12 weeks. Forty-five patients who received human amniotic/chorionic membrane injections showed significant improvements in both AOFAS and Wong-Baker FACES scores compared with saline controls at 8-week follow-up. ⁸⁷ A follow-up double-blind randomized study ³⁷ with 14 patients compared cryopreserved human amniotic injection with corticosteroids and found no difference in foot pain or VAS while having no patient-reported adverse events.

Botulinum toxin A injections into the medial heel may be an effective treatment for persistent plantar fasciitis. ³ A randomized control study ⁷³ reported significantly lower VAS scores at 12-month follow-up in patients who received botulinum toxin A injections compared with corticosteroids. Recently, botulinum toxin A injection into the medial gastrocnemius resulted in decreased VAS, increased AOFAS scores, and improved dorsiflexion when compared with a saline injection alone. ¹ Athletic performance did not decrease.

Achilles Tendinosis

Tendinosis is a noninflammatory degenerative process resulting from microtrauma, normal aging, and tendinitis. ³⁸ Injectable therapies for Achilles tendinosis include corticosteroid, PRP, and autologous blood injections.

A systematic review comparing injectable treatments for noninsertional Achilles tendinosis resulted in inconclusive evidence supporting the use of these treatments. ³³ Injectable therapies had only mild-to-moderate pain reduction and function, similar to placebo. ³³ Given the lack of significant improvements with injections, percutaneous debridement of the tendon may be the best invasive approach to promote healing. ³³

Studies^18,19 comparing PRP therapy with saline placebo in the management of Achilles tendonitis have failed to show a statistically significant differences in clinical outcomes. A recent randomized control study ⁹ of 60 patients with chronic Achilles tendinosis found that PRP in combination with eccentric exercise training resulted in reduced pain, improved activity level, and reduced tendon thickness. However, these findings were also seen in patients who received high-volume injections of steroids, saline, or local anesthetic with no differences in outcomes between groups. ⁹ A single PRP injection for chronic noninsertional Achilles tendinopathy significantly improved outcomes in Victorian Institute of Sport Assessment–Achilles scores at average of 50 months. ⁷⁹ In 30 patients with chronic Achilles tendinosis treated with PRP, AOFAS scores increased at 24 months posttreatment, with resolution of pretreatment imaging abnormalities in the majority of patients. ⁶¹

Historically, corticosteroids injections for Achilles tendinosis have been contraindicated because of the risk of Achilles tendon rupture.^55,59 A retrospective analysis ⁷ of 342 Achilles tendons treated with corticosteroids found partial Achilles tears were twice as likely. However, the increased rate of tendon rupture may be highest for intratendinous injections; paratendinous or bursa injections may minimize this risk. ⁷⁰

Syndesmotic Injuries

Syndesmotic injuries are common in impact sports. ³⁹ Isolated syndesmotic injuries can be managed conservatively with rest, elevation, and anti-inflammatory medication, and a short immobilization period in a removable walking boot. ⁴⁰ In a randomized control study ⁵¹ in elite athletes with syndesmotic injury, ultrasound-guided PRP injections resulted in a shorter return to play and less long-term residual pain. A cohort study ⁷⁴ evaluating rugby players treated with a single dose of PRP therapy following syndesmotic injury resulted in a significantly faster return to play when compared with a control group. In addition, the PRP group also had higher functional outcomes with no adverse events.

Ankle Impingement

Ankle impingement syndrome is common in football, soccer, track and field, and ballet. ⁵⁰

Anesthetic injections have been used to confirm the diagnosis. ¹⁶ In a series of 18 athletes, ankle impingement symptoms were improved in 84% of patients treated with fluoroscopic-guided corticosteroid injections. ⁶² Sonographic-guided corticosteroid injections may also improve ankle impingement in athletes. ⁷²

Conclusion

In plantar fasciitis, corticosteroid injections remain a first-line treatment. Corticosteroid steroid injections for Achilles tendinosis should be avoided because of the potential risk of tendon rupture. PRP therapy may be an effective adjunct to conservative management of syndesmotic injuries helping athletes return to sport in a shorter period of time. Anesthetic and corticosteroids may be useful with ankle impingement in the acute setting until definitive intervention.

PRP therapy, placental tissue, autologous blood, and botulinum toxin A injections for treatment of foot and ankle injuries in athletes require further research and randomized controlled trials to justify clinical use.