Description of the condition
The Achilles tendon connects the calf muscles (gastrocnemius, soleus and plantaris) to the heel bone (calcaneus). It transmits muscular forces that effect plantarflexion of the ankle against resistance (such as when standing on tiptoes). It has a fundamental role in walking and locomotion in general. The tendon is composed of a parallel alignment of cross-linked collagen fibres that have a crimped configuration at rest but straighten when under tension (Evans 2000). When the Achilles tendon is subject to greatly increased forces (e.g. sudden increase in intensity of an exercise activity) or repetitive submaximal forces over a prolonged duration, such as in long-distance running, these cross-links begin to fail. This process is followed by a period of remodelling and repair of the damaged tendon (Riley 2008). When there is an imbalance between these two processes, the tendon may begin to exhibit characteristics associated with Achilles tendinopathy, which is sometimes known as 'tendinitis'.
Achilles tendinopathy occurs at either the heel bone (insertion) or mid-portion (3 to 6 cm from the heel bone). The insertion of the Achilles tendon is thought to be predisposed to developing tendinopathy because of the excessive shear and compressive forces that occur at this site. Tendinopathy at the mid-portion (also 'mid-substance') has been attributed to decreased vascularity as the tendon fibres spiral laterally through 90 degrees at this point (Riley 2008). Factors associated with Achilles tendinopathy include biomechanical faults (hyperpronation of the foot), systemic diseases (such as diabetes), smoking, age, activity level and obesity; however, the aetiology is probably multifactorial rather than the result of any one of these considerations (Van Sterkenburg 2011).
Common features of Achilles tendinopathy include pain and stiffness, particularly over the lower portion of the calf. There may also be thickening of the tendon and swelling. Although classically worse in the morning, the pain may be constant or intermittent and aggravated either during or after weight-bearing exercise (Maffulli 2010). Pain on weight bearing in previously active people may cause considerable disruption to activities of daily living, work and sports.
One study in the Netherlands estimated the annual incidence of symptoms attributable to Achilles tendinopathy in the general population at 2.01 per 1000 people (De Jonge 2011). The annual incidence rate for mid-portion Achilles tendinopathy was 1.85 per 1000 people. The annual median age at presentation for mid-portion tendinopathy was 43.4 years; in 34.6% of cases, a specific relationship to sporting activities was noted. However, this study used Dutch general practitioner (GP) practice records and is likely to have underestimated the true incidence as people may have presented to other healthcare practitioners (e.g. physiotherapists) or not presented at all.
Description of the intervention
There is a large array of non-surgical (conservative) interventions available for the management of Achilles tendinopathy (Andres 2008; Kearney 2010; Sussmilch-Leitch 2012). Examples include eccentric exercises, cryotherapy, extracorporeal shockwave therapy, low-level laser therapy, ultrasound, orthotics, splints, topical nitroglycerin, injections and non-steroidal anti-inflammatory drugs (NSAIDS). Our review focuses on injection therapies, of which there are a growing number in use (Coombes 2010).
Injection therapies include a range of options such as corticosteroids, high-volume saline, prolotherapy, autologous blood, platelet-rich plasma, aprotinin, botulinum toxin, sodium hyaluronate, polysulphated glycosaminoglycan and polidocanol (Coombes 2010).
Injection therapies can be guided by real-time ultrasound imaging or unguided; they can be administered in isolation or in combination with any of the above interventions; they can be administered in a single dose or consist of a course, and they can be injected locally into the tendon or targeted at specific sites (such as areas of vascular ingrowth). There is no consensus on many of these factors and the exact intervention is at the discretion of the administering professional (Maffulli 2010).
How the intervention might work
All injection therapies are used to deliver a drug directly to the damaged tendon. In general, these substances are thought to act either pharmacologically (e.g. corticosteroids) or mechanically (e.g. high volume saline to stimulate neovascular growth).
The injection therapies reported in previous systematic reviews (Coombes 2010; DTB 2012) are listed below together with a brief description of their proposed mechanism of action. In broad terms, they have been classified into those targeting the promotion of repair activity through the introduction of substances to act directly on the repair pathway and those promoting repair activity through causing injury or destruction of new vascular ingrowth, or both.
Agents acting directly on the repair pathway
Autologous blood: injected locally to promote repair activity through the administration of growth factors (present in a person's own blood) directly to the site of injury.
Platelet-rich plasma: injected locally to promote repair activity through the administration of concentrated growth factors (present in a person's own blood that has been spun at a high speed to separate out the platelet-rich plasma layer) directly to the injury site.
Aprotinin: injected locally to inhibit collagenase which would otherwise break down collagen and has been found to be increased in tendinopathy.
Polysulphated glycosaminoglycan: injected locally to prevent destruction and facilitate repair through inhibiting metalloproteinase enzyme activity.
Botulinum toxin: injected locally to decrease tensile stress through the tendon and inhibit substance P, which is increased in tendinopathy.
Sodium hyaluronate: injected locally to absorb mechanical stress and provide a protective buffer for tissues.
Corticosteroid: injected locally to down regulate (acting to decrease) inflammation in the affected tendon.
Agents causing injury or disrupting vascular ingrowth to promote repair activity
High volume saline: a saline solution is injected along the surface of Achilles tendon, with or without local anaesthetic. The injection produces a mechanical effect on the new vascular ingrowth associated with tendinopathy, resulting in the new blood vessels stretching and breaking.
Polidocanol: targeted disruption of new vasculature by administration of a scelerosant to precipitate blood vessel fibrosis.
Prolotherapy: hypertonic glucose injected locally to initiate repair activity by causing local tissue trauma.
Injection therapies have a common suite of potential adverse effects, including local infection, bleeding, swelling and tendon rupture. Adverse effects may be the consequence of the injection itself (e.g. local bleeding and weakening of the tendon) or the substance injected.
Why it is important to do this review
Achilles tendinopathy is a common condition, often with significant functional consequences. A review of the evidence from randomised trials of injection therapies to help inform treatment decisions is warranted in the light of the wide range of available treatments, together with an exponential increase in their use (Kaux 2011). A synthesis of the available evidence may also help to direct future research in this area.