Update on non-insertional Achilles tendinopathy

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Update on non-insertional Achilles tendinopathy Aktuelle Entwicklungen in der Behandlung von Achillessehnen-Tendinopathien N. Maffulli a,b,c,d,∗, R. Aicale a,∗∗ a

Department of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, Salerno, Italy Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D’Aragona, 84131 Salerno, Italy c Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London E1 4DG, England, United Kingdom d Keele University, School of Medicine, Institute of Science and Technology in Medicine, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, England, United Kingdom b

Received 28 May 2019; accepted 22 September 2019

KEYWORDS Tendinopathy; Healing; Exercise; Injections; Surgery

∗ ∗∗

Abstract In the past three decades, the incidence of overuse tendinopathy has risen. Tendinopathy affects also middle-aged overweight patients with no history of increased physical activity. Tendinopathy is the result of a chronic failure of healing response. Several conservative therapeutic options have been proposed. The management of tendinopathy is primarily conservative, and many patients respond to such measures. Eccentric exercises and shock wave therapy provide promising excellent clinical results. High-volume injection of normal saline solution, corticosteroids, and local anesthetic can reduce pain and improve long-term function. The use of injectable platelet-rich plasma in and around the tendon is not supported by strong clinical evidence. If clinical conditions do not improve after 6 months of conservative management, surgery is recommended.

Corresponding author. Tel.: +44 20 8567 7553. Pbx: +44 20 8223 8930. Corresponding author. Tel.: +39 345 848 5495. E-Mails: [email protected] (N. Maffulli), [email protected] (R. Aicale).

https://doi.org/10.1016/j.fuspru.2019.09.002

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N. Maffulli, R. Aicale SCHLÜSSELWÖRTER Tendinopathie; Sehnenheilung; Dehnungsübungen; Injektionen; Chirurgie

Zusammenfassung Die Inzidenz von Tendionopathien durch Überlastung ist in den vergangenen drei Dekaden angestiegen. Eine Tendinopathie der Achillessehne wird jedoch auch bei übergewichtigen Patienten ohne erhöhte körperliche Belastung beobachtet. Die Tendinopathie ist das Resultat einer chronischen Störung der physiologischen Heilungsvorgänge. Verschiedene konservative Behandlungsoptionen wurden hierfür vorgeschlagen. Die Therapie der Tendinopathie ist primär konservativ und diese spricht bei vielen Patienten gut an. Exzentrische Dehnungsübungen und extrakorporale Schockwellentherapie führen zu vielversprechenden und exzellenten klinischen Resultaten. High-volume Injektionen von Kochsalzlösung, Corticosteroiden und Lokalanästhetika können zu einer Schmerzreduktion und verbesserter Langzeitfunktion führen. Der Einsatz von injizierbarem plättchenreichen Plasma in und um die Achillessehne ist hingegen nicht mit höhergradiger klinischer Evidenz belegt. Falls die konservativen Maßnahmen nicht innerhalb von 6 Monaten zu einer Besserung des klinischen Befundes führen, wird die chirurgische Therapie empfohlen.

Introduction Achilles tendinopathy (AT) occurs both in athletic and sedentary individuals. The incidence in top level runners has been estimated between 7 and 9% [1], while 30% of patients have a sedentary lifestyle [2]. The etiopathogenesis of AT remains unclear. It is currently considered multifactorial, and interactions between intrinsic and extrinsic factors have been postulated [3]. Changes in training pattern, poor technique, previous injuries, footwear, and environmental factors such as training on hard, slippery or slanting surfaces are extrinsic factors which may predispose athletes to AT [3]. Dysfunction of the gastrocnemius-soleus, age, body weight and height, pes cavus, marked forefoot varus and lateral instability of the ankle have also been recognized as possible risk factors [3]. Fluoroquinolones and corticosteroids have been implicated as risk factors in tendinopathy. Fluoroquinolones cause enhance interleukin-1b-mediated MMP3 release, inhibit tenocyte proliferation, and, as corticosteroids, reduce the collagen and matrix synthesis [4]. The Achilles tendon is not a static and inert tissue, and the tendon extra cellular matrix (ECM) is a dynamic structure constantly remodeled, with rates of turnover depending on loading forces. The ECM is the substrate to which cells adhere, migrate and differentiate. ECM is important for the homeostasis of connective tissue, and its physiological and pathological modifications seem the most important intrinsic factors involved in tendinopathies and tendon ruptures [5]. The turnover of ECM in normal tendon is mediated by matrix metalloproteinases (MMPs) [6], in particular

MMP-1, MMP-2 and MMP-3 [7]. The metalloproteinases are able to denature collagen type I. After tendon rupture, the activity of MMP-1 increases, while a reduction of MMP-2 and MMP-3 is evident [8]. Transglutaminase (TGs) are also implicated in the development of hard tissue, matrix maturation and mineralization [9]. Nine different TGs are present in mammalians. TG2, also known as tissue transglutaminase, is widely distributed within many connective tissues, and it is implicated in organogenesis, tissue repair and tissue stabilization. An animal model showed a reduction of TG2 protein expression in injured supraspinatus tendons [10]. Metabolic diseases, such as diabetes mellitus [11], hypercholesterolemia and obesity, have been recently investigated [12,13]. The relationship between thyroid disorders and joint pain has been suspected since the late 1920s [14], but it has not been systematically investigated. Thyroid hormones (THs) play an essential role in the development and metabolism of many tissues. In fact, thyroxine (T4) is important for both collagen synthesis and extra cellular matrix metabolism. A recent study demonstrates that the TH nuclear receptors are present on tenocytes, and that, in vitro, THs enhance tenocytes growth, and counteract apoptosis in healthy tenocytes isolated from tendon in a dose- and time-dependent manner [15]. Hypothyroidism causes accumulation of glycosaminoglycans (GAGs) in the extracellular matrix, predisposing to tendinopathy and tendon ruptures. Diabetes mellitus is a chronic metabolic disease, and diabetic patients are prone to long-term complications. The pathogenesis of complications is multifactorial, and Advanced Glycation

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Update on non-insertional Achilles tendinopathy End-products (AGEs) play a central role [16]. Protein glycation is a spontaneous reaction which occurs in the presence of glucose and is directly proportional to its blood level. The AGEs can produce further reactions, developing protein crosslinking. Collagen proteins are particularly susceptible to AGE formation, because of their long half-life, and this process may be involved in the physiopathology of tendinopathy [17]. A recent animal study showed that AGEs related collagen crosslinks alter biological and mechanical properties of tendons [18]. Induction of AGEs inhibits sliding between collagen fibers, and this matrix level change lies beneath reduced viscous properties of the tendon tissue. When stretch is applied to a normal tendon, this responds with a collagen fibril sliding more than with fiber stretch [19]. Tendons with formation of AGEs demonstrated a dominant fiber stretch relative to fiber sliding, a nearly complete removal of stress relaxation behavior, significantly altered failure stress and a significantly altered yield behavior [18]. Therefore, the formation of AGEs probably changes the way tendon reacts to loading. Tendons try to compensate this loss of function by increasing collagen fiber stretch, which may have potentially important implications for predisposition to damage during everyday use. Relatively little is known about the role of neuronal regulation in tendinopathy, and the source of pain has not been clarified yet [20]. The presence of pain in tendinopathy not only requires mechanical changes, but also alterations in the way the local cells and the peripheral nerves react to this change. ‘‘Peripheral neuronal phenotype’’ refers to specific characteristics of the peripheral nervous system including nerves, neuronal mediators, and receptors in peripheral tissue. A recent systematic review showed that the peripheral neuronal phenotype is altered in tendinopathy [20], and that the peripheral and central pain processing pathways are important factor in the pathogenesis of painful human tendinopathy, thus, changes in the peripheral neuronal phenotype may be the primary source of pain [20]. There is strong evidence of an upregulation of the glutaminergic system in painful human tendinopathy and weaker, but still suggestive, evidence that changes in the peripheral neuronal phenotype were related to variations in pain symptomatology among patients. Glutamate levels are increased in several painful musculoskeletal disorders [21]. Glutamate is a key metabolite and neurotransmitter involved in the transmission of pain. Glutamate NMDAR1 receptors have been frequently noted in morphologically altered tenocytes

3 in tendon tissue proper and in the peritendinous connective tissue [22]. There is also some evidence for upregulation of the Substance P/CGRP system, which has been implicated in pain generation in both animal models and human disease [20]. The neuropeptides Substance P and CGRP are both vasodilators and both appear to have important roles in tissue healing [23].

Clinical condition Tendinopathy of the mid-portion of the Achilles tendon accounts for 55—65% of all injuries, while in approximately 20—25% of patients an insertional Achilles tendinopathy can be diagnosed. Clinical history and examination are essential for diagnosis. AT is a clinical condition characterized by pain, swelling (diffuse or localized), and impaired performance of the Achilles tendon [24]. Pain is the cardinal symptom of AT, and it occurs at the beginning and a short while after the end of a training session. As the pathological process progresses, pain may occur during the entire exercise session, and, in severe cases, it may interfere with the activities of daily living. Clinical examination is the best diagnostic tool. Location of pain 2—6 cm above the insertion into the calcaneum and pain on palpation are reliable and accurate tests for diagnosis [25]. An evaluation of standing posture, balance and anatomical mal-alignment is usually performed during clinical examination.

Diagnosis Some clinical tests have been described for noninsertional Achilles tendinopathy diagnosis, divided into palpation tests (tendon thickening, crepitus, pain on palpation, the Royal London Hospital (RLH) test, the painful arc sign), and tendon loading tests (pain on passive dorsiflexion, pain on single heel raise, and pain on hopping). The painful arc sign, in which a painful swelling moves with ankle movement, indicates tendinopathy rather than paratendonitis [26]. Less pain of the swelling in ankle dorsiflexion is indicative of tendinopathy with the RLH test [25]. Maffulli et al. studied sensitivity, specificity, reproducibility, and predictive value of palpation of the painful arc sign and of the Royal London Hospital test in 10 patients with Achilles tendinopathy and in 14 asymptomatic subjects, and found no evidence of a difference of the three assessment methods (p > 0.05); when the test were combined, the overall sensitivity was 0.586, and the overall specificity was 0.833 [27].

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Radiography can be used to diagnose associated or incidental bony abnormalities [28], while ultrasound is an effective imaging method, since it correlates well with the histopathologic findings despite being operator-dependent [29]. MRI studies should be performed only if the ultrasound scan remains unclear. MRI provides extensive information on the internal morphology of the tendon and the surrounding structures and is useful in differentiating between peritendinitis and tendinopathy. Areas of mucoid degeneration are shown on MRI as a zone of high signal intensity on T1- and T2-weighted images [30].

The management of Achilles tendinopathy lacks evidence-based support, and patients are at risk of long-term morbidity with unpredictable clinical outcome [28]. The management is primarily conservative, and many patients respond well to conservative measures. Eccentric exercise and shock waves have been proved to be effective for the treatment of AT [31]. However, conservative management is unsuccessful in 24% to 45.5% of patients, and surgery is recommended after 6 months of conservative management [32]. Long standing AT is associated with poor postoperative results, with a greater rate of reoperation before reaching an acceptable outcome [21]. The frequency of surgery increases with patient age, duration of symptoms, and occurrence of tendinopathic changes [33,34]. Both open and mini-invasive surgical techniques have been described for treatment of the mid-portion AT.

Scandinavian authors have reported excellent results in prospective RCTs [40,41]. However, the proportion of good and excellent results in other studies using eccentric exercises is definitely lower [30,32]. Other protocols, such as eccentric—concentric progressing to eccentric (Silbernagel combined) [40] and eccentric—concentric (Stanish and Curwin) [42], have been described. A systematic review showed that combined type exercise have equivalent results to the traditional Alfredson’s protocol [43]. Isotonic, isokinetic, and concentric loading have also been described, but are inferior to the eccentric-type exercises [44,45]. In a prospective randomized controlled study, Rompe et al. [46] showed that eccentric strengthening plus repetitive low-energy shockwave therapy (ESWT) was better than eccentric strengthening alone in terms of Victorian Institute of Sports Assessment — Achilles (VISA-A) scores and pain ratings at four months. The proportion of patients who were ‘completely recovered’ or ‘significantly improved’ on the Likert scale was also significantly better in the combined therapy group (82%) compared with 56% in the strengthening alone group. ESWT where available, should probably be the second line treatment [30]. ESWT works on tissue healing and pain transmission, in particular, regarding the first, they can increase the levels of factors involved in tissue healing, such as TGF-␤1 and IGF-I expression [47] and significantly decrease some interleukins [48] and matrix metalloproteinases (MMPs) on cultured tenocytes [49], while regarding the second, they may change the histological appearance of dorsal root ganglion, modulating both central and peripheral nervous system inducing long-term analgesia [1].

Eccentric exercise

High volume injections

Good results have been reported with eccentric exercises (EE) [35,36], but alone may not work in all patients [32]; however, the mechanism of action is not completely understood [36]. Actually, EE are the most effective conservative treatment for non-insertional Achilles tendinopathy and often are associated with Alfredson’s protocol: the exercises are performed in three sets of 15 repetitions, twice a day for 12 weeks [37]. This regime was demonstrated to be effective in a recent systematic review, and confirmed with a meta-analysis in 2012, which outlined the best pooled data supporting eccentric exercises, with the majority of the studies adopting Alfredson’s protocol [38]. Hailing this as ‘‘probably the greatest single advance in the management of this condition in the past 20 years’’ [39], Alfredson and other

High volume image guided injections (HVIGIs) target the neurovascular bundles growing from the Karger’s fat into the AT. HVIGIs would produce local mechanical effects, causing the neovascularity to stretch, break or occlude, and pain relief could be explained by the destruction of these sensory nerves [2]. Denervation of the Achilles tendon by releasing the paratenon may be the most important part of this procedure. Several substances have been injected in and around tendons, including normal saline, corticosteroids, local anesthetic [50,51]. Platelet rich plasma application did not show the expected benefits in tendinopathic Achilles tendon [52]. The injection is performed under ultrasound guidance to avoid intratendinous injections which can be particularly harmful if corticosteroid is used.

Management of Achilles tendinopathy

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Update on non-insertional Achilles tendinopathy

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Following HVIGI, patients are allowed to walk on the injected leg immediately, but they are strictly advised to refrain from high impact activity for 72 h. After this period, they are instructed to re-start eccentric loading physiotherapy regime twice daily until they stop their sporting career. Good results have been reported with this technique at short term follow-up [53].

Surgery Conservative treatment fails in between one quarter and one third of patients, and surgical intervention is required [34]. For non-insertional AT, surgery has traditionally involved a large incision and excision of all of the pathological tissue, with or without augmentation with a tendon transfer [54]. Open surgery has shown varying success rates between 50% and 100% [55—58] with removal of intratendinous lesions, and good to excellent results [33,59], but the main concern is the risk of complications. A large series of 432 consecutive patients from a specialist center reported an overall complication rate of 11% [60], including skin edge necrosis, wound infection, seroma formation, hematoma, fibrotic reactions, sural nerve injury, tendon rupture and thromboembolic disease. The rate of these complications might decrease with the use of minimally invasive techniques [61] which strip the paratenon from the tendon, either directly [62] or indirectly with high-volume fluid injection [51], and shown good initial results in relieving the symptoms [61,63]. This surgical treatment would appear to be a useful intermediate step between failed conservative treatment and formal open surgery [61]. Another technique involves multiple percutaneous longitudinal tenotomies, which produce good results, with the advantage of being able to perform the procedure under local anesthesia in an outpatient setting [64,65]. Open surgery Under local regional or general anesthesia, the patient is placed prone with the ankles clear of the operating table. The incision is made on the medial side of the tendon to avoid injury to the sural nerve. In patients with evidence of coexisting paratendinopathy, the scarred and thickened tissue is excised. Based on preoperative imaging studies, the tendon is incised sharply in line with the tendon fiber bundles. The tendinopathic tissue can be identified as it generally has lost its shiny appearance and it frequently contains disorganized fiber bundles that have more of a ‘‘crabmeat’’ appearance. This tissue is sharply excised (Fig. 1). The

Fig. 1. The tendinopathic tissue must be identified and sharply excised.

Fig. 2. A mosquito clamp was inserted through the proximal incisions to free the peritendinous adhesions.

remaining gap can be repaired using a side-to-side repair, but we leave it unsutured. If significant loss of tendon tissue occurs during the débridement, a tendon augmentation or transfer could be considered. Successful results have been reported with this surgical procedure. A systematic review showed successful results in over 70% of cases [66], but these relatively high success rate are not always observed in clinical practice. Possible complications of this surgical procedure are wound healing problems, infection, sural nerve injury, rupture of the AT, and deep vein thrombosis. Minimally invasive stripping Surgery is performed under local anesthesia and with the patient prone, as a day case procedure. Four small (0.5 cm) longitudinal skin incisions, in line with the Achilles tendon, are. Two proximal incisions are produced just medial and lateral to the origin of the tendon, and two distal ones medial and lateral to the calcaneal insertion of the tendon. A mosquito clamp is inserted through the proximal incisions (Fig. 2), to free the peritendinous adhesions. A Number 1 unmounted Ethibond (Ethicon, Somerville, NJ) suture is doubled up and passed transversely through the two proximal incisions. (Fig. 3) and then retrieved distally in a X fashion. In practice, a suture retriever is inserted

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Fig. 5. The retriever was inserted from the distal medial stab wound to the proximal lateral stab wound.

Fig. 3. Ethibond was first passed transversely through the two proximal stab wounds and then retrieved distally in a X fashion.

Fig. 4. A suture retriever was inserted from the distal lateral stab wound to the proximal medial.

from the distal lateral stab wound to the proximal medial (Fig. 4), and then the unmounted Ethibond is brought out of the distal lateral stab wound, the retriever is inserted from the distal medial stab wound to the proximal lateral stab wound (Fig. 5), to repeat the process. The unmounted Ethibond is retrieved from the distal medial and lateral stab wound, a gentle see-saw motion is applied (similar to using a Gigli saw around bone), and then the Ethibond is gently advanced over the interface between the Achilles tendon and the Kager fat. The tendon is thus stripped and freed from the Kager’s triangle fatty tissue. The stab wounds can be left open [67], or closed in a standard fashion. Forty-seven consecutive athletic patients (36 males and 11 females), with a mean age of 35 years (SD 9.5, range 25—58 years) did not respond to nonoperative management and underwent minimally invasive stripping for midportion Achilles

tendinopathy. All the patients were followed postoperatively in outpatient clinics for at least 24 months (mean 40.5, SD 7.4, range 24—52 months). The average VISA-A score improved from 53.8 (SD 7.9; range 41—69) preoperatively, to 85.3 (SD 6.7; range 72—94) at the last follow up (p < 0.001; Student’s T-test). Calf circumference and strength was similar between affected and non-affected legs, before and after surgery. Six of the 47 patients (12.8%) did not return to playing sports (three patients played soccer, two were runners, and one played squash). They were all young male patients (mean age 31.8; SD 6.8; range 25—42 years). The remaining 41 patients returned to sports after an average of 3.5 months (SD 0.6; range 2—5 months). Six of these 41 patients stated that they returned to a lower level of sports activity compared to before their tendinopathy problem had started. Percutaneous longitudinal tenotomies The patient lies prone on the operating table with the feet protruding beyond the edge, and the ankles resting on a sandbag. The area of maximum swelling and/or tenderness marked. A surgical scalpel blade (Swann-Morton, England) is inserted parallel to the long axis of the tendon fibers in the marked area(s) with the cutting edge pointing cranially. After reversing the position of the blade, a full passive ankle plantar-flexion movement is produced. The procedure is repeated 2 cm medial and proximally, medial and distally, lateral and proximally and lateral and distally to the site of the first stab wound. The five wounds are closed with steristrips (3M United Kingdom PLC, Bracknell, Berkshire, England), dressed with cotton swabs, and a few layers of cotton wool and a crepe bandage are applied [68]. A total of 39 runners were reviewed at an average follow-up of 17 years (range, 15—22 years) and at the final follow-up, the maximum calf circumference and the strength in the operated leg

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Update on non-insertional Achilles tendinopathy were not significantly different than those measured preoperatively, but they were significantly lower than those on the contralateral side. All patients returned to their preinjury occupation. In particular, 20 patients were still active in middleand long-distance running, with an average current level of sport and function that was 60% ± 13% compared with the onset before of symptoms. Thirty of 39 patients (77%) reported good or excellent outcomes on the basis of the Boyden assessment. At US assessment, the tendon was generally thicker than the contralateral asymptomatic tendon (average, 7.0 vs. 8.7 mm, respectively). No significant difference ha be found when compared patients with good or excellent Boyden results versus those with fair or poor outcomes. The mean VISA-A score was 78.5, with no significant difference between patients with and without paratendinopathy. All of the patients who did not return to running or who gave up sports activities had signs of paratendinopathy [68].

Conclusion The incidence of Achilles tendinopathy has risen in the past three decades. It mainly arises from overuse, and it is the result of a chronic failure of healing response. The management of the acute Achilles tendinopathy at presentation is primarily conservative using eccentric exercises and shock waves therapy. High-volume injection of normal saline solution, corticosteroids and local anesthetic can be used after failure of three mouths of conservative management [50,51]. If clinical conditions do not improve after 6 months of conservative management, surgery is recommended.

Conflict of interest Not declared.

References [1] Rompe JD, Furia JP, Maffulli N. Mid-portion Achilles tendinopathy — current options for treatment. Disabil Rehabil 2008;30:1666—76, http://dx.doi. org/10.1080/09638280701785825. [2] Ames PRJ, Longo UG, Denaro V, Maffulli N. Achilles tendon problems: not just an orthopaedic issue. Disabil Rehabil 2008;30:1646—50, http://dx. doi.org/10.1080/09638280701785882. [3] Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. J R Soc Med 2004;97:472—6, http://dx. doi.org/10.1258/jrsm.97.10.472.

7 [4] Parmar C, Meda KP. Achilles tendon rupture associated with combination therapy of levofloxacin and steroid in four patients and a review of the literature. Foot Ankle Int 2007;28:1287—9, http://dx. doi.org/10.3113/FAI.2007.1287. [5] Modesti A, Oliva F. All is around ECM of tendons!? Muscles Ligaments Tendons J 2013;3:1, http://dx.doi.org/10.11138/mltj/2013.3.1.001. [6] Dalton S, Cawston TE, Riley GP, Bayley IJ, Hazleman BL. Human shoulder tendon biopsy samples in organ culture produce procollagenase and tissue inhibitor of metalloproteinases. Ann Rheum Dis 1995;54:571—7. [7] Choi H-R, Kondo S, Hirose K, Ishiguro N, Hasegawa Y, Iwata H. Expression and enzymatic activity of MMP-2 during healing process of the acute supraspinatus tendon tear in rabbits. J Orthop Res Off Publ Orthop Res Soc 2002;20:927—33, http://dx.doi.org/10.1016/S0736-0266(02)00016-5. [8] Riley GP, Curry V, DeGroot J, van El B, Verzijl N, Hazleman BL, et al. Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol J Int Soc Matrix Biol 2002;21:185—95. [9] Tarantino U, Oliva F, Taurisano G, Orlandi A, Pietroni V, Candi E, et al. FXIIIA and TGF-beta over-expression produces normal musculo-skeletal phenotype in TG2−/− mice. Amino Acids 2009;36:679—84, http://dx.doi.org/10.1007/s00726-008-0133-7. [10] Oliva F, Zocchi L, Codispoti A, Candi E, Celi M, Melino G, et al. Transglutaminases expression in human supraspinatus tendon ruptures and in mouse tendons. Biochem Biophys Res Commun 2009;379:887—91, http://dx.doi.org/ 10.1016/j.bbrc.2008.12.188. [11] de Oliveira RR, Lemos A, de Castro Silveira PV, da Silva RJ, de Moraes SRA. Alterations of tendons in patients with diabetes mellitus: a systematic review. Diabet Med J Br Diabet Assoc 2011;28:886—95, http://dx.doi.org/10.1111/j.1464-5491.2010.03197. x. [12] Oliva F, Via AG, Maffulli N. Physiopathology of intratendinous calcific deposition. BMC Med 2012;10:95, http://dx.doi.org/10.1186/1741-7015-10-95. [13] Oliva F, Berardi AC, Misiti S, Maffulli N. Thyroid hormones and tendon: current views and future perspectives. Concise review. Muscles Ligaments Tendons J 2013;3:201—3. [14] Duncan WS. The relationship of hyperthyroidism to joint conditions. J Am Med Assoc 1928;91:1779—82, http://dx.doi.org/10.1001/jama.1928.02700230019006. [15] Oliva F, Berardi AC, Misiti S, Verga Falzacappa C, Falzacappa CV, Iacone A, et al. Thyroid hormones enhance growth and counteract apoptosis in human tenocytes isolated from rotator cuff tendons. Cell Death Dis 2013;4:e705, http://dx.doi. org/10.1038/cddis.2013.229. [16] Ahmed N. Advanced glycation endproducts—–role in pathology of diabetic complications. Diabetes

Please cite this article in press as: Maffulli N, Aicale R. Update on non-insertional Achilles tendinopathy. FussSprungg (2019), https://doi.org/10.1016/j.fuspru.2019.09.002

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N. Maffulli, R. Aicale

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26] [27]

[28]

[29]

Res Clin Pract 2005;67:3—21, http://dx.doi. org/10.1016/j.diabres.2004.09.004. Reigle KL, Di Lullo G, Turner KR, Last JA, Chervoneva I, Birk DE, et al. Non-enzymatic glycation of type I collagen diminishes collagenproteoglycan binding and weakens cell adhesion. J Cell Biochem 2008;104:1684—98, http://dx.doi. org/10.1002/jcb.21735. Li Y, Fessel G, Georgiadis M, Snedeker JG. Advanced glycation end-products diminish tendon collagen fiber sliding. Matrix Biol J Int Soc Matrix Biol 2013;32:169—77, http://dx.doi. org/10.1016/j.matbio.2013.01.003. Screen HRC. Investigating load relaxation mechanics in tendon. J Mech Behav Biomed Mater 2008;1:51—8, http://dx.doi.org/10.1016/j.jmbbm.2007.03.002. Dean BJF, Franklin SL, Carr AJ. The peripheral neuronal phenotype is important in the pathogenesis of painful human tendinopathy: a systematic review. Clin Orthop 2013;471:3036—46, http://dx.doi.org/10.1007/s11999-013-3010-y. Kreiner F, Galbo H. Elevated muscle interstitial levels of pain-inducing substances in symptomatic muscles in patients with polymyalgia rheumatica. Pain 2011;152:1127—32, http://dx.doi.org/10.1016/j.pain.2011.01.032. Schizas N, Weiss R, Lian O, Frihagen F, Bahr R, Ackermann PW. Glutamate receptors in tendinopathic patients. J Orthop Res Off Publ Orthop Res Soc 2012;30:1447—52, http://dx.doi.org/10.1002/jor.22094. Carlsson O, Schizas N, Li J, Ackermann PW, Substance P. injections enhance tissue proliferation and regulate sensory nerve ingrowth in rat tendon repair. Scand J Med Sci Sports 2011;21:562—9, http://dx.doi.org/10.1111/j.1600-0838.2009.01080. x. Maffulli N, Khan KM, Puddu G. Overuse tendon conditions: time to change a confusing terminology. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc 1998;14:840—3. Hutchison A-M, Evans R, Bodger O, Pallister I, Topliss C, Williams P, et al. What is the best clinical test for Achilles tendinopathy? Foot Ankle Surg Off J Eur Soc Foot Ankle Surg 2013;19:112—7, http://dx.doi.org/10.1016/j.fas.2012.12.006. Williams JG. Achilles tendon lesions in sport. Sports Med Auckl NZ 1993;16:216—20. Maffulli N, Kenward MG, Testa V, Capasso G, Regine R, King JB. Clinical diagnosis of Achilles tendinopathy with tendinosis. Clin J Sport Med Off J Can Acad Sport Med 2003;13:11—5. Maffulli N, Testa V, Capasso G, Oliva F, Sullo A, Benazzo F, et al. Surgery for chronic Achilles tendinopathy yields worse results in nonathletic patients. Clin J Sport Med Off J Can Acad Sport Med 2006;16:123—8. Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med 2003;22:675—92.

[30] Rompe JD, Nafe B, Furia JP, Maffulli N. Eccentric loading, shock-wave treatment, or a wait-andsee policy for tendinopathy of the main body of tendo Achillis: a randomized controlled trial. Am J Sports Med 2007;35:374—83, http://dx.doi. org/10.1177/0363546506295940. [31] Frairia R, Berta L. Biological effects of extracorporeal shock waves on fibroblasts. A review. Muscles Ligaments Tendons J 2011;1:138—47. [32] Sayana MK, Maffulli N. Eccentric calf muscle training in non-athletic patients with Achilles tendinopathy. J Sci Med Sport 2007;10:52—8, http://dx. doi.org/10.1016/j.jsams.2006.05.008. [33] Maffulli N, Binfield PM, Moore D, King JB. Surgical decompression of chronic central core lesions of the Achilles tendon. Am J Sports Med 1999;27:747—52, http://dx.doi.org/10.1177/03635465990270061101. [34] Paavola M, Kannus P, Paakkala T, Pasanen M, Järvinen M. Long-term prognosis of patients with achilles tendinopathy. An observational 8-year follow-up study. Am J Sports Med 2000;28:634—42. [35] Weinreb JH, Sheth C, Apostolakos J, McCarthy M-B, Barden B, Cote MP, et al. Tendon structure, disease, and imaging. Muscles Ligaments Tendons J 2014;4:66—73. [36] Maffulli N, Via AG, Oliva F. Chronic Achilles tendon disorders: tendinopathy and chronic rupture. Clin Sports Med 2015;34:607—24, http://dx.doi. org/10.1016/j.csm.2015.06.010. [37] Alfredson H, Pietilä T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. Am J Sports Med 1998;26:360—6, http://dx.doi. org/10.1177/03635465980260030301. [38] Sussmilch-Leitch SP, Collins NJ, Bialocerkowski AE, Warden SJ, Crossley KM. Physical therapies for Achilles tendinopathy: systematic review and meta-analysis. J Foot Ankle Res 2012;5:15, http://dx.doi.org/10.1186/1757-1146-5-15. [39] Rees JD, Maffulli N, Cook J. Management of tendinopathy. Am J Sports Med 2009;37:1855—67, http://dx.doi.org/10.1177/0363546508324283. [40] Silbernagel KG, Thomeé R, Thomeé P, Karlsson J. Eccentric overload training for patients with chronic Achilles tendon pain—–a randomised controlled study with reliability testing of the evaluation methods. Scand J Med Sci Sports 2001;11:197—206. [41] Roos EM, Engström M, Lagerquist A, Söderberg B. Clinical improvement after 6 weeks of eccentric exercise in patients with mid-portion Achilles tendinopathy — a randomized trial with 1-year follow-up. Scand J Med Sci Sports 2004;14:286—95, http://dx.doi.org/10.1111/j.1600-0838.2004.378.x. [42] Stanish WD, Rubinovich RM, Curwin S. Eccentric exercise in chronic tendinitis. Clin Orthop 1986:65—8. [43] Malliaras P, Barton CJ, Reeves ND, Langberg H. Achilles and patellar tendinopathy loading programmes: a systematic review comparing clinical outcomes and identifying potential mechanisms for

Please cite this article in press as: Maffulli N, Aicale R. Update on non-insertional Achilles tendinopathy. FussSprungg (2019), https://doi.org/10.1016/j.fuspru.2019.09.002

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ARTICLE IN PRESS

Update on non-insertional Achilles tendinopathy

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

effectiveness. Sports Med Auckl NZ 2013;43:267—86, http://dx.doi.org/10.1007/s40279-013-0019-z. Niesen-Vertommen SL, Taunton JE, Clement DB, Mosher RE. The effect of eccentric versus concentric exercise in the management of achilles tendonitis. Clin J Sport Med 1992;2:109. Mafi N, Lorentzon R, Alfredson H. Superior shortterm results with eccentric calf muscle training compared to concentric training in a randomized prospective multicenter study on patients with chronic Achilles tendinosis. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 2001;9:42—7, http://dx.doi.org/10.1007/s001670000148. Rompe JD, Furia J, Maffulli N. Eccentric loading versus eccentric loading plus shock-wave treatment for midportion achilles tendinopathy: a randomized controlled trial. Am J Sports Med 2009;37:463—70, http://dx.doi.org/10.1177/0363546508326983. Chen Y-J, Wang C-J, Yang KD, Kuo Y-R, Huang H-C, Huang Y-T, et al. Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression. J Orthop Res Off Publ Orthop Res Soc 2004;22:854—61, http://dx.doi. org/10.1016/j.orthres.2003.10.013. Rees JD, Wilson AM, Wolman RL. Current concepts in the management of tendon disorders. Rheumatol Oxf Engl 2006;45:508—21, http://dx.doi.org/10.1093/rheumatology/kel046. Han SH, Lee JW, Guyton GP, Parks BG, Courneya J-P, Schon LC. J. Leonard Goldner Award 2008. Effect of extracorporeal shock wave therapy on cultured tenocytes. Foot Ankle Int 2009;30:93—8, http://dx.doi.org/10.3113/FAI-2009-0093. Loppini M, Maffulli N. Conservative management of tendinopathy: an evidence-based approach. Muscles Ligaments Tendons J 2011;1:134—7. Chan O, O’Dowd D, Padhiar N, Morrissey D, King J, Jalan R, et al. High volume image guided injections in chronic Achilles tendinopathy. Disabil Rehabil 2008;30:1697—708, http://dx.doi.org/ 10.1080/09638280701788225. de Vos RJ, Weir A, van Schie HTM, Bierma-Zeinstra SMA, Verhaar JAN, Weinans H, et al. Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA 2010;303:144—9, http://dx.doi.org/10.1001/jama.2009.1986. Maffulli N, Spiezia F, Longo UG, Denaro V, Maffulli GD. High volume image guided injections for the management of chronic tendinopathy of the main body of the Achilles tendon. Phys Ther Sport Off J Assoc Chart Physiother Sports Med 2013;14:163—7, http://dx.doi.org/10.1016/j.ptsp.2012.07.002. Maffulli N, Aicale R, Tarantino D. Autograft reconstruction for chronic Achilles tendon: techniques in foot & ankle surgery. Tech Foot Ankle Surg 2017;16:117—23, http://dx.doi.org/10.1097/BTF.0000000000000154. Lohrer H, David S, Nauck T. Surgical treatment for achilles tendinopathy — a systematic

9

[56]

[57]

[58] [59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

review. BMC Musculoskelet Disord 2016;17:207, http://dx.doi.org/10.1186/s12891-016-1061-4. Kvist H, Kvist M. The operative treatment of chronic calcaneal paratenonitis. J Bone Joint Surg Br 1980;62:353—7. Schepsis AA, Leach RE. Surgical management of Achilles tendinitis. Am J Sports Med 1987;15:308—15, http://dx.doi. org/10.1177/036354658701500403. Snook GA. Achilles tendon tenosynovitis in longdistance runners. Med Sci Sports 1972;4:155—8. Paavola M, Kannus P, Orava S, Pasanen M, Järvinen M. Surgical treatment for chronic Achilles tendinopathy: a prospective seven month follow up study. Br J Sports Med 2002;36:178—82. Paavola M, Orava S, Leppilahti J, Kannus P, Järvinen M. Chronic Achilles tendon overuse injury: complications after surgical treatment. An analysis of 432 consecutive patients. Am J Sports Med 2000;28:77—82, http://dx.doi. org/10.1177/03635465000280012501. Maffulli N, Oliva F, Maffulli GD, Giai Via A, Gougoulias N. Minimally invasive Achilles tendon stripping for the management of tendinopathy of the main body of the Achilles tendon. J Foot Ankle Surg Off Publ Am Coll Foot Ankle Surg 2017;56:938—42, http://dx.doi.org/10.1053/j.jfas.2017.05.019. Longo UG, Ramamurthy C, Denaro V, Maffulli N. Minimally invasive stripping for chronic Achilles tendinopathy. Disabil Rehabil 2008;30:1709—13, http://dx.doi.org/10.1080/09638280701786922. Alfredson H. Ultrasound and Doppler-guided mini-surgery to treat midportion Achilles tendinosis: results of a large material and a randomised study comparing two scraping techniques. Br J Sports Med 2011;45:407—10, http://dx.doi.org/10.1136/bjsm.2010.081216. Testa V, Capasso G, Benazzo F, Maffulli N. Management of Achilles tendinopathy by ultrasound-guided percutaneous tenotomy. Med Sci Sports Exerc 2002;34:573—80. Maffulli N, Testa V, Capasso G, Bifulco G, Binfield PM. Results of percutaneous longitudinal tenotomy for Achilles tendinopathy in middle- and longdistance runners. Am J Sports Med 1997;25:835—40, http://dx.doi.org/10.1177/036354659702500618. Tallon C, Coleman BD, Khan KM, Maffulli N. Outcome of surgery for chronic Achilles tendinopathy. A critical review. Am J Sports Med 2001;29:315—20, http://dx.doi.org/10.1177/03635465010290031101. Maffulli N, Pintore E, Petricciuolo F. Arthroscopy wounds: to suture or not to suture. Acta Orthop Belg 1991;57:154—6. Maffulli N, Oliva F, Testa V, Capasso G, Del Buono A. Multiple percutaneous longitudinal tenotomies for chronic Achilles tendinopathy in runners: a long-term study. Am J Sports Med 2013;41:2151—7, http://dx.doi.org/10.1177/0363546513494356.

Please cite this article in press as: Maffulli N, Aicale R. Update on non-insertional Achilles tendinopathy. FussSprungg (2019), https://doi.org/10.1016/j.fuspru.2019.09.002