University of Groningen
The influence of load on tendons and tendinopathy
Maciel Rabello, Lucas
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Maciel Rabello, L. (2019). The influence of load on tendons and tendinopathy: Studying Achilles and
patellar tendons using UTC. Rijksuniversiteit Groningen.
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Chapter 10
152 | Chapter 10
Load can cause either positive or negative adaptations in tendons. Positive adaptations will be observed when there is a balance between load and recovery, which will maintain tendon homeostasis and improve its load capacity.1 When this balance is chronically or repetitively disturbed it results in maladaptation.2 This negative response can cause pain and functional impairment, symptoms typically observed in patients diagnosed with tendinopathy. Interestingly, load can also be used to reduce tendon-related symptoms in tendinopathy. What happens at the tendon structure level is not completely elucidated yet. The general aim of this thesis is to gain knowledge about the influence of load (in sports and rehabilitation) on Achilles and patellar tendon structure.
The first aim of this thesis was to investigate the use and role of ultrasound tissue characterization (UTC) to characterise and quantify tendon structure in research and clinical practice. A systematic review was conducted that included all papers describing studies that used UTC to assess tendon structure (Chapter 2). The use of UTC can be divided in three main domains: predicting and diagnosing pathology, and monitoring changes in tendon structure. The systematic review showed that regarding prediction, a higher amount of disorganised structure seems to be related to an increase in the risk of developing patellar tendinopathy (PT). Regarding diagnosis, UTC might provide additional information (e.g. assessing the involvement of the plantaris tendon in patients diagnosed with Achilles tendinopathy [AT]). The systematic review also showed that UTC might play an important role in monitoring the effect of load or treatment on tendon structure. The results of the reliability study in Chapter 3 showed that UTC is a reliable imaging tool to quantify and characterise patellar tendon structure.
The second aim of this thesis was to investigate the influence of load on Achilles and patellar tendons without tendinopathy. The studies included in Chapters 4 and 5 investigated the acute influence of a single bout of exercise on Achilles tendon structure. The influence of low and moderate load was investigated in a cross-sectional study with subjects running on a treadmill under two weight-bearing conditions (20% of body weight and 100% of body weight) for 20 minutes (Chapter 4). The influence of high load was investigated in a cohort study assessing the effect of running a marathon (Chapter 5). We observed that low-to-moderate load did not cause changes in tendon structure 2 and 7 days post-exercise. However, high load (running the marathon) caused a significant increase in amount of aligned fibrillar structure 7 days post-exercise.
Despite the fact that changes in tendon structure are influenced by the amount of load performed, only a limited number of studies have quantified accumulated load and investigated the association with changes in tendon structure. An observational study (Chapter 6) therefore investigated the association between load during preseason and changes in patellar tendon structure in elite volleyball players. It was observed that an increase in load was related to a decrease in intact and aligned tendon bundles and an increase in less integer and waving tendon bundles.
The third and final aim of this thesis was to investigate the association between changes in tendon structure and changes in clinical outcome after conservative treatment (mainly based on load management and loading exercise) of patients diagnosed with AT or PT. First, the tendon structure of the asymptomatic and symptomatic sides of patients diagnosed with unilateral AT or PT was investigated (Chapter 7). The results showed that both sides were compromised, compared to controls. Chapters 8 and 9 aimed to investigate
the association between changes in clinical outcomes and changes in tendon structure after treatment. The systematic review showed a lack of association between clinical and conventional imaging outcomes after therapeutic loading exercise at short-term follow-up (Chapter 8). However, at long-term follow-follow-up there is a moderate association. This association might be affected by factors like tendinopathy location, exercise modality performed, and follow-up period. A limited number of studies investigated the association between clinical and imaging examination using UTC. Hence we performed a prospective study investigating the association between function and pain (measured with the Victorian Institute of Sport Assessment [VISA] questionnaire) and tendon structure (measured with UTC) after conservative treatment (Chapter 9). At short-term follow-up an improvement in pain and function was associated with a decrease of less integer and waving tendon bundles. Additionally, when patients were analysed individually a higher percentage of agreement was observed between less pain and improved function and an increase of intact and aligned tendon bundles, decrease of fibrillar tissue (AT) and a less amorphous matrix with loose fibrils, cells or fluid (PT).
This General Discussion will present the main findings of the studies included in this thesis from a broader perspective. The first part of the discussion focuses on the effect of load on the Achilles and/or patellar tendon structure. The second part discusses the changes in tendon structure compared to those in clinical outcomes, before and/or after conservative treatment of patients diagnosed with AT or PT. Recommendations for future research are provided and practical implications for coaches, athletes, physiotherapists and physicians are described. The final conclusions of this thesis will be presented taking into consideration the strengths and limitations of the studies.
Influence of load on tendons
Studying the influence of load on tendons is important for anybody who is engaged in physical activity, including athletes but also patients with a chronic disease.
Recreational and elite athletes expose their tendons to repetitive load in order to participate in sports or improve their performance. One of the risks of training and sports participation is the development of a musculoskeletal injury related to overload, like tendinopathy.8 In both Achilles and patellar tendinopathy – typical sports-related tendinopathies – load is the most important risk factor.8–10 For example, Visnes et al. (2013) demonstrated that in young volleyball players a higher volume of training increased the risk of developing patellar tendinopathy.11 Thus understanding the association between load performed and changes in tendon structure is essential for the prevention of tendinopathy.12
Over the past two decades being physically active has been increasingly recommended to promote health and to prevent and manage chronic diseases.3 But physical activity can also be part of the treatment of chronic conditions like diabetes and chronic pain.5,6 In such cases exercise is medicine, so individuals are encouraged to exercise on a regular basis.6 Besides the evidence-based benefits for health, being physically active can also have its side effects.7 Suffering from a (tendon) injury can hamper participation in exercise/exercise programmes, and significantly impacts patients’ quality of life. A physically active lifestyle General discussion | 153
is essential, especially for patients with diabetes, obesity and hypercholesterolemia, and yet these patients have an increased risk for tendon problems. More basic insight into the association between load and tendon changes is of the utmost importance towards being able to develop personalised rehabilitation programmes.
In the continuum model proposed by Cook & Purdam, load is the primary stimulus that moves the tendon forward and back on the continuum, especially in the early stages.13 However, knowledge about the amount of load (intensity, frequency and volume) that is necessary to cause positive or negative tendon adaptation needs to be improved. To prescribe personalised exercise programmes for patients with chronic disease or to design optimal training programmes for athletes, more insight into the interaction between load and tendon structure is needed.
It was not until recently that a quantitative imaging tool, UTC, was introduced to study the influence of load on tendon structure. Most of these studies focused on volume of exercise and provided limited information on intensity, type of activity or whether the activity level had changed.14–18 In addition to the information on load performed, knowledge about how the tendon structure recovers after load is also essential to prevent overuse. Chapters 4-6 of this thesis therefore investigated the influence of these specific load parameters and the recovery period on the tendon structure of individuals without tendinopathy.
The findings of this thesis suggest that the response of the tendon structure depends on load frequency and volume performed. A single bout of exercise caused no significant changes in the Achilles tendon structure (Chapter 4), but when the frequency of exercise increased (Chapters 5) significant changes in tendon structure were observed. In Chapter 6, besides the different activity performed, both frequency and volume increased and an association between an increase in load and changes in tendon structure was observed. However, looking at load intensity it was shown in our studies that neither light or moderate nor high intensities (performed isolated) caused significant changes in tendon structure. This can be explained by the theory that the response of the tendon to the load not only depends on load intensity, frequency and volume but also on an individual’s tendon load capacity.19,20 Tendon capacity is the ability of the tissue to tolerate load, meaning that it indicates whether the individual is either able or unable to complete a task or participate in physical activity.21 To build tendon capacity progressive overload (‘disturb’ of the tendon homeostasis) with sufficient amount of recovery is required. That means that positive tendon adaptation can be expected when the load performed exceeds the tendon capacity and a sufficient amount of recovery is given.
The findings of this thesis are in line with the theory proposed in the continuum model. Our results suggest that there is an initial reaction of the tendon to the load performed which occurs before the reactive symptomatic stage of the continuum model. If the load performed is followed by an appropriate amount of recovery, the tendon will show a positive adaptation. But an imbalance between load and recovery will probably cause a tendon reaction that is followed by pain, which fits with the reactive stage of the model. As described previously, the findings of this thesis suggests that the load necessary to cause a positive or negative tendon adaptation will depend on the tendon load capacity. For example, the same external load (e.g. number of jumps) performed by elite volleyball players over seven weeks (Chapter 6) could cause a negative reaction in the
tendons of novice volleyball players, as their load capacity is lower. Another example is load performed by a population with a chronic disease, like diabetes. The load capacity in this population is decreased,23 so even an increase in leisurely physical activity (walking, hiking, dancing) above their capacity increases the risk of developing tendinopathy. To make things even more complex, the adaptation of tendon structure to the load performed is not just influenced by load and load capacity: other factors influence load capacity, tendon structure and the association between load, load capacity and tendon structure. This has already been recognised by the authors of the continuum model, who called these the individual factors. Following general sports injury prevention models, these individual factors can be divided into four main categories: historical, biomechanical, environmental and psychological. It is known that some of these factors, like aging (historical factor)24 and biomechanics (physical factor),25,26 can affect the influence of load on tendon structure. For example, previous studies identified that different biomechanical strategies, like trunk position during landing26 and ankle dorsiflexion,25 might increase or decrease overload in tendons. Other factors, like psychological ones, urge further investigations to identify their influence on the capacity of the tendon to support the load; a recent systematic review identified just four studies in the field of tendinopathy.27 It is important to observe that not all these factors are adaptable. The physical factors and some of the environmental factors refer to characteristics of the individual or to certain characteristics of the sport that cannot be modified. For example, environmental factors like a hard training surface can affect the influence of load on the tendon and increase the risk of tendinopathy.28 For prevention purposes, the modifiable factors are important. Professionals can use different interventions to modify the influence of these factors on tendon adaptation. Hence clinical examination that includes, for example, an interview, questionnaires and a physical examination, is necessary to gain information not only about load performed but also about the presence of those factors. Re-examinations over the period should also be performed since load, individual factors and tendon capacity are interlinked; any change in one component affect the others.29 Future longitudinal large-scale cohort studies are needed and should consider those factors when investigating the influence of load on tendon structure.
The association between imaging and clinical outcomes in patients diagnosed with tendinopathy
Load, which plays an important role in tendon adaptation, is also a key factor in the treatment of tendinopathy. Amongst others, a recent study demonstrated again the importance of treatment of tendinopathy based on load management.30 Loading exercises can reduce pain, improve function and increase tendon capacity by improving tendon structure and/or tendon properties. However, the association between changes in clinical outcomes (pain and function, for example) and changes in tendon structure is not completely understood.31 The studies included in Chapters 8 and 9 of this thesis aimed to investigate that association after a rehabilitation programme based on loading exercise in patients diagnosed with AT or PT.
156 | Chapter 10
The complex association between clinical and imaging outcomes might begin even before the symptoms arise. This complexity is detailed in the ‘iceberg theory’.32,33 The tendon structure can be compromised without presence of symptoms – asymptomatic tendons – for a long period. This was observed in Chapter 7 of this thesis, which showed that the asymptomatic side of patients with unilateral AT or PT is also compromised compared to controls. These findings corroborate previous studies that used conventional imaging tools.34,35 When tendons become symptomatic, the structure of the tendon may have already changed into one of the more advanced stages of the continuum model, with a limited capacity of reversibility.13 Corroborating previous findings – the systematic review included in Chapter 8 – showed that, at short-term follow-up, an association is lacking between changes in clinical outcome and changes in tendon structure (measured with conventional imaging tools) after therapeutic loading exercises.
The association between clinical and imaging outcomes might be different when investigated at long-term follow-up, which was indeed observed in the systematic review included in Chapter 8 (stronger association at long-term follow-up compared to short-term follow-up). These findings might be explained by the duration of the exercise programme performed by the patients. The treatment frequently lasts 12 weeks, but afterwards patients can continue with the intention to further increase load capacity. The findings can also be influenced by the fact that after 12 weeks of treatment, patients improved clinically and were able to return to their physical activity, which can also influence tendon structure. This is in line with a previous study showing that exercises performed over a longer period result in more beneficial adaptations to the tendon structure than shorter periods of exercises.36 The majority of the studies investigating the effect of treatment on tendon structure have focused only on the short-term effect, just directly after the end of 12 weeks of treatment. A reason for this might be that conducting research that includes long-term follow-up is more expensive and time-consuming. However, our findings suggest that future studies should investigate the effect of therapeutic loading exercises also at long-term follow-up and use new quantitative imaging techniques like UTC.
Even with the newest imaging techniques, it is not clear yet if tendon structure normalises after treatment based on therapeutic loading exercise. According to some authors, the treatment should be focused on the peripheral aligned fibrillar matrix portion of the tendon (echo types I and II) that is located around the central degenerative area (echo types III and IV).19 It is suggested that the loading exercises-based treatment should be used to increase the load capacity of the aligned fibrillar matrix portion, which in this way can adapt to and withstand the load during tendon-loading activities. However, literature confirming this theory is limited and the findings of this thesis are not in line with this hypothesis. The study described in Chapter 9 using UTC to investigate tendon structure is the first to demonstrate that about 50% of patients who improved clinically above the minimal detectable change (MDC) also had a reduced percentage of echo-degenerative area. The findings show that even the disorganised structure can be influenced by load at short-term follow-up. These subtle findings were probably not observed in Chapter 8 because the majority of the studies included in the review used conventional imaging tools, which might not be able to detect these small changes. The results from Chapter 9 suggest that other factors like aging and previous history of tendinopathy might also influence changes in tendon structure.
As stated in the previous section, load is considered the primary stimulus that influences tendon structure and, consequently, also the association with clinical outcomes. Tendinopathy however is considered to have a multifactorial aetiology. As observed in tendons without tendinopathy, different factors are involved in the association between load and tendon structure, but how these factors exactly influence the tendon structure of subjects with tendinopathy is not clear yet. For example, in patients with diabetes it is known that because of an increased amount of crosslinks tendons become more vulnerable.37 There is only limited knowledge as to why these tendons react differently than non-diabetic tendons.
In recent years researchers and clinicians have debated the influence of psychological factors on patient rehabilitation.27,38,39 But how can psychological factors influence tendon structure? Patients with fear of pain, lack of motivation, little social support and/ or low self-efficacy, for example, show less adherence to an exercise-based treatment programme; they perform less exercise with less intensity.38 Low frequency combined with low intensity does not activate the trigger responsible for causing changes in tendon structure. On the other hand, those who are highly motivated and experience high pressure from their social environment (coach, team, family) continue to play despite pain, causing negative changes in tendon structure. Further investigations need to be conducted to increase knowledge about the role of psychological factors in the treatment of tendinopathy.27
The complex interaction between load and other factors and its influence on tendon structure stress that rehabilitation should be individualised. At the moment of choosing the most appropriate intervention, the characteristics of the exercise (intensity, frequency and duration) as well as the individual factors (historical, physical and psychological) should be considered. To improve knowledge about the importance of these aspects, future studies should systematically document individual characteristics of the subjects. More individualised rehabilitation programmes can be developed using this information.
Due to the previously reported lack of association between clinical and imaging outcomes, nowadays researchers and clinicians are still discussing the relevance of investigating tendon structure after treatment to determine the next stage of treatment and, in case of athletes, the safest and most successful moment to full return to play. The limited evidence supporting use of imaging examination has resulted in a tendency to minimise the attention for tendon structure during and after rehabilitation. However, the results of this thesis, combined with those of some previous studies, suggest that tendon structure should be considered during the examination as it might be related to tendon capacity.30 Monitoring load and tendon structure are important to determine whether tendon structure is reacting in a positive or negative way. An adequate (personalised) balance between load and load capacity will result in positive adaptation, while overload conditions for a prolonged period can enlarge the degenerative area and even increase the risk of tendinopathy.
Recommendations for future research
More research is needed that investigates the influence of load on Achilles and patellar tendon structure with and without tendinopathy. Specific recommendations for future research on this topic are provided below:
• The majority of studies investigating the influence of load on tendon structure arelimited by the amount of subjects recruited, which implies that those results should beinterpreted with caution. Future research should investigate the association between load and tendon structure in prospective studies with a large sample size. Such studies should be characterised by a clear and uniform description of terminology, relevant patient characteristics and stage of the disease (following the ISTS2018 Groningen consensus statements).
• To improve personalised rehabilitation, longitudinal cohort studies should be conducted to investigate the effect of the same load performed by patients with different characteristics – for example, investigating the influence of load on the tendon structure of subjects with vs without previous history of tendinopathy, or investigating the influence of load on tendons at different stages of pathology (according to the continuum model).13 • There is a limited number of studies investigating the influence of load on tendon structure at long-term follow-up in subjects without tendinopathy. Hence more research is needed to determine the association between the initial reaction of the tendon and adaptation or maladaptation at long-term follow-up.
• The influence of load on the tendon structure of patients with chronic diseases who start physical activity as part of their treatment should be investigated in future studies. • In patients diagnosed with tendinopathy, most of the studies that investigated the association between changes in clinical outcomes and imaging outcomes (using new imaging modalities) did this at short-term follow-up. The review included in Chapter 8 of this thesis showed that imaging outcomes using conventional imaging tools presented a stronger association with clinical outcomes at long-term follow-up. More studies are needed to investigate the association between clinical and imaging outcomes measured with new imaging tools at short-term but especially at long-term follow-up.
• Future studies should focus on investigating the influence of other factors, in addition to load, on the tendon structure of patients diagnosed with tendinopathy who follow treatment based on loading exercises.
Practical implications of this thesis
Considering the findings of this thesis, the following implications for practice can be given which can be used by coaches, clinicians and those involved in the prevention and/ or management of Achilles and/or patellar tendinopathy:
• Practitioners should be aware that the amount of load performed can influence tendon structure, but this depends on tendon load capacity, which is influenced by several factors. Careful monitoring of external and internal load may provide better insight into the training process and guide intervention strategies.
• In patients with unilateral tendinopathy the asymptomatic side should not be used as reference. It is nonetheless advised to scan both sides, as asymptomatic tendons showing structural abnormalities are at a high risk of developing symptoms.
• Imaging examination, including conventional and new imaging tools (e.g. UTC) can be used to investigate the influence of conservative treatment based on loading exercises. Clinicians should however be aware that the follow-up period might influence the results and consequently the interpretation.
• Clinicians are advised to perform imaging examination to investigate the changes in tendon structure at short-term follow-up, as there seems to be no association with clinical outcomes.
• Imaging examination can be used to monitor changes in tendon structure after treatment, providing additional information that support clinicians in decisions regarding the rehabilitation programme and/or return to play.
160 | Chapter 10
Limitations
When interpreting the findings of this thesis some limitations should be taken into account. One of the limitations of this thesis is the small sample size in Chapters 3-8 and 9, which may influence the generalizability of the results. The limited number of subjects included was due to specific characteristics of the population. For example, in Chapter 6, male elite volleyball players were recruited. Sample sizes of studies in elite athletes are in most studies small, since the total group of available elite athletes is small because of their unique skills. Despite the fact that research in elite athletes is challenging because of diminished availability of the players, but also because of difficulties with planning of research activities at a suitable time in their training program while taking into account the matches/events and travel schedule of the team, we were able to monitor training load of individual players on a daily basis and assessed tendon structure bi-weekly, with less than 2% missing data. Such a complete dataset did not exist in literature yet and provided novel insight in the relation between training load and tendon adaptations.
In Chapter 9, a unique group of patients from a tendinopathy clinic was recruited. To the best of our knowledge this is still one of the larger groups of outpatient tendinopathy patients in which UTC has been used to detect changes over time. However, since these patients were part of usual care, some selection bias might have occurred as treatment outcome may have influenced the follow-up rates. For example, patients that were not satisfied with the treatment outcome were more likely to return to the follow-up visit compared to those patients who were satisfied. Additionally, due to the study design, it was not fully possible to control for some potential confounders, like concurrent treatment and/or concurrent sport participation. On the other hand, the study design has the advantage of including patients in research that are representative for the group of patients that visits outpatient clinics around the world (ecological validity). Moreover, monitoring these patients in daily care is a first step towards the development of a (inter)national database of patients diagnosed with tendinopathy. Such a database would take away some of the limitations of the studies described in this thesis and also of those published in international literature thus far.
Another limitation of this thesis is that the methodology of UTC changed over time. This limits comparability between studies. Since it is a relatively new imaging technique, over the last years new insights regarding the methodology of scanning and analyzing the images were released, including for example, patient position and the use of different window sizes (9, 17 or 25). For that reason, a different window size was used in Chapter 4 compared to the other studies. Furthermore, patients were positioned in a different position (stand) in Chapter 5 compared to the other studies (prone). Although methodological differences between studies may limit comparability, we applied the same procedures within each study and assessed individual changes over time. With the development of a new tool, methodological modifications are inevitable, but should be considered when comparing studies in the future. To address this limitation and to facilitate comparison between the results of the studies and its applicability in the clinical care, we provided a suggestion for standardization of the UTC methods (scanning and analyzing) based on previous studies and our expertise. The statistical analyses of the UTC studies thus far were done without taking into account that the four (echo types I-IV) or two (echo types I+II, III+IV) UTC categories are dependent. More advanced and complex statistical analyses might be needed to address this.
Overall, this thesis describes the influence of load in the Achilles and patellar tendons in a unique population using a new quantitative imaging technique. Despite the aforementioned limitations this thesis contributes to a better understanding of how tendons (with and without tendinopathy) react to load and treatment in both the sport and clinical setting.
Conclusion
In general, this thesis showed that load, performed as either physical exercise or as treatment, can influence the structure of the Achilles and patellar tendons of individuals with and without tendinopathy. In individuals without tendinopathy, short-term tendon reactions were observed after loading. Future research will have to reveal if these changes in tendon structure result in an adaptation or maladaptation in the long term, considering the individual load capacity. In patients diagnosed with Achilles or patellar tendinopathy an association between clinical and imaging examination was found at long-term but not at short-term follow-up. The UTC imaging tool can be used in tendons both with and without tendinopathy to investigate the influence of load on tendon structure, since subtle changes can be reliably observed. However, a more standardised scanning and imaging analysis method is recommended to facilitate comparison of scientific results and to strengthen the use of this tool in clinical practice.
The results of this thesis will help athletes, patients, coaches, physical trainers and clinicians in the personalised prescription of their training or rehabilitation programmes, which will ultimately improve prevention and management of tendinopathy.
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