Musculoskeletal Injuries in Ultra-Endurance Running: A Scoping Review

Ultra-endurance running (UER) has seen an important increase in participation over the last few decades. Long hours of UER can lead to excessive stress on the body, resulting in musculoskeletal injuries (MSKI). UER is not a uniform sport and events can differ considerably in distance (over 42.195 km), time (e.g., events over 6 h) and multi-day or multi-stage events on various surfaces (e.g., track, on-road, off-road). The aims of this scoping review were therefore: (1) to examine the current evidence of MSKI, providing a synthesis of the most common MSKI by anatomical region and specific diagnosis; (2) categorize MSKI by type of UER activity (competition: time-limited; multi-stage; continuous UER events and training); (3) describe knowledge gaps in the literature and provide advice on potential further research. Our electronic literature search (PubMed, SPORTDiscus, Web of Science) identified a total of 13 studies (9 in competition, and 4 in training). Anatomical site, diagnosis and rate of injuries differ between competition and training as well as between different UER types. MSKI are observed in 18% of multi-stage events (0.7–1.8 injuries/runner and 7.2 injuries/1000 h). Most MSKI involve the lower leg (35.0%), ankle (16.8%), knee (13.1%) and foot (12.6%), with main diagnosis of medial tibial stress syndrome (30.1%) and patella femoral pain syndrome (PFPS; 7.2%). Single, continuous UER events differ between a 1005 km road race with almost all of the injuries due to overuse, with the main anatomical site of the knee (31%), ankle (28%) and lower leg (14%) and main diagnosis of PFPS (15.6%), compared to a 65 km trail race, with 32.8% of MSKI, mainly on the foot [plantar fasciitis (28.6%)], ankle [sprain (28.6%)] and knee. Timed-UER events (injury rate of 2.1 injuries/athlete) observed most injuries on the ankle (36%) and knee (19%), with the main diagnosis of tendinitis of the foot dorsiflexors (30%). Injuries during training most commonly affect, the back (42%), and knee (40%) and bone stress injuries (22%). Main diagnoses include ankle sprain (18%), iliotibial band injury (16%) and Achilles tendinopathy (11%). Future considerations include examining MSKI in different UER events, environments and surfaces, and on larger study populations. Establishing risk factors, examining sex differences and using a standard reporting system of MSKI in UER are also important.


INTRODUCTION
Humans are well suited to running long distances, having evolved as persistence hunters, capable of covering great distances in pursuit of prey (Scheer, 2019). Ultra-endurance running (UER) tests the limits of the human body and has become increasingly popular over the last few decades, with an exponential increase that has slowed slightly since ∼2016 (Scheer, 2019). This increase is in large part due to an increase in female and master athlete (athletes ages > 35 years) participation (Eichenberger et al., 2012;Knechtle et al., 2012;Zingg et al., 2013;Scheer, 2019). In addition, there has been a similar increase in participation of youth athletes (<19 years of age), although numbers are much smaller compared to adults (Scheer and Hoffman, 2019;Scheer et al., 2020b,c). In 2019 alone, over 669,000 runners finished an UER event and there were over 7000 UER events hosted around the world (DUV, 2019). The exception of course, was 2020, with a significant reduction in UER participation and events, due to the global COVID-19 pandemic (Scheer et al., 2021).
Ultra-endurance running is not a uniform sport but can be defined as a broad category with different types of running activities, such as running events by distance (e.g., any distance in excess of the standard marathon distance of 42.195 km), time (timed-UER, e.g., any events over 6 h) and multi day/multistage events (distance or timed events over several days or stages) (Scheer et al., 2020a). UER events can be held on various surfaces (e.g., track, on-road, off-road) (Scheer et al., 2020a) and in extreme challenging environments, putting additional strain on the human body (e.g., extreme cold, altitude, mountain, desert, heat and jungle) (Knoth et al., 2012;da Fonseca-Engelhardt et al., 2013;Gill et al., 2015;Scheer and Murray, 2015;Dawadi et al., 2020;Suter et al., 2020). The most popular race distances are those of 50 km, 100 km, and 100 miles (Cejka et al., 2014;Scheer, 2019;Knechtle et al., 2020), but can also include distances in excess of 1000 km (Fallon, 1996;Schütz et al., 2012;Scheer et al., 2020a), whereas time-limited events often include 6, 12, or 24 h events, with some lasting several days (Hutson, 1984;Bishop and Fallon, 1999;Scheer et al., 2020a). Multi day/multi-stage events are often held in extreme environments, and athletes often need to carry their provisions, resulting in additional weight while running as a further challenge (Krabak et al., 2011;Knoth et al., 2012;Dawadi et al., 2020;Scheer et al., 2020a).
Musculoskeletal injuries in running have been defined as "running-related (training or competition) musculoskeletal pain in the lower limbs that causes a restriction on or stoppage of running (distance, speed, duration, or training) for at least 7 days or 3 consecutive scheduled training sessions, or that requires the runner to consult a physician or other health professional" (Yamato et al., 2015b), however, definitions of MSKI in UER vary across studies, which make comparisons difficult. Some defined MSKI as a disability resulting in a medical encounter (Krabak et al., 2011;Vernillo et al., 2016), or affecting performance (Bishop and Fallon, 1999). The severity of an injury had been described as severe, if it did not improve with rest (Hutson, 1984), major, resulting in race withdrawal, or minor, when the runner was able to continue the race (Krabak et al., 2011;Vernillo et al., 2016).
It is well established that physiological demands within this broader spectrum of UER may vary, depending on event type (e.g., distance, surface, and elevation changes) (Davies and Thompson, 1986;Bassett and Howley, 2000;Millet and Millet, 2012;Scheer et al., 2020a). For example, the fractional utilization of VO 2 max in a 24 h race is between ∼40-50% (Millet et al., 2011), whereas shorter races of 6 h duration can be run at ∼70% of VO 2 max (Giovanelli et al., 2017). If these higher running intensities in UER increase the risk of MSKI is currently unknown. Similarly, UER with large elevation changes, especially prolonged downhill running sections, place particular demand on the musculature with prolonged eccentric muscle action, leading to increased release of muscle enzymes (creatine kinase) and muscle damage (Dewolf et al., 2016;Giandolini et al., 2017;Vernillo et al., 2017). Such variability makes it likely that MSKI and injury rates will also be affected by the different types of UER events, like timed-events, multi-day events and continuous UER events. Similarly, injury rates and diagnosis of MSKI during competition and training may also vary, as during competitions athletes typically push themselves to the limit. Several review articles of illness and injuries exist about ultramarathon running, however, they have not specifically reviewed MSKI in different types of UER events and analyzed MSKI in competition and training (Khodaee and Ansari, 2012;Lopes et al., 2012;Krabak et al., 2013Krabak et al., , 2014Knechtle and Nikolaidis, 2018a,b). Proper treatment of injuries and illnesses in UER is important for avoiding long-term issues (Krabak et al., 2014) and therefore it is important to examine and summarize MSKI within these broad categories of UER during competition and training.
The aims of this scoping review were therefore: (1) to examine the current evidence of MSKI, providing a synthesis of the most common MSKI by anatomical region and specific diagnosis; (2) categorize MSKI by type of UER activity (competition: timelimited; multi-stage; continuous UER events) and training); (3) describe knowledge gaps in the literature and provide advice on potential further research.

MATERIALS AND METHODS
This review is based on the recommendations for scoping reviews, with the purpose of identifying and mapping the available evidence and identifying knowledge gaps (Armstrong et al., 2011). As such we used a broad research question, for example: what are the musculoskeletal injuries in UER? What are the different anatomical distributions and incidence/prevalence of MSKI in UER competition and training? Our aim was to review the existing literature, summarize those findings, identify knowledge gaps, as done in previous scoping reviews (Armstrong et al., 2011;Granacher et al., 2016). The review considered scientific papers that investigated MSKI in UER. UER is defined as a broad category with different types of running activities, such as running events by distance in excess of 42.195 km (standard marathon distance), timed-events over 6 h durations, and multi-day or multi stage running events, on all surfaces (road, off-road, track) and terrains (Scheer et al., 2020a). All studies that examined MSKI in UER were included irrespective of participants age and/or sex, however, detailed information of MSKI according to sex or age was not available in the majority of studies, therefore a comprehensive breakdown of MSKI according to these parameters was not possible. However, those studies that did provide specific results on age and/or sex aspects were highlighted in the respective sections in the discussion (Micklesfield et al., 2007;Scheer et al., 2020d).
An electronic literature search was performed using different databases (PubMed, SPORTDiscus, Web of Science) from January 1st, 1984-September 30th, 2020. The following search terms were used: 'ultra endurance running' or 'ultra running' or 'ultramarathon' or 'trail running' or 'ultra trail running' and 'injury' or 'musculoskeletal injury' or 'muscle injury. ' We identified a total of 771 studies meeting our initial search criteria. Figure 1 gives an overview of article selection process in accordance with PRISMA (Moher et al., 2009). After removal of duplicates, the abstracts of the remaining 229 studies were reviewed. Only studies written in the English language were considered. Studies that did not examine MSKI in UER, did not provide any data on general or specific MSKI, provided data on mixed population (e.g., different running populations including UER and non-UER) were excluded. Similarly, studies that only examined muscle damage from biochemical markers or muscle cramps, as well as case reports were not included in this review. Studies on blisters, dermatological or other illnesses and injuries were excluded. A total of 35 full texts were assessed for eligibility and after review, a total of 13 studies met our inclusion criteria and were therefore included in the review. All abstracts and manuscript were reviewed by the two authors.
The definitions of MSKI varied across the different studies, with some providing no specific definitions (Scheer and Murray, 2011;Graham et al., 2012;McGowan and Hoffman, 2015;Dawadi et al., 2020), whereas other defined MSKI as a disability resulting in a medical encounter (Krabak et al., 2011;Vernillo et al., 2016), or affecting performance (Bishop and Fallon, 1999). All studies reporting MSKI during a race were either documented by the attending medical team (through self-referral/self-reporting system via medical encounters) or by a routine daily medical assessment questionnaire (Hutson, 1984;Fallon, 1996;Bishop and Fallon, 1999;Krabak et al., 2011;Scheer and Murray, 2011;Graham et al., 2012;McGowan and Hoffman, 2015;Vernillo et al., 2016;Dawadi et al., 2020). Studies examining MSKI in training studies defined injuries as either an athlete reporting the diagnosis based on a health care provider encounter or through athlete self-assessment (Micklesfield et al., 2007;Hoffman and Krishnan, 2014;Malliaropoulos et al., 2015;Scheer et al., 2020d).

RESULTS
The main findings of our review were: (i) MSKI in UER are common, mostly affecting the lower limbs and are of overuse in nature; (ii) MSKI differ between competition and training, with multistage events, predominantly affecting the lower leg, foot, and knee, while timed events mainly affect the ankle, Achilles tendon, and knee; (iii) Short continuous UER events off-road have the highest incidence of MSKI, mainly affecting the foot and ankle, while long continuous UER affect the knee and ankle; (iv) During training back, knee and bone stress injuries are common. Detailed description of MSKI incidence (rate of occurrences of new cases) and/or prevalence (number of MSKI at a particular time) are provided. The manuscript is organized accordingly describing the different pertinent research sections.
Thirteen studies examined MSKI in UER and are included in this review. Table 1 and Table 2 provide detailed information about the study, participants (age and sex), and MSKI. Nine studies (Table 1) provide information from UER races/competitions (total n = 723 participants), while four studies (Table 2) provide information from MSKI mostly during training of UER athletes (total n = 1606 participants). Detailed information of MSKI according to sex or age was not available in the majority of studies, therefore a comprehensive breakdown of MSKI according to sex or age was not possible. One study (Micklesfield et al., 2007) specifically examined bone stress injuries in female UER, and another MSKI in youth athletes (Scheer et al., 2020d) and for those studies results by sex and age were discussed in more detail in the appropriate sections. The vast majority of MSKI involve the lower limb (Fallon, 1996;Krabak et al., 2011), and are generally minor across all types of UER (Fallon, 1996;Bishop and Fallon, 1999;Krabak et al., 2014). MSKI are predominantly overuse in nature (e.g., tendinopathies), even during competitions, with incidences in the region of between 98-100% (Fallon, 1996;Bishop and Fallon, 1999), demonstrating the exceptional demand on the musculoskeletal system during prolonged running, in contrast to 'true' acute injuries (e.g., muscle strains) that may be expected during competition in other, more explosive sports (Huxley et al., 2014;Krabak et al., 2014;Scheer and Murray, 2015).

Ankle
The ankle is another frequently injured anatomical site and some investigations cite this as the most common site of injury in UER during competition, however, there was a wide range of incidences of between 16.8% (Krabak et al., 2011) to 36% (Bishop and Fallon, 1999). Tendinitis of the dorsiflexors of the foot was the most frequent diagnosis (29.6%) (Hutson, 1984) and called 'ultramarathon ankle, ' a relatively specific injury to UER (Hutson, 1984;Fallon, 1996;Bishop and Fallon, 1999;Scheer and Murray, 2011). Repetitive plantar and dorsiflexion as observed during prolonged running, may cause a peritendinitis/tenosynovitis of the tendons passing under or adjacent to the extensor retinaculum of the ankle (Hutson, 1984;Fallon, 1996). Other causative factors include excessive pressure on the dorsum of the ankle due to tight fitting shoes, over-pronation, running on hard surfaces, and overstriding (Hutson, 1984;Fallon, 1996). The incidence varied and was as low as 1.4% (Scheer and Murray, 2011) and reached 29.6% (Hutson, 1984). More specifically, depending which dorsiflexor of the foot was affected the incidence varied [e.g., extensor digitorum longus 7.8% (Fallon, 1996) to 14% (Bishop and Fallon, 1999); or extensor hallucis longus 3.1% (Fallon, 1996)].

Bone Stress Injuries of the Lower Limbs
Bone stress injuries can vary in severity, with early injuries demonstrating periosteal edema and/or bone marrow edema on radiological examination, with more severe injury showing a stress fractures with radiological evidence of a fracture line (Tenforde et al., 2016).
Stress fractures are usually fatigue fractures that develop through overuse on healthy bone (Harrast and Colonno, 2010;Pegrum et al., 2012;Krabak et al., 2019;Tenforde et al., 2019). None of the studies during competition described stress fractures, however, this may be difficult to diagnose clinically. Prevalence is high in training, ranging from 6.4% in youth UER (Scheer et al., 2020d) to 22% in adults (Malliaropoulos et al., 2015). Bone stress was particularly high among female athletes (21%) (Micklesfield et al., 2007), however, it is not clear from the study if these were early bone stress injuries or actual stress fractures. Bone stress injuries in female athletes were associated with increased energy expenditure, and associated with inadequate nutrition as seen in relative energy deficiency in sport (RED-S) (Micklesfield et al., 2007;Tiller et al., 2021). Prevalence of stress fractures in adult UER were observed in different anatomical regions, such as the foot (3.4%), tibia (1.9%), and femur/hip (0.5%) (Hoffman and Krishnan, 2014) and in youth athletes tibia (10.7%), and foot (3.6%) (Scheer et al., 2020d).

MSKI During Time-Limited UER on Track
Though research is limited, two studies compared MSKI during a 6 day time-limited UER events on a track (Hutson, 1984;Bishop and Fallon, 1999). One race was held on a tartan track with a change of running direction every 12 h (Hutson, 1984), and competitors averaged 936 km over the 6 day period. The main anatomical site of injury was the ankle (48%), followed by the knee (26%), involving the extensor muscle-tendon structure of the ankle (41%) and the knee (26%), tendonitis of foot dorsiflexors (30%) and Achilles tendonitis (19%). In comparison, the other time-limited UER event was held on a grass track, with the mean distance covered of 836 km (Bishop and Fallon, 1999) and the ankle was the anatomical site most frequently injured (36%), followed by the knee (19%). The extensor -muscletendon complex of the ankle (25%) and knee (22%) was less commonly affected, as well as tendonitis of the foot dorsiflexors (14%). The occurrence of Achilles tendonitis (19%) was similar (Bishop and Fallon, 1999).

MSKI During Multi-Stage, Multi-Day UER Events in Off-Road Terrain
Four studies examined MSKI during multi-day UER events on off-road terrain (Krabak et al., 2011;Scheer and Murray, 2011;Graham et al., 2012;Dawadi et al., 2020). They were all similar and comparable in length, and duration, of between 5 to 7 days, covering 219-240 km but differed in environmental conditions, with 3 of them in hot or desert environment (Krabak et al., 2011;Scheer and Murray, 2011;Graham et al., 2012) and one in cold environment, at altitude (Dawadi et al., 2020). Although two studies (Graham et al., 2012;Dawadi et al., 2020) did not provide specific diagnosis or incidences of MSKI, all injuries were minor and patterns observed were comparable to previous studies (Graham et al., 2012). The rate of MSKI were similar in three of the studies (17.0, 17.4, and 18.2%, respectively), varying between 0.7 injuries/runner and 1.8 injuries/runner (Krabak et al., 2011;Scheer and Murray, 2011;Dawadi et al., 2020). MSKI injury rates were reported in two studies but used different denominators, with a desert race reporting (minor MSKI 670.0 injuries/1000 runners; major MSKI 11.2 injuries/1000 h; overall 7.2 injuries/1000 h) (Krabak et al., 2011) and a race in the Himalaya (170 injuries/1000 runners or 1.2 cases per 1000 km) (Dawadi et al., 2020).Most MSKI were minor, occurred during the middle part of the race (around day 3 and 4) and affected the lower limbs, mainly lower leg, knee, ankle and foot (Krabak et al., 2011;Scheer and Murray, 2011). Two study showed a predominance of the lower leg/foot/ankle, whereas the other reported injuries mostly to the knee and ankle (Krabak et al., 2011;Scheer and Murray, 2011;Dawadi et al., 2020). The number of runners withdrawing from the race because of MSKI was also very similar (1.2% vs 1.4%) (Krabak et al., 2011;Scheer and Murray, 2011) with no withdrawals because of MSKI in the other two studies (Graham et al., 2012;Dawadi et al., 2020).

MSKI During Continuous UER Events
Three studies examined single, continuous UER events of different terrain and distance. While two races were held on offroad terrain, with distances of 65 km and 161 km (McGowan and Hoffman, 2015;Vernillo et al., 2016), the third was a road race over 10005 km (Fallon, 1996). The study examining the 161 km race was a retrospective analysis of medical encounters of four past edition of the same race, but did not provide specific anatomical distribution and diagnosis of MSKI, but 2.6% of all starters sought medical advice for MSKI, mostly for sprains, strains, tendinitis or muscular pain (McGowan and Hoffman, 2015). Injury rates for the 65 km UER event where high, with 614 injuries/1000 runners and 4285 injuries/1000 h (Vernillo et al., 2016). While MSKI were present in 32.8%, all were minor in nature, predominantly affecting the foot (plantar fasciitis), ankle and knee, with none of the runners having to withdrawal because of MSKI (Vernillo et al., 2016). Similarly, in the 10005 km road event, no runner had to withdrawal due to major MSKI, however, almost three quarters noticed a negative effect on performance (Fallon, 1996). Over 90% of MSKI affected the lower leg, with the main anatomical site the knee, ankle and foot (Fallon, 1996).

DISCUSSION
The aims of this scoping review were therefore: (1) to examine the current evidence of MSKI, providing a synthesis of the most common MSKI by anatomical region and specific diagnosis; (2) categorize MSKI by type of UER activity (competition: timelimited; multi-stage; continuous UER events and training); (3) describe knowledge gaps in the literature and provide advice on potential further research. The main findings of our review were that MSKI were mostly overuse injuries, predominantly affecting the lower limbs with different injury patterns and diagnosis between different types of UER activities.

Definition of MSKI
One of the challenges in comparing MSKI across the different studies was, that no uniform definition of MSKI was used. Some studies provided no specific definitions of MSKI (Scheer and Murray, 2011;Graham et al., 2012;McGowan and Hoffman, 2015;Dawadi et al., 2020), whilst others defined MSKI as a disability resulting in a medical encounter (Krabak et al., 2011;Vernillo et al., 2016), affecting performance (Bishop and Fallon, 1999), based on a diagnosis of a health care provider, or via self-assessment (Micklesfield et al., 2007;Hoffman and Krishnan, 2014;Malliaropoulos et al., 2015;Scheer et al., 2020d). Classifying and using a standard reporting systems of MSKI in UER is important, as lack of a standardized definition affects the rates of injuries and hinders comparison between studies (Kluitenberg et al., 2015;Yamato et al., 2015a,b). Further, most studies include small sample sizes, and therefore possibly influencing the rate of diagnosis, as with small changes in a particular diagnosis this can lead to large percentage differences. This may also be of particular interest in diagnoses that are made clinically during competitions, such as stress fractures or CECS. CECS is an overuse injury that presents with increased pressure within one of the compartments of the lower leg, that can lead to ischemia, decreased tissue perfusion and pain (Fraipont and Adamson, 2003;George and Hutchinson, 2012). The gold standard for diagnosis CECS is with compartmental pressure testing (Fraipont and Adamson, 2003;George and Hutchinson, 2012). This is not feasible during competition and diagnosis presented in the studies are made on clinical examination and suspicion. Therefore, some MSKI may be either underrepresented (e.g., stress fractures) or overrepresented (e.g., CECS) in small samples and not reflect the true incidence. Interestingly, none of the training studies reported on CECS, but a high number of stress fractures were observed, ranging from 6-22% (Micklesfield et al., 2007;Malliaropoulos et al., 2015;Scheer et al., 2020d).
Future studies therefore should consider examining MSKI on larger populations, either in larger races, pooling data from similar events or over several editions of the same event, to provide a better understanding of the incidence of MSKI. Similarly, it is important to examine different type of events as the limited research has shown, that MSKI are distributed differently depending on type of UER.

MSKI Comparing Different UER Events
During two 6 day time-limited UER events on the track, with an average distances of 836-936 km, the main anatomical site of injury was the ankle (36-48%) and the knee (19-26%), with tendonitis of foot dorsiflexors (25-41%) and Achilles tendonitis (19%) as the most frequent diagnosis (Hutson, 1984;Bishop and Fallon, 1999). Running on a loop-course of track may put additional stress on one particular anatomical side, however, in both studies injuries were evenly distributed between the left and right limb (Hutson, 1984;Bishop and Fallon, 1999), demonstrating that a changing of the running direction while running on a track, may help in preventing lower limb injuries (Gajda et al., 2020). Although, the lower limb was also commonly injured during multi-day UER events (ranging between 219 km-240 km) the distribution of MSKI differed [lower leg (35%), ankle (16.8%), knee (13.1%), and foot (12.6%)], with 0.2-1.8 injuries/runner and overall incidence of 7.2 injuries/1000 h or 1.2 injuries/1000 km (Krabak et al., 2011;Scheer and Murray, 2011;Graham et al., 2012;Dawadi et al., 2020). However, by comparison the overall distance covered in the same time period was very different (219-240 km vs. 836-936 km), that may be result in different injury patterns.
Three studies examined continuous UER events, ranging from 65 km to 10005 km (Fallon, 1996;McGowan and Hoffman, 2015;Vernillo et al., 2016). The shortest (65 km) race reported the highest number of MSKI (32%), with injury rates of 614 injuries/1000 runners and 4285 injuries/1000 h, with the main anatomical site, the foot (28.6%), ankle (28.6%) and knee (14.3%) (Vernillo et al., 2016). This represents the highest incidence of any UER event, possibly related to the off-road (trail) environment where the race was held, with significant elevation change and prolonged uphill and downhill running sections. Ankle and knee injuries were mostly diagnosed as sprains, possibly more related to acute injuries than true overuse injuries, although no further clinical assessment or diagnostic criteria are provided (Vernillo et al., 2016). But it is also possible that due to the short nature of the race, the running speed was comparatively faster compared to the other races, making injuries more likely. During a 1005 km road race, overuse MSKI were common with over 90% affecting the lower leg (31.3% knee, 28.1% ankle) (Fallon, 1996). The 161 km does not provide specific anatomical distribution and diagnosis of MSKI, but overall 2.6% of all starters sought medical advice for MSKI, mostly for sprains, strains, tendinitis or muscular pain (McGowan and Hoffman, 2015).

MSKI During Training
Although training studies also showed a predominance for lower limb MSKI, bone stress and stress fractures were commonly reported in contrast to data from competition, ranging from 6-21% (Micklesfield et al., 2007;Malliaropoulos et al., 2015;Scheer et al., 2020d), likely due to the longer observational periods and better diagnostic possibilities. Similarly, back injuries are rarely reported during competition but during training this varies between 12.4%-14%, although it may not always be directly related to running but to other activities of daily living (Hoffman and Krishnan, 2014;Malliaropoulos et al., 2015). Injury rates during training were between 1.9 and 3.4 injuries/athlete (Malliaropoulos et al., 2015;Scheer et al., 2020d), which is higher compared to injury rates during most competitions (0.7-2.1 injuries/runner) (Bishop and Fallon, 1999;Krabak et al., 2011;Scheer and Murray, 2011), possibly demonstrating the effects of continued large training loads and/or inadequate rest days. The highest injury rates were observed in a 65 km off-road UER event with 4.3 injuries/runner (Vernillo et al., 2016), suggesting that the demand of short and faster off-road events may have higher incidences of MSKI.

Practical Considerations
These findings may be of interest to a variety of practitioners. Firstly, medical practitioners and health care providers may be able to plan medical provisions when attending UER competitions. There is guidance on how to provide medical care at UER events , however, given the increased risk of MSKI during shorter, off-road UER events, these provisions may need to be adapted and/or increased. Similarly, medical practitioners may be able to treat training injuries more appropriately, especially considering the increased risk of bone stress injuries and back injuries during training. Secondly, coaches and athletes may benefit of the knowledge of the distribution of injuries and type of UER activity and plan their training program accordingly to try and avoid these overuse injuries.

Future Research Directions
Sports scientist and researchers may benefit from the synthesis of the available evidence and suggestions for future reference, helping them design further studies to reduce the knowledge gap. Examining different UER events, environments and surfaces may therefore also help to gain a better understanding of the underlying mechanisms of MSKI. Prior running experience and training history of the athlete as well as prior personal injury history may also be important and should be investigated. This may help to evaluate the impact of MSKI on race performance and withdrawal, as MSKI can lead to performance decrement (Fallon, 1996) and race withdrawal in 0.7%-4.8% of runners (Hutson, 1984;McGowan and Hoffman, 2015). Further, most studies include both sexes and sex difference have not been examined separately, however, it may be of interest as in non-UER females have more bone stress injuries while male runners more Achilles tendon injuries, although overall injury rates in non-UER athletes are similar (20.8 injuries/1000 females and 20.4 injuries/1000 males) (Hollander et al., 2021). Generally, there is less research in female UER, and it would be important to examine sex differences, as key aspects of female athlete physiology warrant careful consideration, e.g., RED-S that may lead to physiological impairments resulting in an increased risk of bone stress injuries (Tiller et al., 2021). Additionally, age differences in MSKI have not been examined, which is another important aspect, especially if UER could lead to negative longterm health effects on the musculoskeletal system.
Examination of risk factors leading to MSKI in UER is another important aspect as there seems to be a U-shaped pattern between the running distance and the time-loss injury (Kluitenberg et al., 2015). Especially in UER, that requires large training volumes this will be an important aspect, as well as strategies to reduce MSKI. MSKI may be reduced through online tailored advice and this has been observed in trail runners participating in distances of between 15-62 km (Hespanhol et al., 2018), however, if this is particularly applicable to UER is not known but an interesting aspect to investigate further. It may also be interesting to explore how long athletes have to refrain from UER after a MSKI or if they part take in other sports (e.g., cycling) either during rehab or stop UER altogether.

CONCLUSION
Musculoskeletal injuries in UER are common, mostly affecting the lower limb and are of overuse in nature. MSKI differ between competition and training, with multistage events, predominantly affecting the lower leg (medial tibial stress syndrome), foot, knee (patella femoral pain syndrome (PFPS), while timed events mainly affect the ankle (tendinitis of the foot dorsiflexors, Achilles tendinopathy), and knee (patellar tendinopathy). Short continuous UER events off-road have the highest incidence of MSKI, mainly affecting the foot (plantar fasciitis), ankle (ankle sprain), whereas in long continuous UER the main anatomical site of injury is the knee (PFPS), and ankle. During training the back, knee and bone stress injuries are common. Future considerations include examining MSKI in different UER events, environments and surfaces, and on larger study populations. Establishing risk factors, examining sex differences and using a standard reporting system of MSKI in UER are also important.

AUTHOR CONTRIBUTIONS
VS performed conception and design of the study, literature search and analysis, and manuscript writing and editing. BK performed literature search and analysis and manuscript writing and editing. Both authors contributed to the article and approved the submitted version.