Biomedical Risk Factors of Achilles Tendinopathy in Physically Active People: a Systematic Review

Sports Medicine - Open, May 2017

Background Achilles tendinopathy is the most prevalent tendon disorder in people engaged in running and jumping sports. Aetiology of Achilles tendinopathy is complex and requires comprehensive research of contributing risk factors. There is relatively little research focussing on potential biomedical risk factors for Achilles tendinopathy. The purpose of this systematic review is to identify studies and summarise current knowledge of biomedical risk factors of Achilles tendinopathy in physically active people. Methods Research databases were searched for relevant articles followed by assessment in accordance with PRISMA statement and standards of Cochrane collaboration. Levels of evidence and quality assessment designation were implemented in accordance with OCEBM levels of evidence and Newcastle-Ottawa Quality Assessment Scale, respectively. Results A systematic review of the literature identified 22 suitable articles. All included studies had moderate level of evidence (2b) with the Newcastle-Ottawa score varying between 6 and 9. The majority (17) investigated genetic polymorphisms involved in tendon structure and homeostasis and apoptosis and inflammation pathways. Overweight as a risk factor of Achilles tendinopathy was described in five included studies that investigated non-genetic factors. COL5A1 genetic variants were the most extensively studied, particularly in association with genetic variants in the genes involved in regulation of cell-matrix interaction in tendon and matrix homeostasis. It is important to investigate connections and pathways whose interactions might be disrupted and therefore alter collagen structure and lead to the development of pathology. Polymorphisms in genes involved in apoptosis and inflammation, and Achilles tendinopathy did not show strong association and, however, should be considered for further investigation. Conclusions This systematic review suggests that biomedical risk factors are an important consideration in the future study of propensity to the development of Achilles tendinopathy. The presence of certain medical comorbidities and genetic markers should be considered when contemplating the aetiology of Achilles tendinopathy. Further elucidation of biomedical risk factors will aid in the understanding of tendon pathology and patient risk, thereby informing prevention and management strategies for Achilles tendinopathy. Trial Registration PROSPERO CRD42016036558

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Biomedical Risk Factors of Achilles Tendinopathy in Physically Active People: a Systematic Review

Kozlovskaia et al. Sports Medicine - Open Biomedical Risk Factors of Achilles Tendinopathy in Physically Active People: a Systematic Review Maria Kozlovskaia 0 1 Nicole Vlahovich 0 Kevin J. Ashton 1 David C. Hughes 0 0 Department of Sports Medicine, Australian Institute of Sport , 1 Leverrier Street, Bruce, ACT 2617 , Australia 1 Faculty of Health Sciences and Medicine, Bond University , 14 University Drive, Robina, QLD 4226 , Australia Background: Achilles tendinopathy is the most prevalent tendon disorder in people engaged in running and jumping sports. Aetiology of Achilles tendinopathy is complex and requires comprehensive research of contributing risk factors. There is relatively little research focussing on potential biomedical risk factors for Achilles tendinopathy. The purpose of this systematic review is to identify studies and summarise current knowledge of biomedical risk factors of Achilles tendinopathy in physically active people. Methods: Research databases were searched for relevant articles followed by assessment in accordance with PRISMA statement and standards of Cochrane collaboration. Levels of evidence and quality assessment designation were implemented in accordance with OCEBM levels of evidence and Newcastle-Ottawa Quality Assessment Scale, respectively. Results: A systematic review of the literature identified 22 suitable articles. All included studies had moderate level of evidence (2b) with the Newcastle-Ottawa score varying between 6 and 9. The majority (17) investigated genetic polymorphisms involved in tendon structure and homeostasis and apoptosis and inflammation pathways. Overweight as a risk factor of Achilles tendinopathy was described in five included studies that investigated non-genetic factors. COL5A1 genetic variants were the most extensively studied, particularly in association with genetic variants in the genes involved in regulation of cell-matrix interaction in tendon and matrix homeostasis. It is important to investigate connections and pathways whose interactions might be disrupted and therefore alter collagen structure and lead to the development of pathology. Polymorphisms in genes involved in apoptosis and inflammation, and Achilles tendinopathy did not show strong association and, however, should be considered for further investigation. Conclusions: This systematic review suggests that biomedical risk factors are an important consideration in the future study of propensity to the development of Achilles tendinopathy. The presence of certain medical comorbidities and genetic markers should be considered when contemplating the aetiology of Achilles tendinopathy. Further elucidation of biomedical risk factors will aid in the understanding of tendon pathology and patient risk, thereby informing prevention and management strategies for Achilles tendinopathy. Trial Registration: PROSPERO CRD42016036558 Achilles tendinopathy; Risk factors; Biomedical risk factors; Genetics - Key Points Increased BMI and adverse lipid profile may be important biomarkers of Achilles tendinopathy. Further research is required to confirm an association between genetic variation, of genes encoding collagen proteins and proteins involved in pathways of tendon homeostasis and Achilles tendinopathy. Genetic risk factors of Achilles tendinopathy may be modified by geographic factors. Methods Literature Search Strategy This systematic review was registered in the international prospective register of systematic reviews Quality Assessment The quality of the included studies was evaluated applying the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control and cohort studies [20]. This assessment checklist is recommended by the Cochrane Handbook for Systematic Reviews of Interventions [18, 21]. The NOS checklist assesses quality of the articles in three domains: selection of the studied groups; comparability of the groups and control for confounding factors; and exposure for case-control studies or outcome for cohort studies. Total maximum score is nine for both types of studies. Results of the studies were critically analysed and presented in the narrative form reporting odds ratios (OR) and confidence intervals. selected articles. Levels of evidence could be identified according to the type of clinical question [22]. Results Presentation Results of the studies are described in narrative form, and odds ratios and confidence intervals or relative risks of developing Achilles tendinopathy are reported in Table 2 where possible. Levels of Evidence Oxford Centre for Evidence-based Medicine (OCEBM) levels of evidence was used as a guidance to evaluate Discussion The selected studies focused on a diverse range of biomedical risk factors for Achilles tendinopathy such as Fig. 1 PRISMA flowchart of the study selection process Abate et al. (2015) [41] Abrahams et al. (2013) [23] Brown et al. (2016) [36] El Khoury et al. (2016) [38] El Khoury et al. (2015) [35] El Khoury et al. (2013) [24] Gaida et al. (2009) [43] Gaida et al. (2010) [44] Gibbon et al. (2016) [37] Hay et al. (2013) [25] Longo et al. (2009) [42] Mokone et al. (2005) [26] Mokone et al. (2006) [27] Nell et al. (2012) [28] Owens et al. (2013) [40] Posthumus et al. (2010) [29] Raleigh (2009) [31] Rickaby et al. (2015) [39] Saunders et al. (2013) [30] September et al. (2008) [34] September et al. (2009) [33] September et al. (2011) [32] Total score 6 S ;) 8 om .l ro (2 .3 A A 4% r a f . 0 S M 17 S . frt te SU lta ,4N ;F .8% ,TA ;F ,23 6 S .2% M co ko 05 ieg S 5 N AU 82 .6% A o 0 l U , O ; , 7 S M (2 aR A M C F M 6 ± rt e AU te , .3 .8 S .5 .8 .4 .8 ho en ,) h ) NO 12 ,N 10 AU 14 , 14 25 11 o o 5 ig 9 C ± O ± ;) ± T ± , ± c k S .4 C .4 A .9 N .9 SA oM (200 laeR (200 U 9 A 6 154 .047 SA 40 O 4 A 3 S 3 ( C 5 exacerbated by physical load. Further elucidation of biomedical risk factors will aid in the understanding of tendon pathology and patient risk, thereby informing prevention and management strategies for Achilles tendinopathy. Funding Funding is provided by the Collaborative Research Network for Advancing Exercise & Sports Science (CRN-AESS). Authors’ Contributions MK contributed to the conception and design of the review and analysis and interpretation of the results and drafted the manuscript. 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Maria Kozlovskaia, Nicole Vlahovich, Kevin J. Ashton, David C. Hughes. Biomedical Risk Factors of Achilles Tendinopathy in Physically Active People: a Systematic Review, Sports Medicine - Open, 2017, 20, DOI: 10.1186/s40798-017-0087-y