Aims. Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters. Methods. We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis. Results. The studies assessed different hip conditions like labrum status, the biomechanical effect of the cam, femoral version, acetabular coverage, and the effect of rim trimming. The testing and loading conditions were also quite diverse, and this disparity limits direct comparisons between the different researches. With normal anatomy the mean contact pressures ranged from 1.54 to 4.4 MPa, and the average peak contact pressures ranged from 2 to 9.3 MPa. Labral tear or resection showed an increase in contact pressures that diminished after repair or reconstruction of the labrum. Complete cam resection also decreased the contact pressure, and acetabular rim resection of 6 mm increased the contact pressure at the acetabular base. Conclusion. To date there is no standardized methodology to access hip contact biomechanics in hip arthroscopy, or with the preservation of the periarticular soft-tissues. A tendency towards improved biomechanics (lower contact pressures) was seen with labral repair and reconstruction techniques as well as with cam correction. Cite this article: Bone Joint Res 2023;12(12):712–721

Aims. Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years. Methods. Systematic literature searches identified all clinical studies reporting outcomes for adults following open lower limb fracture between January 2009 and July 2019. All outcomes and outcome measurement instruments were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using an outcome taxonomy. Results. A total of 532 eligible studies were identified, reporting 1,803 outcomes with 786 unique outcome terms, which collapsed to 82 standardized outcome headings. Overall 479 individual outcome measurement instruments were identified, including 298 outcome definitions, 27 patient- and 18 clinician-reported outcome measures, and six physical performance measures. The most-reported outcome was ‘bone union/healing’ reported in over 50% of included studies, while health-related quality of life was only measured in 6% of included studies. Conclusion. Outcomes reported for people recovering from open lower limb fracture are heterogeneous, liable to outcome reporting bias, and vary widely in the definitions and the measurement tools used to collect them. Outcomes likely to be important to patients, such as quality of life and measures of physical functioning, have been neglected. This systematic review identifies the need to unify outcome measures reported on patients recovering from open lower limb fracture; this may be addressed by creating a core outcome set. Cite this article: Bone Joint Res 2023;12(2):138–146

Aims. The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA). Methods. Electronic literature searches were conducted using MEDLINE, Embase, PubMed, and Cochrane. All studies reporting prognostic estimates for factors associated with the revision of a primary TEA were included. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and the quality of evidence was assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Due to low quality of the evidence and the heterogeneous nature of the studies, a narrative synthesis was used. Results. A total of 19 studies met the inclusion criteria, investigating 28 possible prognostic factors. Most QUIPS domains (84%) were rated as moderate to high risk of bias. The quality of the evidence was low or very low for all prognostic factors. In low-quality evidence, prognostic factors with consistent associations with failure of TEA in more than one study were: the sequelae of trauma leading to TEA, either independently or combined with acute trauma, and male sex. Several other studies investigating sex reported no association. The evidence for other factors was of very low quality and mostly involved exploratory studies. Conclusion. The current evidence investigating the prognostic factors associated with failure of TEA is of low or very low quality, and studies generally have a moderate to high risk of bias. Prognostic factors are subject to uncertainty, should be interpreted with caution, and are of little clinical value. Higher-quality evidence is required to determine robust prognostic factors for failure of TEA. Cite this article: Bone Joint Res 2024;13(5):201–213

Aims. Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. Methods. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction. Results. When all ethnicities were combined the mean values for LL, SS, PT, and PI were: 47.4° (SD 11.0°), 35.8° (SD 7.8°), 14.0° (SD 7.2°), and 48.8° (SD 10°), respectively. LL, SS, and PT had statistically significant (p < 0.001) changes per decade at: −1.5° (SD 0.3°), −1.3° (SD 0.3°), and 1.4° (SD 0.1°). Asian populations had the largest age-dependent change in LL, SS, and PT compared to any other ethnicity per decade at: −1.3° (SD 0.3°) to −0.5° (SD 1.3°), –1.2° (SD 0.2°) to −0.3° (SD 0.3°), and 1.7° (SD 0.2°) versus 1.1° (SD 0.1°), respectively. Conclusion. Ageing alters the orientation between the spine and pelvis, causing LL, SS, and PT to modify their orientations in a compensatory mechanism to maintain sagittal alignment for balance when standing. Asian populations have the largest degree of age-dependent change to their spinopelvic parameters compared to any other ethnicity, likely due to their lower PI. Cite this article: Bone Joint Res 2023;12(4):231–244

Aims. The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates. Methods. PubMed (National Library of Medicine) and Scopus (Elsevier) databases were searched. Articles were eligible for inclusion if they reported incidence rate (or count with population at risk), contained data on adult population, and were written in English language. The number of cases and population at risk were collected, and the pooled incidence rates (per 100,000 person-years) with 95% confidence intervals (CIs) were calculated by using either a fixed or random effects model. Results. The screening of titles yielded 206 articles eligible for inclusion in the study. Of these, 173 (84%) articles provided sufficient information to be included in the pooled incidence rates. Incidences of fractures were investigated in 154 studies, and the most common fractures in the whole adult population based on the pooled incidence rates were distal radius fractures (212.0, 95% CI 178.1 to 252.4 per 100,000 person-years), finger fractures (117.1, 95% CI 105.3 to 130.2 per 100,000 person-years), and hip fractures (112.9, 95% CI 82.2 to 154.9 per 100,000 person-years). The most common sprains and dislocations were ankle sprains (429.4, 95% CI 243.0 to 759.0 per 100,000 person-years) and first-time patellar dislocations (32.8, 95% CI 21.6 to 49.7 per 100,000 person-years). The most common injuries were anterior cruciate ligament (17.5, 95% CI 6.0 to 50.2 per 100,000 person-years) and Achilles (13.7, 95% CI 9.6 to 19.5 per 100,000 person-years) ruptures. Conclusion. The presented pooled incidence estimates serve as important references in assessing the global economic and social burden of musculoskeletal injuries. Cite this article: Bone Joint Res 2022;11(11):814–825

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Aims. The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone. Methods. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software. Results. A total of 20 studies with 2,123 hips were included (CD alone = 768, CD combined with other treatments = 1,355). The combination of CD with other therapeutic interventions resulted in a higher HHS (mean difference (MD) = 6.46, 95% confidence interval (CI) = 2.10 to 10.83, p = 0.004) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = −10.92, 95% CI = -21.41 to -4.03, p = 0.040) and a lower visual analogue scale (VAS) score (MD = −0.99, 95% CI = -1.56 to -0.42, p < 0.001) than CD alone. For the rates of disease stage progression, 91 (20%) progressed in the intervention group compared to 146 (36%) in the control group (odds ratio (OR) = 0.32, 95% CI = 0.16 to 0.64, p = 0.001). In addition, the intervention group had a more significant advantage in delaying femoral head progression to the collapsed stage (OR = 0.32, 95% CI = 0.17 to 0.61, p < 0.001) and reducing the odds of conversion to THA (OR = 0.35, 95% CI = 0.23 to 0.55, p < 0.001) compared to the control group. There were no serious adverse events in either group. Subgroup analysis showed that the addition of cell therapy significantly improved clinical and radiological outcomes compared to CD alone, and this approach appeared to be more effective than other therapies, particularly in precollapse (stage I to II) ONFH patients. Conclusion. There was marked heterogeneity in the studies. There is a trend towards improved clinical outcomes with the addition of stem cell therapy to CD. Cite this article: Bone Joint Res 2021;10(7):445–458

Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results. A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion. Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51–59

Aims. A systematic literature review focusing on how long before surgery concurrent viral or bacterial infections (respiratory and urinary infections) should be treated in hip fracture patients, and if there is evidence for delaying this surgery. Methods. A total of 11 databases were examined using the COre, Standard, Ideal (COSI) protocol. Bibliographic searches (no chronological or linguistic restriction) were conducted using, among other methods, the Patient, Intervention, Comparison, Outcome (PICO) template. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for flow diagram and checklist. Final reading of the complete texts was conducted in English, French, and Spanish. Classification of papers was completed within five levels of evidence (LE). Results. There were a total of 621 hits (526 COre; 95 Standard, Ideal) for screening identification, and 107 records were screened. Overall 67 full-text articles were assessed for eligibility, and 21 articles were included for the study question. A total of 46 full-text articles were excluded with reasons. No studies could be included in quantitative synthesis (meta-analyses), and there were many confounding variables including surgeons’ experience, prosthesis models used, and surgical technique. Conclusion. Patients with hip fracture and with a viral infection in the upper respiratory tract or without major clinical symptoms should be operated on as soon as possible (LE: I-III). There is no evidence that patients with coronavirus disease 2019 (COVID-19) should be treated differently. In relation to pneumonia, its prevention is a major issue. Antibiotics should be administered if surgery is delayed by > 72 hours or if bacterial infection is present in the lower respiratory tract (LE: III-V). In patients with hip fracture and urinary tract infection (UTI), delaying surgery may provoke further complications (LE: I). However, diabetic or immunocompromised patients may benefit from immediate antibiotic treatment. Cite this article: Bone Joint Res 2020;9(12):884–893

Aims. The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP. Methods. PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR. Results. Six studies with 1,255 cases were included (374 PJI cases and 881 non-PJI cases). Overall D-dimer showed sensitivity of 0.80 (95% confidence interval (CI) 0.69 to 0.87) and specificity of 0.76 (95% CI 0.63 to 0.86). Sub-group analysis by excluding patients with thrombosis and hyper-coagulation disorders showed sensitivity of 0.82 (95% CI 0.70 to 0.90) and specificity of 0.80 (95% CI 0.70 to 0.88). Serum D-dimer showed sensitivity of 0.85 (95% CI 0.76 to 0.92), specificity of 0.83 (95% CI 0.74 to 0.90). Plasma D-dimer showed sensitivity of 0.67 (95% CI 0.60 to 0.73), specificity of 0.58 (95% CI 0.45 to 0.72). CRP showed sensitivity of 0.78 (95% CI 0.72 to 0.83), specificity of 0.81 (95% CI 0.72 to 0.87). ESR showed sensitivity of 0.68 (95% CI 0.63 to 0.73), specificity of 0.83 (95% CI 0.78 to 0.87). Conclusion. In patients without thrombosis or a hyper-coagulation disorder, D-dimer has a higher diagnostic value compared to CRP and ESR. In patients with the aforementioned conditions, D-dimer has higher sensitivity but lower specificity compared to ESR and CRP. We do not recommend the use of serum D-dimer in patients with thrombosis and hyper-coagulation disorders for diagnosing PJI. Serum D-dimer may perform better than plasma D-dimer. Further studies are needed to compare serum D-dimer and plasma D-dimer in arthroplasty patients. Cite this article: Bone Joint Res 2020;9(10):701–708

Aims. To systematically review the outcomes and complications of cosmetic stature lengthening. Methods. PubMed and Embase were searched on 10 November 2019 by three reviewers independently, and all relevant studies in English published up to that date were considered based on predetermined inclusion/exclusion criteria. The search was done using “cosmetic lengthening” and “stature lengthening” as key terms. The Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement was used to screen the articles. Results. A total of 11 studies including 795 patients were included. The techniques used in the majority of the patients were classic 3- or 4-ring Ilizarov fixator (267 patients; 33.6%) and lengthening over nail (LON) (253 patients; 31.8%), while implantable lengthening nail (ILN) was used in the smallest number of patients (63 patients; 7.9%). Mean end lengthening achieved was 6.7 cm (SD 0.6; 1.5 to 13.0), and the mean follow-up duration was 4.9 years (SD 2.1; 41 days to 7 years). Overall, the mean number of problems, obstacles, and complications per patient was 0.78 (SD 0.5), 0.94 (SD 1.0), and 0.15 (SD 0.2), respectively. The most common problem and obstacle was ankle equinus deformity, while the most common complications were deformation of the regenerate after end of treatment and subtalar joint stiffness/deformity. Conclusion. Cosmetic stature lengthening provides favourable height gain, patient satisfaction, and functional outcomes, with low rate of major complications. Clear indications, contraindications, and guidelines for cosmetic stature lengthening are needed. Cite this article: Bone Joint Res 2020;9(7):341–350

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties.

Cite this article: Bone Joint Res 2021;10(3):203–217.

Aims. Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods. The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results. Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion. Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article:Bone Joint Res. 2020;9(3):120–129

Aims. Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results. The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion. The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article:Bone Joint Res. 2020;9(3):108–119

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

Objectives. Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified. Methods. We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included. Results. IL-1β, IL-6, IL-10, and TNF-α are the cytokines that have been most frequently investigated. In clinical samples of tendinopathy and tendon tears, the expression of TNF-α tended not to change but IL-6 increased in tears. Healthy human tendons showed increased IL-6 expression after exercise; however, IL-10 remained unchanged. Animal tendon injury models showed that IL-1β, IL-6, and TNF-α tend to increase from the early phase of tendon healing. In animal exercise studies, IL-1β expression showed a tendency to increase at the early stage after exercise, but IL-10 expression remained unchanged with exercise. Conclusions. This review highlights the roles of IL-1β, IL-6, IL-10, and TNF-α in the development of tendon disease, during tendon healing, and in response to exercise. However, there is evidence accumulating that suggests that other cytokines are also contributing to tendon inflammatory processes. Further work with hypothesis-free methods is warranted in order to identify the key cytokines, with subsequent mechanistic and interaction studies to elucidate their roles in tendon disease development. Cite this article: W. Morita, S. G. Dakin, S. J. B. Snelling, A. J. Carr. Cytokines in tendon disease: A Systematic Review. Bone Joint Res 2017;6:656–664. DOI: 10.1302/2046-3758.612.BJR-2017-0112.R1