Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

Multiple phenotypes characterized by different disease mechanisms have been hypothesized to explain the large variability in the knee osteoarthritis (KOA) population. The purpose of this study was: to estimate and compare the medial and lateral knee compression forces (CF) during gait of three subgroups of KOA subjects characterized by different alignment and cartilage disruption patterns. A secondary data analysis was conducted on a sample of 39 KOA subjects and 18 controls (C). The patients were classified in the different groups according to the following criteria: Varus medial disease (VMD) (12): varus alignment and predominant medial cartilage degeneration Varus generalized disease (VGD) (17): varus alignment and cartilage degeneration that extends to the lateral compartment. Neutral alignment (NA) (10): neutral alignment. The total, medial and lateral CF corrected for body weight were estimated using an inverse dynamics model (AnyBody Modeling System, AnyBody Technology) during stance. The impulse of the medial compressive force (MCF) (overall effect of the CF over the stance) was significantly higher (P < 0.01) in the VMD compared to all the other groups. Peak MCF was higher in the VMD compared to all the other groups, but the difference reached significance only when compared to the VGD group (P < 0.05). The results of the regression analysis showed a significant relationship in the VMD group between alignment and impulse of the MCF (R² = 0.62; P < 0.01). This relationship disappears in the other groups. These findings suggest the existence of a phenotype characterized by increased MCF.

Explosive neuromuscular performance refers to the ability to rapidly increase force in response to neuromuscular activation. The lower explosive force production of the hamstrings relative to the quadriceps could compromise knee joint stability and increase the risk of anterior cruciate ligament injury. However, the time course of the rise in explosive force of the hamstrings and quadriceps from their initial activation, and thus the explosive hamstrings-to-quadriceps (H/Q) force ratio, has not been documented. The neuromuscular performance of 20 untrained males was assessed during a series of isometric knee flexion and extension contractions, with force and surface EMG of the hamstrings and quadriceps recorded during explosive and maximum voluntary contractions. Hamstrings force was expressed relative to quadriceps force to produce hamstring-to-quadriceps ratios of explosive H/Q force and H/Q maximum voluntary force. For the explosive contractions, agonist electromechanical delay (EMD), agonist and antagonist neural activation were assessed. The quadriceps was 79% stronger than the hamstrings, but quadriceps explosive force was up to 480% greater than the hamstrings from 25 to 50 ms after first activation. Consequently, the explosive H/Q force ratio was very low at 25 and 50 ms (0%-17%) and significantly different from H/Q maximum voluntary force ratio (56%). Hamstrings EMD was 95% greater than quadriceps EMD (44.0 vs 22.6 ms), resulting in a 21-ms later onset of force in the hamstrings that appeared to explain the low explosive H/Q force ratio in the early phase of activation. Prolonged hamstrings EMD appears to impair early phase (0-50 ms) explosive force production relative to the quadriceps and may render the knee unstable and prone to anterior cruciate ligament injury during this period.

Lower limb muscle dysfunction is a key driver for impaired physical capacity and frailty status, both characteristics of sarcopenia. Sarcopenia is the key pathway between frailty and disability. Identifying biological markers for early diagnosis, treatment, and prevention may be key to early intervention and prevention of disability particularly mobility issues. To identify biological markers associated with lower limb muscle (dys)function in adults with sarcopenia, a systematic literature search was conducted in AMED, CINAHL, Cochrane Library, EMBASE, Medline, PubMed, Scopus, SPORTDiscus, and Web of Science databases from inception to 17 November 2021. Title, abstract, and full‐text screening, data extraction, and methodological quality assessment were performed by two reviewers independently and verified by a third reviewer. Depending on available data, associations are reported as either Pearson's correlations, regression R² or partial R², P value, and sample size (n). Twenty eligible studies including 3306 participants were included (females: 79%, males: 15%, unreported: 6%; mean age ranged from 53 to 92 years) with 36% in a distinct sarcopenic subgroup (females: 73%, males: 19%, unreported: 8%; mean age range 55–92 years). A total of 119 biomarkers were reported, categorized into: genetic and microRNAs (n = 64), oxidative stress (n = 10), energy metabolism (n = 18), inflammation (n = 7), enzyme (n = 4), hormone (n = 7), bone (n = 3), vitamin (n = 2), and cytokine (n = 4) markers) and seven lower limb muscle measures predominately focused on strength. Seven studies reported associations between lower limb muscle measures including (e.g. power, force, and torque) and biomarkers. In individuals with sarcopenia, muscle strength was positively associated with free testosterone (r = 0.40, P = 0.01; n = 46). In analysis with combined sarcopenic and non‐sarcopenic individuals, muscle strength was positively associated with combined genetic and methylation score (partial R² = 0.122, P = 0.03; n = 48) and negatively associated with sarcopenia‐driven methylation score (partial R² = 0.401, P < 0.01; n = 48). Biomarkers related to genetics (R² = 0.001–0.014, partial R² = 0.013–0.122, P > 0.05; n = 48), oxidative stress (r = 0.061, P > 0.05; n ≥ 77), hormone (r = 0.01, ρ = 0.052 p > 0.05, n ≥ 46) and combined protein, oxidative stress, muscle performance, and hormones (R² = 22.0, P > 0.05; n ≥ 82) did not report significant associations with lower limb muscle strength. Several biomarkers demonstrated associations with lower limb muscle dysfunction. The current literature remains difficult to draw clear conclusions on the relationship between biomarkers and lower limb muscle dysfunction in adults with sarcopenia. Heterogeneity of biomarkers and lower limb muscle function precluded direct comparison. Use of international classification of sarcopenia and a set of core standardized outcome measures should be adopted to aid future investigation and recommendations to be made.