Towards a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function', i.e. to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during 'normal' ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. The CIMA Toolkit Working Group assessed candidate biomarkers of musculoskeletal ageing under these four headings, detailed their biological bases, strengths and limitations, and made practical recommendations for their use. In addition, the CIMA Toolkit Working Group identified gaps in the evidence base and suggested priorities for further research on biomarkers of musculoskeletal ageing.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during 'normal' ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.

External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals.

BACKGROUND AND AIMS: Simple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy (1H-MRS). METHODS: Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment. Values of FLI and LAP were determined and assessed both as predictors of the presence of hepatic steatosis (liver fat>5.5%) and of actual liver fat content, as measured by 1H-MRS. The discriminative ability of FLI and LAP was estimated using the area under the receiver operator characteristic curve (AUROC). As FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Further validation was provided in 54 patients with type 2 diabetes mellitus. RESULTS: FLI, LAP and alanine transferase discriminated between patients with and without steatosis with an AUROC of 0.79 (IQR=0.74, 0.84), 0.78 (IQR=0.72, 0.83) and 0.83 (IQR=0.79, 0.88) respectively although could not quantitatively predict liver fat. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort. CONCLUSIONS: FLI and LAP may be used to identify patients with hepatic steatosis clinically or for research purposes but could not predict liver fat content.

Responsiveness of the Liverpool Elbow Score in elbow arthroplasty.

BACKGROUND: Responsiveness and floor and ceiling effect are important parameters for evaluating the sensitivity of an outcome instrument in detecting the changes in the clinical condition of patients after an intervention as well as evaluating the content validity of the instrument. The aim of this prospective observational study was to assess these parameters for the Liverpool Elbow Score (LES) in total elbow replacement (TER). METHODS: The study included 121 cemented TER cases with linked elbow prosthesis (Discovery Elbow, Biomet Orthopaedics, Swindon, UK) for various conditions, including inflammatory arthritis, noninflammatory arthritis, trauma, and loosening. The proportion of patients with the lowest score (0 points; floor effect) and maximum score (10 points; ceiling effect) was checked preoperatively and 1 year postoperatively. Distribution-based methods (effect size [ES], standardized response mean [SRM], Guyatt responsiveness ratio [GRR]) and anchor-based methods (receiver operating characteristic [ROC] curve and Spearman correlation coefficient) were used to assess responsiveness. Patient satisfaction after TER was used as an external anchor. RESULTS: Patients were a mean age of 63 years (range, 20-86 years). Large ES (1.64), SRM (1.25), and GRR (1.69) were found during the follow-up period. Area under the ROC curve was 0.71 (95% confidence interval, 0.56-0.87; P = .03). There was significant positive correlation (Spearman correlation coefficient, 0.35; P = .004) between changes in LES and satisfaction level. LES showed no floor and ceiling effect preoperatively and at 1 year postoperatively. CONCLUSION: LES is a responsive measure and has no floor and ceiling effect. LEVEL OF EVIDENCE: This encourages its use as an outcome instrument for TER. Basic Science Study, Development or Validation of Outcome Instruments.

Assessment of functional recovery in tennis elbow.

OBJECTIVES: (a) To investigate changes in muscular strength, fatigue and activity in recovered tennis elbow (RTE); (b) to assess the appropriateness of EMG and strength measurements in monitoring functional recovery in tennis elbow (TE). METHODS: Study included three age-matched female groups of Control (C) (n=8, no history of musculoskeletal problems), TE (n=7, local tenderness at the lateral epicondyle and pain with resisted wrist and middle finger extension) and RTE (n=6, asymptomatic for at least 6 months, no lateral epicondyle tenderness). Measurements included metacarpophalangeal (MCP), wrist, shoulder and grip isometric strength and EMG measures of muscle fatigue and activity for five forearm muscles (wrist extensors and flexors). RESULTS: Strength was greater (p<0.05) for all measurements in C compared to RTE and TE except for MCP extension. Only MCP extension was stronger in RTE than TE. EMG revealed increased activity of extensor carpi radialis (ECR) in RTE, decreased in TE. CONCLUSIONS: Despite attenuation of pain, global upper limb weakness in RTE indicated incomplete functional recovery. Increased strength of MCP extension may protect weakened wrist extensors from further injury. Monitoring the ECR activity as well as strength measurements may provide a useful assessment of functional recovery in TE.

Upper limb muscle imbalance in tennis elbow: a functional and electromyographic assessment.

The purpose of this study was to investigate strength, fatigability, and activity of upper limb musculature to elucidate the role of muscular imbalance in the pathophysiology of tennis elbow. Sixteen patients clinically diagnosed with tennis elbow, recruited from a university hospital upper limb orthopedic clinic, were compared with 16 control subjects with no history of upper limb musculoskeletal problem, recruited from university students and staff. Muscle strength was measured for grip, metacarpophalangeal, wrist, and shoulder on both sides. Electromyographic activity (RMS amplitude) and fatigue characteristics (median frequency slope) of five forearm and two shoulder muscles were measured during isometric contraction at 50% maximum voluntary contraction. All strength measurements showed dominance difference in C, but none in TE. In tennis elbow compared to controls, hand/wrist and shoulder strength and extensor carpi radialis (ECR) activity were reduced (p < 0.05), while fatigue was normal. A global upper limb weakness exists in tennis elbow. This may be due to disuse and deconditioning syndrome caused by fear avoidance, and needs to be addressed in prevention and treatment. Activation imbalance among forearm muscles (reduced extensor carpi radialis activity) in tennis elbow, probably due to protective pain-related inhibition, could lead to a widespread upper limb muscle imbalance.