This study was conducted in compliance with the Declaration of Helsinki and was approved by The Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee (Ethics approval number: 2015.539). Study registration was made with the US ClinicalTrials.gov (NCT03579329).
This prospective study was conducted at the Prince of Wales Hospital, Hong Kong from 1st November 2015 to 30th May 2018. Consecutive patients visiting the Orthopaedics Specialist Outpatient Clinic with symptomatic end-stage OA of the knee referred and opted for TKA as treatment are invited to participate in the study. Radiographic severity of knee OA was assessed and documented based on the Kellgren and Lawrence classification . Clinical diagnosis of knee OA was based on medical history and clinical examination of knee joints. Clinical diagnosis of sarcopenia was examined using the Asian Working Group for Sarcopenia (AWGS) algorithm after they are recruited into the study.
The estimated study sample size is 50. Sample size was calculated using G*Power 3.1.9. This calculation was based upon DXA parameter being an indicator of sarcopenia. As there are no similar previous studies, the sample size was calculated based on our pilot data of the present study comparing the DXA data measured at recruitment and after 12 months. Results showed DXA difference increased from the mean values of 5.84 to 6.02 after 12 months. Accounting for the 3.1% increase with the significant levels at 0.05 and power of 0.8 yielded a sample size of 45. Expecting a 10% withdrawal rate, a total of 50 subjects were required. Instead, researchers were able to finalise the recruitment of 58 end-stage OA knee patients upon their fulfilment of study prerequisites for this research.
The inclusion criteria are: (1) aged over 50 with end-stage knee OA; (2) scheduled for TKA; (3) agreed to given written consent and be able to comply with study assessments. Exclusion criteria include (1) history of connective tissue disorders or myositis condition; (2) previous cases of alcoholism or drug abuse; (3) breastfeeding or pregnant women; (4) presence of serious pathologies with steroid-based systematic therapy in progress or got interrupted of less than 1 month, or significant hematological disease; and (5) presence of significant cognitive impairment. The status of sarcopenia was examined by AWGS algorithm after participant enrollment into the study.
Patients demographic were recorded upon enrollment. Bodyweight and height were measured using a standard stadiometer and their Body Mass Index (BMI) was calculated (bodyweight in kg/[height in m]2). Body composition at baseline and follow-ups were measured using dual-energy X-ray absorptiometry (DXA) (Horizon, Hologic, Bedford, MA). Total appendicular skeletal muscle mass (ASM) was calculated by the sum of lean mass measured in the 4 limbs, with the operator adjusting the cut lines of the limbs as described by Heymsfield et al. Knee flexion/extension muscle strength were measured by instructing the patient to perform an active knee flexion/extension movement in a sitting position with both feet free from ground, and the hip flexed at 90 degree and knee joint in mid-flexion range. The optimal isometric force of the knee flexion/extension movement is measured by the dynamometer attached at the malleoli level with a strap. The measurements were taken at maximum force for three times. Grip strength was measured as the average of 3 repeated grip measurement on a dynamometer using the dominant hand. The six-meter gait speed test was used to measure gait speed by using the best time in seconds to finish a 6-m walk along a straight line using usual walking speed and the average value was used for analysis.
Definition of Sarcopenia
Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) algorithm. A person who has low muscle mass, low muscle strength, and/or low physical performance was categorized as having sarcopenia. Low muscle mass was defined as height-adjusted muscle mass by DXA <7.0 kg/m2 for men and <5.4 kg/m2 for women; low muscle strength was defined as grip strength <28 kg for men and <18 kg for women; and low physical performance as gait speed <1.0 m/s for both men and women.
Assessments were consecutively conducted within one month before TKA (baseline), 6 months (post-treatment), and 12 months postoperatively. Primary outcomes were regularly examined via handgrip (handgrip dynamometer at upper extremity strength), lower limb muscle strength in terms of knee joints flexion/extension and 6-meter gait speed test at lower extremity functions. DXA measurement values were used to produce the Lean Mass Index (LMI) which is defined as the ratio of total lean mass (soft tissue only, excluding bone) to height-squared and the Appendage Lean Mass Index (ALMI) which is defined as the ratio of lean mass on limbs to height-squared.
Secondary outcomes were measured by Quality of Life (QOL) measurements in psychological and physical health. Pain, stiffness and physical functions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) indicated scores ranging from zero to 100, with higher scores representing greater associable disability functions. Medical Outcomes Study Short Form 12 Health Survey Version 2 (SF-12v2) were administered to approximate the general health status in subjects as means to compute a Physical and Mental Health Composite Score (PCS & MCS) that range from a scale of zero to 100, indicated by the higher the score the better level of health. International Physical Activity Questionnaire (IPAQ) instructed an internationally comparable record of health-related physical activity, used to monitor changes of the amount or types of exercise performance level over the research period. Physical activity levels in terms of IPAQ were categorised as "low", "moderate" and "high" and the categorization followed the standard criteria[32, 33]. The contraposition of SF-12v2 and IPAQ indexes across research timelines allowed meaningful interpretation of bodily and psychological functional fluctuation over the effect of TKA on sarcopenia symptom.
Demographic statistics on age, sex, BMI, and length of hospital stay were reported in terms of mean ± SD or frequencies where appropriate (Table 1). Comparisons of ALMI and LMI against patients with or without sarcopenia were carried out both cross-sectionally (between patients with sarcopenia or not) and longitudinally (among the 3-time points (baseline, 6 months and 12 months)) correspondingly. Longitudinal comparisons of mean values of PCS and MCS in SF12v2, WOMAC domain scores, IPAQ findings in terms of low, moderate, and high activities, knee flexion/extension strength, as well as handgrip scores and 6-meter gait speed were made. To control the possible confounders, further longitudinal comparisons were performed by controlling sex, age, and BMI using one-way ANOVA. A two-sided p-value ≤ 0.05 was considered statistically significant. All statistical analyses were carried out using IBM SPSS Version 26.0 (Armonk, NY: IBM Corp).