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). The study was registered with 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 were 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 were: (1) aged over 50 years with end-stage knee OA; (2) scheduled for TKA; (3) agreed to provide written consent and able to comply with study assessments. Exclusion criteria were: (1) history of connective tissue disorders or myositis; (2) previous period of alcoholism or drug abuse; (3) breastfeeding or pregnant women; (4) presence of serious pathologies with steroid-based systematic therapy in progress or interrupted for less than one month, or significant haematological disease; and (5) presence of significant cognitive impairment. The sarcopenia status was assessed by the AWGS algorithm after participant enrolment into the study.
Patient demographic data were recorded upon enrolment. Body weight and height were measured using a standard stadiometer and the body mass index (BMI) was calculated (bodyweight in kg/[height in m]2). Body composition at baseline and follow-up was 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 four 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 off the ground, and the hip flexed at 90° and the knee joint in the mid-flexion range. The optimal isometric force of the knee flexion/extension movement was measured by a 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 three repeated grip measurements 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 categorised 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.
The primary outcome was DXA measurements. DXA 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 the limbs to height squared.
Several measurements comprised the secondary outcomes and assessments were consecutively conducted within one month before TKA (baseline), 6 months (post-treatment), and 12 months postoperatively. Quality of life (QOL) measurements were done in terms of psychological and physical health. Pain, stiffness and physical functions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were given 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) was administered to approximate the general health status in subjects as a means to compute a physical and mental health composite score (PCS & MCS) ranging from zero to 100; a higher score indicates a better level of health. The International Physical Activity Questionnaire (IPAQ) is an internationally comparable record of health-related physical activity, used to monitor changes in the amount or type of exercise performance level over the research period. Physical activity levels in terms of IPAQ were categorised as “low”, “moderate” and “high” and the categorisation followed the standard criteria [32, 33]. The contraposition of SF-12v2 and IPAQ indexes across research timelines allowed for a meaningful interpretation of bodily and psychological functional fluctuations to assess the effect of TKA on sarcopenia symptoms. Handgrip (handgrip dynamometer at upper extremity strength), lower limb muscle strength in terms of knee joint flexion/extension and the 6-m gait speed test for lower extremity function were also recorded at the three time points.
Demographic statistics on age, sex, BMI and length of hospital stay are 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 three time points, i.e. 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-m gait speed were made. To control for 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).