Long-term risk factors for, and the impact of age-related muscle loss on the musculoskeletal health of older adults

Loss of skeletal muscle mass and function with ageing is a major public health concern with substantial financial implications. This thesis aims to examine the risk factors for age-related muscle changes over 10 years and the impact that these changes have on falls risk, fracture, mortality, and health-related quality of life (HRQoL) in community-dwelling older adults. Data from a population-based sample of older adults aged 50‚-80 years (51% women; mean age 63¬±7.4 years) studied at baseline, 2.5, 5, and 10 years were analysed. Appendicular lean mass (ALM) and bone mineral density (BMD) were assessed by Dual-energy X-ray Absorptiometry (DXA). Handgrip strength (HGS) and lower-limb muscle strength (LMS) were measured using dynamometer, and muscle quality was calculated (muscle strength/muscle mass). Physical activity [steps/day] was assessed using a pedometer and the intensity of physical activity was measured using an accelerometer. Falls risk was measured using the Physiological Profile Assessment, fractures were self-reported and mortality was ascertained from the death registry. Serum 25-hydroxyvitamin D [25(OH)D] was assessed by radioimmunoassay, and HRQoL, knee pain and dysfunction were assessed using standardised questionnaires. Traditionally, analysis has focused on examining how loss of muscle mass, strength and muscle quality differ between individuals (between-person comparison). Less well recognised is how variability in risk factors over time within the same individual (within-person comparison) are associated with muscle loss. The first study of this thesis described the longitudinal associations of between-person and a dynamic within-person variability in serum 25(OH)D, physical activity and knee pain and dysfunction with muscle mass, strength and muscle quality over 10 years. Both between-person and within-person increases in physical activity were associated with a higher muscle mass, strength and muscle quality. Within-person and between-person increases in knee pain and dysfunction were associated with a lower muscle strength and quality but not muscle mass. Between-person effects showed that higher average 25(OH)D was associated with higher 10-year average muscle mass, strength and muscle quality; whereas, within person increases in 25(OH)D was associated with a higher muscle strength and quality but not muscle mass. The second study compared the performance of low muscle mass, muscle strength and muscle quality assessed at baseline with falls risk, incident fracture and mortality over 10 years. All baseline muscle strength and muscle quality measures were significantly associated with higher falls risk score at 10 years. Low handgrip and ALM/body mass index (BMI) were the only significant predictors of fracture and mortality respectively. The third study described the longitudinal association of between-person and within-person variability in serum 25(OH)D, physical activity, knee pain and dysfunction with falls risk over 10 years. Knee pain and dysfunction above an individual's usual level of pain increases the risk of falling, whereas, increasing one's own moderate-to-vigorous physical activity level further reduced their risk of falling. Between-person but not within-person associations were observed between 25(OH)D and falls risk. The fourth study examined the associations between low muscle mass, upper- and lower-limb muscle strength with HRQoL over 10 years. Participants with low LMS and low HGS (in women only) at baseline had a clinically meaningful difference in 10-year HRQoL compared to those with normal strength. There was a weaker but still significant association between low muscle mass and 10-year HRQoL. The final study described the relationship between low muscle mass or strength, in the presence of osteopenia, with fracture and mortality risk. Incident fracture risk was significantly higher in participants with both osteopenia and dynapenia (osteodynapenia) compared to those without dynapenia or osteopenia. Mortality risk was significantly higher in participants with both osteopenia and sarcopenia (osteosarcopenia) compared to those without sarcopenia or osteopenia. However, osteosarcopenia and osteodynapenia did not lead to a significantly greater fracture or mortality risk compared to having these conditions on their own. In conclusions, in addition to traditional between-person associations, variability in physical activity, 25(OH)D, knee pain and dysfunction within an individual over time relate to muscle changes and falls risk. Within-person effects were generally weaker compared to between-person estimates. Furthermore, muscle strength, which can be easily measured in clinical practice, appears more important than muscle mass for identifying individuals with a higher falls risk, fractures and poorer quality of life. However, muscle mass appears to be a better predictor of mortality risk. Low BMD combined with low muscle mass or strength does not significantly increase the risk of fracture or mortality compared to having low BMD or low muscle mass/strength alone, suggesting that combined assessments may not add additional risk for fracture and mortality.