Abstract
Frailty in older people is associated with a vulnerability to adverse events. While ageing is associated with a loss of physiological reserves, identifying those with the syndrome of frailty has the potential to assist clinicians to tailor treatments to those at the risk of future decline into disability with an increased risk of complications, morbidity and mortality. Sarcopenia is a key component of the frailty syndrome and on its own puts older people at risk of fragility fractures; however, the clinical syndrome of frailty affects the musculoskeletal and non-musculoskeletal systems. Hip fractures are becoming a prototype condition in the study of frailty. Following a hip fracture, many of the interventions are focused on limiting mobility disability and restoring independence with activities of daily living, but there are multiple factors to be addressed including osteoporosis, sarcopenia, delirium and weight loss. Established techniques of geriatric evaluation and management allow systematic assessment and intervention on multiple components by multidisciplinary teams and deliver the best outcomes. Using the concept of frailty to identify older people with musculoskeletal problems as being at the risk of a poor outcome assists in treatment planning and is likely to become more important as effective pharmacological treatments for sarcopenia emerge.
This review will focus on the concept of frailty and its relationship with functional decline, as well as describing its causes, prevalence, risk factors, potential clinical applications and treatment strategies.
Many of the common musculoskeletal problems of old age including osteoporosis, osteoarthritis and fragility fractures are associated with mobility disability and can spiral into functional decline and disability. As the population ages and patients present with more and more co-morbidities, it is important for clinicians to be able to identify quickly those who require resource-intensive multi-component interventions delivered by teams from those who require a short physiotherapy program or a self-management program. The presence of frailty is starting to guide treatment for health conditions in older people because it has been shown that frailty can predict the response to treatment and the likelihood of adverse complications .
Frailty is a term first used in the medical literature in the 1970s, which is receiving increasing focus in research and clinical practice due to its ability to predict poor outcomes in older people of relevance to society such as falls, disability, functional decline, hospitalisation, institutionalisation and mortality . While linked to theories of ageing, it has come to be thought of as a separate condition indicating abnormal ageing and poor health and therefore a potential target for interventions and therapies to slow or reverse its progression . In addition, it is known to occur in tandem with other clinical conditions of ageing including sarcopenia, functional decline, neuroendocrine disorders and immune dysfunction .
Frailty has been associated with an increased risk of having a fall (odds ratio (OR) 2.02, 95% confidence interval (CI) 11.44–2.83) and experiencing a greater number of fractures in community-dwelling older adults (OR 3.67, 95% CI 1.47–9.15) . The costs to the US of fragility fractures seen in frail older adults such as hip fracture has been estimated to be >$US 12 billion per year . The costs of providing hospital, medical and community services for frail older adults compared to non-frail older adults have been estimated to be up to an additional ₤109 per week in the UK . Therefore, while the debate continues regarding the identification and aetiology of frailty, the importance of developing adequate means of addressing this increasing burden on the health-care system cannot be overestimated.
Definitions of frailty
The recent push to standardise definitions of frailty has resulted in a number of reviews of this topic published recently . Two models of frailty dominate the literature. Fried et al. have proposed a phenotype model of frailty that evolved from factors such as chronic disease, and musculoskeletal changes, leading to reduced physical activity and energy expenditure, abnormalities in neuroendocrine regulation and chronic under-nutrition. The consequences of the above conditions include loss of weight and muscle mass which further impact upon musculoskeletal changes producing the cyclical nature of the model. Based upon this model, Fried proposed five criteria for use in research and clinical settings including unintentional weight loss or loss of muscle mass (i.e., sarcopenia), weakness, poor endurance or exhaustion, slowness and low activity levels. From this phenotype, a practical instrument for assessing performance in these areas based on five measures included in the Cardiovascular Health Study has been created . This phenotype was validated with 5317 participants aged ≥65 years and was associated with an increased risk of mortality (hazard ratio (HR) = 6.47, 95% CI 4.63–9.03, p < 0.0001), first hospitalisation (HR 2.25, 95% CI 1.94–2.62, p < 0.0001), first fall (HR 2.06, 95% CI 1.64–2.59, p < 0.0001), increasing activities of daily living (ADL) disability (HR 5.61, 95% CI 4.50–7.00, p < 0.0001) and worsening mobility (HR 2.68, 95% CI 2.26–3.18, p < 0.0001) over 3 years of follow-up . Since that study, these criteria or similar have been shown to be associated with an increased risk of mortality, admission to residential aged care, hospitalisation, declining ability to perform ADLs and instrumental ADLs, risk of falls and declining mobility in community-dwelling older adult populations of both men and women .
The other important model was developed by Rockwood et al. and is often described as the accumulation model. It takes into account the interplay between ‘assets’ or components, which help an older person to remain living in the community and ‘deficits’ or components which are detrimental to their ability to live independently. These include biomedical factors (such as health, illness and disability) as well as psychosocial factors (such as dependence on others and resources available). Accordingly, it is this balance between the assets and the deficits which will determine whether someone is able to remain in the community or not – if the deficits outweigh the assets for an individual, they will not be able to maintain their position in the community and require institutional input. This theory has seen the development of instruments for assessing the degree of frailty in individuals or populations, commonly referred to as frailty indexes. For a deficit to be considered to contribute to frailty it must be acquired, related to health status, and increase with age but not so rapidly that saturation is reached at a relatively young age limiting the specificity of the index . Commonly, the frailty indexes list >70 potential deficits including aspects of general health and disease status, ability in ADLs and psychological symptoms. A 92-item version validated in 1468 participants from a general population sample (Canadian Study of Health and Aging) found an association with time to death and increasing frailty index score ( r = −0.234, p < 0.0001) which was greater than that seen between time to death and increasing age ( r = −0.088, p < 0.05), highlighting the usefulness of the concept of frailty above that of age to predict adverse outcomes. Similarly, Evans et al. found an association between frailty measured by a shorter 55-item frailty index and mortality in a smaller sample ( n = 752) of older adults admitted to an acute care setting over 5 years (HR 1.05, 95% CI 1.04–1.07) . Velanovich et al. found a significant increase in the risk of mortality with each unit increase in frailty measured using an 11-item index in a range of surgical inpatient admissions ( p < 0.0001). For orthopaedic surgical admissions, the OR of mortality for each unit increase in frailty ranged from 3.36 (95% CI 2.64–4.27) to 11.68 (95% CI 7.81–17.46), dependent on the complexity of the operation. Therefore, a wide range of frailty indexes have predictive validity, providing evidence for the accumulated deficit models of frailty.
Development of frailty
There has been much debate on the factors that contribute to the pathogenesis of frailty, due in part to the variety in definitions of frailty in the literature, and current models often include psychosocial as well as physical components . Nevertheless, physical decline and disability remains one of the key predictive features in the development of frailty and therefore musculoskeletal conditions are important considerations . An overview of some of the interrelated factors promoting the development of the frailty syndrome and its consequences are illustrated in Fig. 1 .
A key cause of frailty and physical decline in older adults is sarcopenia . Sarcopenia (from the Greek words sarx meaning flesh and penia or poverty) refers to the loss of muscle mass associated with ageing, but recent definitions include aspects of reduction in mobility and reduction in appendicular lean mass . Sarcopenia has been found to be an independent predictor of physical disability and development of mobility disorders, as well as reduced bone mineral density (BMD) . Diagnosis is usually through identifying the loss of lean body mass (e.g., <20th percentile for young healthy adults ), although it is important to note that muscle strength is not always correlated to total lean mass . Therefore a measurement of physical performance and muscle function is required, such as a reduced mobility or gait speed (e.g., gait speed <1 m/s) . Sarcopenia itself is a multi-system syndrome brought on by a number of interrelated factors , including an increasing inflammatory state, reducing protein synthesis and promoting apoptosis, reduced growth hormone, testosterone and insulin-like growth factor-1 (IGF-1) reducing muscle growth and muscle strength and disorders in the nervous system control of muscular function. In addition, anorexia and malnutrition promotes loss of weight and muscle mass. A key factor promoting all these dysfunctions is immobility and lack of exercise, which is a driving factor behind most of these physical and immunologic changes, and promoting the cyclical decline seen in the condition, as illustrated in Fig. 1 . While traditionally associated with a low body mass, sarcopenia is increasingly being identified in obese individuals which results from the substitution of muscle mass for fat mass and related immobility and lack of use of muscular systems . A relationship is seen between frailty and low or very high BMI, with rates lowest in those with a body mass index (BMI) between 20 and 29.9 . In addition, a relationship is seen between high waist circumference (defined as >88 cm in women and >102 cm in men) and increased frailty .
Chronic low-level inflammation has also been proposed as a causative factor , which plays a key role in both the ageing process and the development of both sarcopenia and frailty . A number of the signs and symptoms of frailty (low muscle strength, exhaustion and unintentional weight loss) are also seen with increased pro-inflammatory markers, especially IL-6 . The potential pathologic causes of chronic low-level inflammation proposed include persistent infection with the herpes virus cytomegalovirus (CMV) . In addition, other chronic diseases such as atherosclerosis, Alzheimer’s disease, cancer and autoimmune diseases have been shown to contribute to inflammatory status and frailty .
Development of frailty
There has been much debate on the factors that contribute to the pathogenesis of frailty, due in part to the variety in definitions of frailty in the literature, and current models often include psychosocial as well as physical components . Nevertheless, physical decline and disability remains one of the key predictive features in the development of frailty and therefore musculoskeletal conditions are important considerations . An overview of some of the interrelated factors promoting the development of the frailty syndrome and its consequences are illustrated in Fig. 1 .
A key cause of frailty and physical decline in older adults is sarcopenia . Sarcopenia (from the Greek words sarx meaning flesh and penia or poverty) refers to the loss of muscle mass associated with ageing, but recent definitions include aspects of reduction in mobility and reduction in appendicular lean mass . Sarcopenia has been found to be an independent predictor of physical disability and development of mobility disorders, as well as reduced bone mineral density (BMD) . Diagnosis is usually through identifying the loss of lean body mass (e.g., <20th percentile for young healthy adults ), although it is important to note that muscle strength is not always correlated to total lean mass . Therefore a measurement of physical performance and muscle function is required, such as a reduced mobility or gait speed (e.g., gait speed <1 m/s) . Sarcopenia itself is a multi-system syndrome brought on by a number of interrelated factors , including an increasing inflammatory state, reducing protein synthesis and promoting apoptosis, reduced growth hormone, testosterone and insulin-like growth factor-1 (IGF-1) reducing muscle growth and muscle strength and disorders in the nervous system control of muscular function. In addition, anorexia and malnutrition promotes loss of weight and muscle mass. A key factor promoting all these dysfunctions is immobility and lack of exercise, which is a driving factor behind most of these physical and immunologic changes, and promoting the cyclical decline seen in the condition, as illustrated in Fig. 1 . While traditionally associated with a low body mass, sarcopenia is increasingly being identified in obese individuals which results from the substitution of muscle mass for fat mass and related immobility and lack of use of muscular systems . A relationship is seen between frailty and low or very high BMI, with rates lowest in those with a body mass index (BMI) between 20 and 29.9 . In addition, a relationship is seen between high waist circumference (defined as >88 cm in women and >102 cm in men) and increased frailty .
Chronic low-level inflammation has also been proposed as a causative factor , which plays a key role in both the ageing process and the development of both sarcopenia and frailty . A number of the signs and symptoms of frailty (low muscle strength, exhaustion and unintentional weight loss) are also seen with increased pro-inflammatory markers, especially IL-6 . The potential pathologic causes of chronic low-level inflammation proposed include persistent infection with the herpes virus cytomegalovirus (CMV) . In addition, other chronic diseases such as atherosclerosis, Alzheimer’s disease, cancer and autoimmune diseases have been shown to contribute to inflammatory status and frailty .
Functional decline and its role in frailty
There is growing evidence that the development of functional limitations is such that problems with mobility are one of the first markers for frailty . While disability and functional limitations have been identified as being highly correlated with frailty, the concept is now regarded as distinct to that of frailty, but sharing many common pathways for development . Functional decline or disability is usually described as a loss of an individual’s ability to perform basic tasks required to maintain independence in living status (usually described as ADLs) . Basic ADLs include everyday tasks such as bathing, dressing, feeding, continence, toileting and mobility . Instrumental ADLs require higher-level function and include tasks such as banking, shopping and driving . Measuring functional decline is of interest, similarly to the concept of frailty, for its ability to predict future mortality, morbidity, hospitalisation and institutionalisation . An increased risk is associated with cognitive impairment, hospitalisation, poly-pharmacy, older age, history of fractures, malnutrition, low physical activity, lower strength and depression . Musculoskeletal conditions have long been recognised as a major cause of functional impairment and disability. The total number of disability-adjusted life years associated with musculoskeletal conditions worldwide has been estimated to be >30,000,000, and they remain one of the ten leading causes of disability worldwide. In a recent study in France, over a quarter of the population reported at least one musculoskeletal condition, with osteoarthritis and lower back pain being the most commonly reported disorders . Disability was common among those with rheumatic and musculoskeletal conditions, with up to 22% of those with osteoarthritis and inflammatory arthritis experiencing difficulty mobilising compared with only 5% of those without the conditions. Participants with musculoskeletal and rheumatic conditions also commonly experienced impairments in most basic functional activities, including shopping, doing housework and carrying objects, and needed more assistance from family and health professionals, and there is evidence of increasing decline over time . Particular risk factors for decline in arthritis sufferers include pain, reduced muscle strength and joint instability, range of joint movement, co-morbidities including cardiovascular conditions, diabetes and stroke, high body weight, avoidance of exercise and female gender, factors which are also commonly identified in the aetiology of frailty .
An increasingly important contributor to the burden of musculoskeletal conditions is fragility fractures. Worldwide, there were >5.2 million non-traumatic fractures in 2010 with over half of those attributable to fractures of the hip and spine . A recent review has highlighted the devastating effect of hip fractures on the long-term function of older adults, with 29% of cases not regaining their pre-fracture level of function in ADL . Over 40% of patients had not regained their pre-fracture level of mobility at 1 year following fracture, and over a third were unable to walk independently due to the fractures. In addition, ongoing pain is widespread in this population, with 47% reporting pain ≥1 years following the fracture. This widespread pain and difficulty mobilising are likely markers for overall decreasing physical exercise and function, which are independently associated with frailty. As a result of this widespread functional decline, a large proportion will become increasingly dependent on community and residential care services so any identification of reversible components will impact not just on individuals but on the community as well.
How is frailty identified or diagnosed?
Given the rapid ageing of the population, the creation of tools to identify frail older people has received increasing focus over the past decades . Recent recommendations suggest that all persons over the age of 70 should be screened for frailty and, in addition, persons of any age where significant weight loss (≥5% of total body weight) occurs unplanned and as a result of chronic disease . In addition, low physical activity and functional decline suggest problems, and older adults with musculoskeletal conditions should be screened. Screening should ideally occur early, before significant dependence in basic ADLs has developed, to develop treatment plans to prevent further or reverse decline and plan for future increased health and social support . There are currently many simple rapid screening tools available that are validated in older adult populations (see Table 1 ) . These tools are designed to be quickly administered and based mostly on self-report of the patient, although the Cardiovascular Health Study Frailty Screening Scale and Gérontopôle Frailty Screening Tool require performance-based measures such as gait speed and grip strength, which may pose challenges dependent on access to relevant space and equipment in a clinical setting. In addition, the Clinical Frailty Scale and Gérontopôle Frailty Screening Tool require clinical judgement in their scoring systems, requiring a degree of experience and knowledge to be used effectively .
| Instrument/study | Characteristics | Scoring |
|---|---|---|
| Simple ‘FRAIL’ Questionnaire Screening Tool | 5-Item self-report questionnaire focussing on: fatigue, aerobic fitness and strength, presence of co-morbidities and weight loss | Meeting ≥3 criteria = frail Meeting 1 or 2 criteria = pre-frail |
| Cardiovascular Health Study Frailty Screening Scale | 5-Item questionnaire with mixture of self-report and performance measures focussing on: weight loss, exhaustion, low activity levels, slowness in mobility and weakness in grip strength | Meeting ≥3 criteria = frail Meeting 1 or 2 criteria = pre-frail |
| Clinical Frailty Scale | 9-Item descriptive scale providing criteria for classifying people based on aspects of their fitness, general health, activity level, independence, mobility, level of co-morbidity, frailty | Clinical judgement |
| Gérontopôle Frailty Screening Tool | 6-Item questionnaire based on clinical opinion of physician focussing on: living status, weight loss, fatigue, mobility and memory, plus an overall assessment | Clinical judgement |
In addition to the four rapid screening tools highlighted above, there are >30 different tools published for the identification of those at risk of frailty, ranging from single outcome measures to large multi-component assessment instruments . A number of reviews have been published outlining the variety of instruments available and their validity . While a large variety of tools to assess frailty in populations exist, there are two main groups . One includes either single- or multi-component assessments of physical ability, whereas the other considers a combination of physical, social, cognitive and other factors in the identification and assessment of frailty . A recent review focused on instruments to assess frailty for use in measuring outcomes in clinical practice and research, with a view to promoting interventions to prevent or manage frailty in practice . de Vries et al. identified 20 different instruments (see Table 2 ) and assessed their clinimetric properties by assessing content validity, internal consistency, construct validity, agreement, reliability, responsiveness and interpretability. They subscribed to current multidimensional models of frailty, which consider impairments in multiple domains of the individual as contributing to frailty, including physical, psychological and social domains, and assessed the instruments’ coverage of all of these areas. They found that only five instruments included items on all three of these frailty domains: the frailty index (FI) or accumulated deficits model , Groningen Frailty Indicator (GFI) , Clinical Global Impression of Change in Physical Frailty (CGIC-PF) , Geriatric Functional Evaluation (GFE) and the Geriatric Functional Evaluation Frailty Index-Comprehensive Geriatric Assessment (FI-CGA) . In addition, the majority of the instruments utilised a dichotomous scoring system (i.e., frail vs. not frail), which gives minimal relevance for measuring the change in populations over time . Other instruments either utilise multiple levels of frailty or use continuous or ordinal scoring scales , which may be more relevant to clinicians wanting to determine the level of frailty in one patient compared to another, or change in the level of frailty over time.
| Instrument/study | Characteristics | Scoring | Measurement of mobility | Measurement of strength |
|---|---|---|---|---|
| Evaluative frailty index for physical activity (EFIP) | 50-Item frailty index. Self-report questionnaire | Total score divided by the total number of questions (50). Range 0–1 with greater score indicating greater frailty | Assistance in transfers, assistance with mobility | – |
| Physical frailty phenotype (PFP), mental frailty phenotype (MFP) and social frailty phenotype (SFP) | 18-Item mixture of self-report and physical performance measures and common geriatric assessment tools | Greater or equal than 2 criteria in the SFP and MFP and greater or equal than 4 criteria in the PFP | – | – |
| Tilburg Frailty Indicator (TFI) | 25-Item self-report questionnaire | Higher score indicating greater frailty | Difficulty in mobility | Self-report poor grip strength |
| Frailty phenotype | 5-Item self-report questionnaire | Those meeting ≥3 criteria were categorised as frail, those meeting 1–2 criteria as pre-frail, those meeting none of the criteria as robust | Walking speed | Grip strength |
| Frailty index, accumulation of deficits | A index of at least 40 deficits including a mix of self-report and physical assessment and examination | Total score divided by the total number of questions. Range 0–1 with greater score indicating greater frailty | Timed up and go (TUG) test | Physical examination |
| Modified Functional Independence Measure (FIM) | 18-Item self-report questionnaire | Range from 7 to 49 with higher score indicating greater frailty. | Transfers | – |
| Carriere Instrument | Combination of self-report and performance tests | Score from 25 to 165 which is transformed on to a scale of 0–1. Larger scores indicate greater risk of future dependency. | Chair stand test, gait speed, step length, foot tapping | Grip and quadriceps strength, calf circumference |
| ‘Gealey’ Instrument | 13-Item self-report questionnaire | Score from 0 to 24, greater score indicate greater dependency. | Walking, transfers | – |
| Groningen Frailty Indicator (GFI) | 15-Item self-report questionnaire | Score ranging from 0 to 15, score of 4 or higher represents moderate to severe frailty. | Walking (self-report) | – |
| Frail Elderly Functional Assessment Questionnaire | 19-Item self-report questionnaire | Score ranging from 0 to 55, with higher score indicating greater frailty | Walking, transfers (self-report) | – |
| ‘Guilley’ Instrument | 17-Item self-report questionnaire divided into five domains (sensory, mobility, physical pains, memory, energy) | Scoring of each item range from 0 to 3. Score of 3 or higher for one item in the domains physical pains, memory and energy, or 2 or higher for one item in the sensory and mobility domains. | Walking | – |
| ‘Rothman’ Instrument | 7-Item questionnaire including self-report and physical performance measures | Those meeting ≥3 criteria were categorised as frail, those meeting 1–2 criteria as pre-frail, those meeting none of the criteria as robust | Gait speed | – |
| Clinical Global Impression of Change in Physical Frailty (CGIC-PF) | 13-Item instrument for use during geriatric assessment | Scores ranging from 1 to 7 with lower scores indicating greater decline in physical frailty | Walking, transfers, stairs, use of assistive devices, | Grip strength, chair stand, manual muscle tests |
| The Vulnerable Elders Survey (VES) | 13-Item self-report questionnaire | Scores ranging from 0 to 10, higher scores indicate greater frailty | Walking | Lifting 10 lbs (self-report) |
| Study of Osteoporotic Fractures (SOF) instrument | 3 Item questionnaire using a mixture of self-report and physical testing | Those meeting ≥2 criteria were categorised as frail, those meeting 1 criteria as pre-frail, those meeting none of the criteria as robust | – | Chair stand |
| ‘Chin A Paw’ Instrument | 2-Item self-report questionnaire | Those meeting the 2 criteria classified as frail | – | – |
| ‘Puts’ Instrument | 9-Item questionnaire combination of self-report and physical performance tests | Score ranging between 0 and 9, those meeting ≥3 criteria classified as frail. | – | – |
| Ravaglia Instrument | 9-Item questionnaire combination of self-report and physical performance tests | Score ranging from 0 to 9 with greater score indicating greater risk of mortality | Tinetti gait and balance scale | – |
| Winograd Instrument | 15-Item criteria covering co-morbidities, physical and mental health, impairments and social factors | Score for frailty | Impaired mobility | – |
| Grip strength | Measurement of grip strength | Reduced grip strength indicating greater frailty | – | Grip strength |
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Determinants of MSK health and disability – Social determinants of inequities in MSK health
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Corrigendum to “Granulomatous inflammation: the overlap of immune deficiency and inflammation” [Best Pract Res Clin Rheumatol 28 (2014) 191–212]
‘Erratum to “Osteoporosis and fragility fractures: Vertebral fractures” [Best Practice & Research Clinical Rheumatology 27 (2013) 743–55]’
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