Introduction

Sarcopenia (SP), osteoporosis (OP), and frailty are highly prevalent in older adults but are frequently under-recognized. They have all been shown to have an adverse impact on quality of life and are associated with disability and mortality.1 United Nations estimations showed that in 2010 there were 524 million people in the world aged 65 years old and over, with projections indicating that this number will increase to 1.5 billion by 2050 (a three-fold increase).2 Hence, identification of individuals who might be particularly vulnerable to the adverse outcomes of musculoskeletal ageing is of clinical and public health concern.

Sarcopenia is characterized by progressive and generalized decline in muscle strength, function, and muscle mass with increasing age or secondary to a disease process. SP increases the likelihood of falls and adversely impacts on functional independence and quality of life.3, 4 OP, the commonest metabolic bone disease in older people, is characterized by both low bone mass and microarchitectural deterioration that predisposes to low-energy transfer fragility fractures. These are associated with chronic pain, impaired physical function, loss of independence, and a higher risk of short-term and longer-term institutionalization.5 Consequently, both these conditions confer a high health burden for the individual as well as health care systems. ‘Osteosarcopenia’ is the term given when OP and SP occur in consort and recent intense focus has been on their combined effects on current and future health.

The syndrome of frailty is associated with, but not an inevitable consequence of ageing and is characterized by a vulnerability to stressor events that can be both internal and external.6 Both frailty and pre-frailty, the prodromal state before the onset of clinically identifiable frailty, are associated with adverse outcomes.7 The most widely used definitions of physical frailty are the phenotype model described by Fried, where frailty is identified by the presence of at least three out of five physical characteristics: weight loss, exhaustion, low energy expenditure, slow walking speed, and low handgrip strength.8 The cumulative deficit model of frailty described by Rockwood et al. also predicts adverse health outcomes and comprises age-associated accumulation of deficits that range from symptoms, sensory deficits, clinical signs, diseases, disabilities, and abnormal laboratory test results.9

Few other studies have considered interrelationships between SP, OP, and frailty. For example, participants with SP were reported to have a high incidence of OP, a higher incidence of falls and fractures,10, 19, 11 but in these analyses frailty was not considered the outcome. For instance, patients with SP had 12.9 times higher odds of having OP and 2.7 times higher odds of having fractures than the non-sarcopenic ones in a population-based Finnish study,20 and similarly, bone mineral density (BMD) was found to be lower in sarcopenic individuals in the Copenhagen Sarcopenia study, increasing the risk of having OP.21 Older males with a diagnosis of probable and definite SP were eight times more likely to have a diagnosis of osteopenia or OP,22 where in postmenopausal Brazilian women, SP and severe SP was shown to impose a higher risk for OP adding to the growing evidence that SP and OP frequently co-occur.23

However, studies that have considered frailty as an outcome suggest that the risks of serious morbidity are notably higher when OP and SP coexist.24, 26 Individuals with osteosarcopenia have also increasingly higher risk of mortality compared with those with SP or OP alone.27

Given that ageing is commonly associated with SP and OP, the aims of this study were (1) to explore associations between SP and OP, individually or in combination, with frailty in community-dwelling older adults participating in the Hertfordshire Cohort Study (HCS), and (2) to determine if coexistence of both SP and OP (osteosarcopenia) carries a higher likelihood of being frail. Given the importance of multimorbidity on health outcomes,28 and the association that previously has been described between osteosarcopenia and chronic diseases,29 we also considered (3) whether the coexistence of SP and OP was associated with a significantly heavier health burden, as assessed by the number of concurrent long-term conditions. The wealth of phenotypic information collected in the HCS, a cohort study of community-dwelling older adults, has allowed us to describe the prevalence and pre-frailty in this group and to consider whether the coexistence of SP and OP in individuals interacted to amplitude risk of frailty. This is of high clinical relevance as the identification of coexistent SP and OP coexistence not only allows early treatment and management strategies but might also offer an opportunity to mitigate frailty risk.5, 6

Methods Study participants

The HCS was designed to examine the relationship between growth in infancy and the subsequent risk of common adult diseases, including OP and SP, and has been described in detail elsewhere.30 Participants have been followed up at a number of time points since its inception. The present study was performed using baseline data collected in 2011. All study participants provided written informed consent, and ethical approval was obtained from the Hertfordshire Research Ethics Committee. All participants gave written informed consent.

Data collection Questionnaire and anthropometry

Participants completed questionnaires that comprised questions related to lifestyle including smoking habits, alcohol consumption, physical activity (LASA Physical Activity Questionnaire—LAPAQ), and nutrition (Short Food Frequency Questionnaire—FFQ). Anthropometric measurements including height and weight were measured to calculate body mass index (BMI).

Physical performance and muscle mass

Grip strength was measured three times in each hand using a Jamar hand-held isokinetic dynamometer using a standardized protocol.31 The maximum value was used in analyses. Gait speed (metres per second) determined after timed 8 foot walk test. The use of assistive devices was permitted, if required. For chair rises (also used to assess for physical function), the time taken for participants to stand up and sit down again (with their arms crossed across their chest) a total of five times was recorded.

Skeletal muscle mass was measured with a body composition dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy Advanced) to quantify regional as well as total lean mass, fat mass, and bone mineral content. Proximal femur BMD values were determined using standard DXA.

Definitions of sarcopenia, osteoporosis, frailty, and comorbidity Sarcopenia

Sarcopenia was defined using the revised EWSGOP2 criteria for low muscle strength measured by hand grip strength (<27 kg in men and <16 kg in women) or slow chair rise time (>15 s for five rises) and low muscle quantity [appendicular skeletal mass (ASM) index (ASM/height2) < 7.0 kg/m2 in men and <5.5 kg/m2 in women].32

Osteoporosis

Osteoporosis was defined according to the World Health Organization criteria and diagnosed when BMD T-scores were lower than the peak bone mass by 2.5 SD at the femoral neck or the use of osteoporotic treatment including hormone replacement therapy (HRT), bisphosphonates, or raloxifene was reported.

Frailty

Frailty was defined using the standard Fried definition using similar cut-offs for muscle strength that were used to define SP (grip strength <27 kg in men and <16 kg in women) in addition to the presence of unintentional weight loss, self-reported exhaustion, and lowest sex-specific fifth of activity time: 0 out of 5 domains = non-frail, 1 or 2 domains = pre-frail, and ≥3 domains = frail. The presence of unintentional weight loss was defined as a positive answer to the question: ‘In the last year, have you lost more than 10 pounds (4.5 kg) unintentionally (i.e. not due to dieting or exercise)?’. The presence of self-reported exhaustion was defined as an answer of a moderate amount of time or most of the time (i.e. ≥3 days) to the question: How often in the last week did you feel ‘everything I did was an effort’ or ‘I could not get going’.

Comorbidity

Participants were asked to self-report their comorbidities with the use of a questionnaire. We then categorized the number as none, one, two, and three or more. Multimorbidity was defined when participants self-reported three or more comorbidities.

Statistical analysis

Descriptive statistics for continuous variables were expressed as mean and standard deviation (SD) or median and interquartile range (IQR) as appropriate. Categorical variables were expressed as frequency (N) and percentage (%). Differences between groups (such as frailty status) were assessed using analysis of variance (ANOVA), Kruskal–Wallis tests, Pearson's χ2 tests, or Fisher's exact tests as appropriate. Logistic regressions were performed to analyse associations of OP at femoral neck, SP, and coexistence of OP and SP as explanatory variables for frailty adjusting for sex only initially, then further adjusting for age, BMI, current smoker, and alcohol consumption.

Results

Complete baseline data were available for 405 participants (199 men and 206 women). The median (SD) age of participants at baseline was 75.5 (73.4–77.92) years. The characteristics of this population are shown in Table 1; 4.5% of men and 2.9% of women were current smokers with no sex difference (P = 0.391). There was a significant difference between women and men at baseline in the median (IQR) alcohol consumption [men: 6.2 (1.0–12.3) units per week; women: 0.3 (0.0–3.1) units per week; P < 0.001]. Over half of participants reported to have low walking speed (≤0.8 m/s) (55.2%, 217/393) and one-fifth of them had low physical activity (80/394). One-fifth of participants had evidence of OP and 8% had evidence of SP; 20.5% (83/405) self-reported three or more comorbidities.

Table 1. Baseline characteristics of all participants All participants N Median IQR Age (years) 405 75.5 73.4–77.9 Weight (kg) 405 76.0 68.2–85.8 BMI (kg/m2) 402 27.4 25.1–30.9 Alcohol consumption (units per week) 405 2.0 0.1–8.3 Activity time in the last 2 weeks (min/day) 394 190 124–283 N Mean SD Height (cm) 402 165.7 9.3 Maximum grip (kg) 405 28.7 10 Gait speed (m/s) 393 0.75 0.18 ALM index (kg/m2)a 295 7.27 1.08 Femoral neck BMD (g/cm2)b 306 0.889 0.139 Total N N % Female sex 405 206 50.9 Unintentional weight loss 404 16 4.0 Self-reported exhaustion 405 48 11.9 Low grip strength (<27 kg men; <16 kg women) 405 47 11.6 Low walking speed (≤0.8 m/s) 393 217 55.2 Low physical activityc 394 80 20.3 Emaciated (BMI < 18.5 kg/m2) 402 2 0.5 Current smoker 405 15 3.7 Osteoporosisd 308 66 21.4 Sarcopenia 323 26 8.0 Having 3 or more comorbidities 405 83 20.5 BMI, body mass index; IQR, interquartile range; SD, standard deviation. a ALM = appendicular lean mass. b Minimum of left and right femoral neck bone mineral density. c Low physical activity = lowest 20% of activity time. d Osteoporosis = femoral neck t-score < −2.5 or taking hormone replacement therapy, bisphosphonates, or raloxifene.

There were significant differences between non-frail, pre-frail, and frail participants with respect to age (P = 0.002), height (P = 0.035), BMI (kg/m2) (P < 0.001), alcohol consumption (P = 0.027), physical activity in the last 2 weeks (P < 0.001), walking speed (P < 0.001), and grip strength (P < 0.001) as shown in Table 2. Of the five Fried frailty components, low walking speed and low physical activity followed by self-reported exhaustion were the most prevalent (96.6%, 87.5%, and 75.8%, respectively) among frail participants.

Table 2. Characteristics of individuals by frailty category; frailty components and association with sarcopenia and osteoporosis categories Non-frail Pre-frail Frail N Median IQR N Median IQR N Median IQR P-valuea Age (years) 139 74.7 73.1–76.8 233 75.7 73.7–78.5 33 77.0 74.7–78.9 0.002* Weight (kg) 139 74.3 68.2–81.9 233 76.6 68.2–88.0 33 78.5 70.6–88.7 0.143 BMI (kg/m2) 139 26.5 24.4–29.2 230 28.4 25.6–31.2 33 29.4 25.4–32.8 <0.001* Alcohol consumption (units per week) 139 3.3 0.3–10.0 233 2.0 0.1–7.5 33 0.5 0.0–5.0 0.027* Activity time in the last 2 weeks (min/day) 139 231 178–327 223 176 107–240 32 63 42–91 <0.001* N Mean SD N Mean SD N Mean SD P-valuea Height (cm) 139 167.3 9.1 230 165.0 9.3 33 163.9 9.9 0.035* Maximum grip (kg) 139 32.4 9.3 233 27.7 9.5 33 20.6 10.1 <0.001* Gait speed (m/s) 139 0.90 0.1 225 0.69 0.15 29 0.53 0.14 <0.001* ALM index (kg/m2)b 110 7.28 1.08 168 7.28 1.08 17 7.08 1.10 0.745 Femoral neck BMD (g/cm2)c 115 0.892 0.127 172 0.892 0.148 19 0.853 0.134 0.500 Total N N % Total N N % Total N N % P-valuea Female sex 139 62 44.6 233 125 53.6 33 19 57.6 0.174 Unintentional weight loss 139 0 0 232 8 3.4 33 8 24.2 <0.001* Self-reported exhaustion 139 0 0 233 23 9.9 33 25 75.8 <0.001* Low grip strength (<27 kg men; <16 kg women) 139 0 0 233 27 11.6 33 20 60.6 <0.001* Low walking speed (≤0.8 m/s) 139 0 0 225 189 84.0 29 28 96.6 <0.001* Low physical activityd 139 0 0 223 52 23.3 32 28 87.5 <0.001* Emaciated (BMI < 18.5 kg/m2) 139 2 1.4 230 0 0 33 0 0 0.277 Current smoker 139 2 1.4 233 12 5.2 33 1 3.0 0.169 Osteoporosise 118 24 20.3 173 36 20.8 17 6 35.3 0.375 Sarcopenia 126 5 4.0 179 16 8.9 18 5 27.8 0.005* Having 3 or more comorbidities 139 19 13.7 233 48 20.6 33 16 48.5 <0.001* BMI, body mass index; IQR, interquartile range; N, number of participants; SD, standard deviation. a P-value for the difference between the frailty categories. b ALM = appendicular lean mass. c Minimum of left and right femoral neck bone mineral density. d Low physical activity = lowest 20% of activity time as measured by LAPAQ. e Osteoporosis = femoral neck t-score < −2.5 or taking hormone replacement therapy, bisphosphonates, or raloxifene. * P-value < 0.05.

In our sample, the prevalence of frailty and pre-frailty at baseline was 8.1% (men 7.0%, women 9.2%) and 57.5% (men 54.3%, women 60.7%), respectively. Figure 1 illustrates the prevalence of frailty in the 70–74, 75–79, and ≥80 year age groups. These were 5.8%, 9.8%, and 14.3%, respectively, and that of pre-frailty was 55.3%, 59.3%, and 61.9%, respectively. Figure 1B and 1C also shows the age-stratified and gender-stratified prevalence of frailty and pre-frailty. There were no significant differences in frailty status between men and women nor between the age groups in both sexes.

Pooled prevalence of frailty and pre-frailty at baseline (A) and age-stratified and gender-stratified prevalence of frailty and pre-frailty at baseline (B and C).

We next considered interrelationships between SP, OP, or both with frailty. Coexistence of SP, OP, and frailty was observed in 1% of this population. Two per cent of the study sample had SP and OP. Seventy-three per cent had no evidence of SP, OP, or frailty (Figure 2). Among the participants with frailty, 27.8% had a concomitant diagnosis of SP, compared wi