Mortality, bone density and grip strength: lessons from the past and hope for the future?

Objectives: Therapeutic advances in the management of osteoporosis and sarcopenia have occurred at different rates over the last 2 decades. Here we examine associations between grip strength and BMD with subsequent all-cause and cause-specific mortality in a UK community-dwelling cohort. Methods: Data from 495 men and 414 women from the Hertfordshire Cohort Study were analysed. Grip strength was assessed by grip dynamometry, femoral neck BMD was ascertained using DXA and deaths were recorded from baseline (1998-2004) until 31 December 2018. Grip strength and BMD in relation to mortality outcomes (all-cause, cardiovascular-related, cancer-related and mortality due to other causes) were examined using Cox regression with adjustment for age and sex. Results: The mean baseline age of participants was 64.3 years (s.d. 2.5) and 65.9 years (s.d. 2.6) in men and women, respectively. Lower grip strength was associated with increased risk of all-cause mortality [hazard ratio (HR) 1.30 (95% CI 1.06, 1.58), P = 0.010] and cardiovascular-related mortality [HR 1.75 (95% CI 1.20, 2.55), P = 0.004]. In contrast, BMD was not associated with any of the mortality outcomes (P > 0.1 for all associations). Conclusion: We report strong relationships between grip strength and mortality compared with BMD. We hypothesize that this may reflect better recognition and treatment of low BMD in this cohort.

A perspective on muscle phenotyping in musculoskeletal research.

Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.

Do lifestyle, anthropometric and demographic factors associated with muscle strength differ in a UK and Japanese cohort? An exploratory analysis.

BACKGROUND: Muscle weakness is associated with adverse clinical outcomes including disability and mortality. We report demographic, anthropometric and lifestyle correlates of grip strength in UK and Japanese population-based cohorts. AIM: To report prevalence of low grip strength according to 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and 2019 Asian Working Group for Sarcopenia (AWGS 2019) thresholds and to consider correlates of grip strength in Eastern and Western populations. METHODS: UK (1572 men; 1415 women) and Japanese (519 men; 1027 women) participants were recruited from two cohorts harmonised by consensus. Muscle strength was measured by grip strength dynamometry. Potential correlates of grip strength were examined using sex-stratified linear regression; univariate correlates (p < 0.05) were included in mutually adjusted models. RESULTS: Mean (SD) age was 66.2 (2.8) and 65.8 (12.3) in UK and Japanese cohorts, respectively. Prevalence of low grip strength was higher in Japanese participants (EWGSOP2 5.4% versus 2.4%, AWGS 2019 9.0% versus 3.7%). In both cohorts and sexes, univariate correlates of lower grip strength were older age, shorter height, not consuming alcohol, leaving education earlier and greater comorbidity. Apart from older age and shorter height, the only factors related to lower grip strength in mutually adjusted analyses were greater comorbidity among UK participants (kg difference in grip strength (95%CI) per additional comorbidity - 0.60(- 0.98, - 0.21) among men and - 0.50(- 0.86, - 0.13) among women) and not consuming alcohol among Japanese men (- 1.33(- 2.51, - 0.15)). DISCUSSION: Correlates of muscle strength were similar in both cohorts. CONCLUSIONS: A global approach to age-related muscle weakness prevention may be appropriate.

Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study.

We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean ± SD age 77.0 ± 5.1, 73.9 ± 4.9, 80 ± 3.4 years, followed for a mean ± SD 7.8 ± 2.2, 8.1 ± 2.3, 5.3 ± 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

What impact does osteoarthritis have on ability to self-care and receipt of care in older adults? Findings from the Hertfordshire Cohort Study.

Objectives: Living independently remains the aim of older adults, but musculoskeletal conditions and frailty may hamper this. We examined relationships between osteoarthritis with ability to self-care and access to formal/informal care among community-dwelling older adults, comparing results to relationships between other musculoskeletal conditions of ageing (frailty, sarcopenia, osteoporosis) and these outcomes. Design: Data from the Hertfordshire Cohort Study were used. Osteoarthritis (hand, hip or knee) was defined by clinical examination. Osteoporosis was assessed using dual-energy X-ray absorptiometry and medication use. Sarcopenia was assessed using EWSGOP2 criteria, frailty using Fried criteria. Ability to self-care and access to formal/informal care were self-reported. Results: 443 men and women aged approximately 75 years participated. Osteoarthritis was reported by 26.8% participants; 11.8% had low grip strength; 21.4% had osteoporosis; 8.6% had sarcopenia; 7.6% were identified as frail. Most participants (90.7%) reported no problems with self-care, but more than one-fifth (21.4%) reported having received formal or informal care at home in the previous year. Odds of reporting difficulties with self-care were significantly greater (p â€‹< â€‹0.05) for participants with osteoarthritis and for those with frailty, but not for those with osteoporosis or sarcopenia. Odds of receiving care at home in the past year were significantly greater among participants with osteoarthritis and among those with frailty, but not among those with osteoporosis or sarcopenia. Conclusions: Frailty and osteoarthritis were associated with both difficulties with self-care and receipt of care; osteoporosis and sarcopenia were not. These results highlight the contribution of clinical osteoarthritis to ability to live independently in later life, and the need to actively manage the condition in older adults.

Determinants of muscle density and clinical outcomes: Findings from the Hertfordshire Cohort Study.

PURPOSE: The age-related loss of skeletal muscle mass and strength is associated with adverse health outcomes. However, to date, peripheral quantitative computed tomography (pQCT)-derived muscle density has been little studied. We used a well characterised cohort of older adults to identify lifestyle and anthropometric determinants of pQCT-derived muscle density measured 11 years later, and to report relationships between pQCT-derived muscle density with history of falls and prevalent fractures. METHODS: A lifestyle questionnaire was administered to 197 men and 178 women, aged 59-70 at baseline. After a median of 11.5 (IQR 10.9, 12.3) years, pQCT (Stratec XCT2000) of the radius and tibia was performed to measure forearm muscle density (FMD) and calf muscle density (CMD). Presence of falls and fractures since the age of 45 were determined through participant recall; vertebral fractures were also ascertained through vertebral fracture assessment using iDXA. Total hip BMD (TH aBMD) was assessed using DXA. Baseline characteristics in relation to muscle density at follow-up were examined using linear regression; associations between muscle density and prior falls and fractures were investigated using logistic regression. All analyses were adjusted for sex and age. RESULTS: Mean (SD) age at muscle density measurement was 76.3 (2.6) years. Mean (SD) FMD was 79.9 (3.1) and 77.2 (3.2) among males and females, respectively; CMD was 80.7 (2.6) and 78.5 (2.6) among males and females, respectively. Significant sex-differences in muscle density were observed at each site (p < 0.001). Female sex, lower weight, and lower body mass index were associated (p < 0.05) with both lower FMD and CMD. Additional correlates of lower CMD included older age and shorter stature. Lifestyle measures were not associated with muscle density in this cohort. Lower FMD was related to increased risk of previous fracture (odds ratio (95 % CI) per SD lower FMD: 1.42 (1.07, 1.89), p = 0.015) but not after adjustment for TH aBMD (p > 0.08). No significant relationships were seen between muscle density and falls. CONCLUSION: Female sex, older age, and lower BMI were associated with subsequent lower muscle density in older community-dwelling adults. Lower FMD was related to increased risk of previous fracture. Changes in muscle density over time might precede adverse outcomes such as falls and fractures and may be a long-term predictor of frailty. It could be also suggested that muscle density could be a more clinically meaningful surrogate of functional decline and disability than muscle size or mass, but more studies are needed to support this notion.

Functional capacity, sarcopenia, and bone health.

Bone and muscle are recognised as interacting tissues, the so-called 'muscle-bone unit', in which these two tissues communicate to coordinate their development (chemically and metabolically), as well as their response to loading or injury. Musculoskeletal disorders of ageing, specifically osteoporosis and sarcopenia, are highly prevalent in older individuals. They signify a significant burden for older people affecting their mobility, confidence, and quality of life, as well as being a major cost to healthcare systems worldwide. This review considers the coexistence of osteoporosis and sarcopenia in individuals and describes risk factors, clinical consequences, approaches to management, and the link with functional capacity.

Medical history, medication use and physical activity in adults in their eighth and ninth decade of life in the Hertfordshire Cohort Study.

While there are many known health benefits to maintained physical activity levels in late adulthood, there have been very few studies that have considered relationships between morbidity profile and physical activity in the eighth decade of life. We studied 1097 participants, 555 men and 542 women from the Hertfordshire Cohort Study, a UK community based sample. Validated questionnaire based data were used to relate self-reported physical activity (PA) levels to medical history, and medication use. Regression analyses were adjusted for age, BMI, smoker status, alcohol consumption. The mean (SD) age of participants in the study was 80.2 (2.7) years for men and 80.2 (2.6) for women. A higher proportion of men (33.7 %) than women (24 %) were in the high activity score group. 20.8 % of female participants and 22.6 % male participants reported having no comorbid disease; 10.5 % men and 8.4 % women were taking no medication. Higher number of chronic conditions was associated with lower levels of PA [men (OR 0.73, 95 % CI 0.63-0.84, p<0.001); women (OR 0.74, 95 % CI 0.64-0.86, p<0.001)] as was being prescribed a higher number of medications [men (OR 0.88, 95 % CI 0.84-0.93, p<0.001); women (OR 0.86, 95 % CI 0.82-0.91, p<0.001)]. All these associations remained robust following adjustments. Strong relationships were seen in both sexes between PA and taking medication for disorders of the central nervous system and gastrointestinal system, with relationships generally stronger in men. We have observed relationships between comorbid medical history and medication use with physical activity in a cohort of community dwelling older adults. These highlight the need to consider medical history when considering how best to optimize PA in older adults.

Relationships Between Muscle Parameters and History of Falls and Fractures in the Hertfordshire Cohort Study: Do All Muscle Components Relate Equally to Clinical Outcomes?

In previous work, relationships between muscle and bone size and strength have been demonstrated and were stronger in females, suggesting possible sexual dimorphism. Here we examine sex-specific associations between individual muscle sarcopenia components with clinical outcomes (falls and fractures). 641 participants were recruited. Muscle mass was assessed as cross-sectional area (CSA) by peripheral quantitative computed tomography of the calf, grip strength (GpS) by Jamar dynamometry and function by gait speed (GtS). Falls and fractures were self-reported. Ordinal and logistic regression were used to examine the associations between muscle measurements and outcomes with and without adjustment for confounders. Mean (SD) age was 69.3 (2.6) years. CSA, GpS, and GtS were greater among males (p < 0.002). A higher proportion of females had fallen since age 45 (61.3% vs 40.2%, p < 0.001); in the last year (19.9% vs 14.1%, p = 0.053); and reported a previous fracture since age 45 (21.8% vs 18.5%, p = 0.302), than males. Among females, greater CSA was related to reduced risk of falling and fewer falls in the previous year in fully adjusted analysis only (p < 0.05); higher GpS was related to lower risk of falls since age 45 in unadjusted analysis (p = 0.045) and lower risk of fracture since age 45 in both unadjusted and fully adjusted analysis (p < 0.045). No statistically significant associations were observed for GtS among either sex for any relationships between muscle measurements and clinical outcomes studied. We observed relationships between muscle mass and strength but not function with falls and fractures in females only; further longitudinal studies are required to reproduce these results.

Physical Activity and Diet in a Global Pandemic: An Investigation of the Impact of COVID-19 on Factors Relevant for Musculoskeletal Health at Two Different Stages of the Lifecourse.

Background: Physical activity, nutrition and other lifestyle factors play important roles in maintaining musculoskeletal health. The coronavirus disease (COVID-19) originated in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020, and led to widespread behaviour change. The aim of this study was to use two existing cohorts, the Hertfordshire Cohort Study (HCS) and Health and Employment After Fifty Study (HEAF), to understand how wave one of the COVID-19 pandemic impacted lifestyle factors associated with musculoskeletal health in the UK. Methods: 125 eligible participants, 65 males and 60 females (drawn from the HCS study, median (IQR) age 84.3 (82.4-86.6) years, all Caucasian, and community dwelling) were contacted by telephone and asked to complete a questionnaire administered by a trained researcher. Data collection occurred over the period July 2020 to February 2021. 2469 participants, 1086 men and 1383 women (drawn from the HEAF study, median age 65.7 (62.0-69.3) years, mostly Caucasian and community dwelling) completed an online questionnaire in March 2021. Results: In HCS, 47% respondents reported being less physically active than before the pandemic (and only 5% more so), 27% said they consumed less alcohol compared to pre-pandemic times (and only 3% more so), and 18% reported eating less than before, although quality of diet was generally unchanged over this timeframe surveyed. In HEAF, 44% participants said they were less active than before the pandemic, while 17% reported being more active. The majority of participants reported no changes in alcohol consumption and diet; however, 19% said they drank more than before (32% of which was above recommended levels), 16% said their diet was less healthy, and 19% reported eating more than before. Conclusion: We have reported the experience of the first wave of the COVID-19 pandemic among participants of two Caucasian community dwelling UK cohorts, highlighting the impact of the pandemic on lifestyle factors associated with musculoskeletal health. Changed physical activity levels were reported in a high proportion of respondents in both studies; an investigation of reversibility of these changes is required.

Associations of osteoporosis and sarcopenia with frailty and multimorbidity among participants of the Hertfordshire Cohort Study.

BACKGROUND: Ageing is commonly associated with sarcopenia (SP) and osteoporosis (OP), both of which are associated with disability, impaired quality of life, and mortality. The aims of this study were to explore the relationships between SP, OP, frailty, and multimorbidity in community-dwelling older adults participating in the Hertfordshire Cohort Study (HCS) and to determine whether coexistence of OP and SP was associated with a significantly heavier health burden. METHODS: At baseline, 405 participants self-reported their comorbidities. Cut-offs for low grip strength and appendicular lean mass index were used according to the EWSGOP2 criteria to define SP. OP was diagnosed when T-scores of < -2.5 were present at the femoral neck or the participant reported use of the anti-OP medications including hormone replacement therapy (HRT), raloxifene, or bisphosphonates. Frailty was defined using the standard Fried definition. RESULTS: One hundred ninety-nine men and 206 women were included in the study. Baseline median (interquartile range) age of participants was 75.5 (73.4-77.9) years. Twenty-six (8%) and 66 (21.4%) of the participants had SP and OP, respectively. Eighty-three (20.5%) reported three or more comorbidities. The prevalence of pre-frailty and frailty in the study sample was 57.5% and 8.1%, respectively. Having SP only was strongly associated with frailty [odds ratio (OR) 8.28, 95% confidence interval (CI) 1.27, 54.03; P = 0.027] while the association between having OP alone and frailty was weaker (OR 2.57, 95% CI 0.61, 10.78; P = 0.196). The likelihood of being frail was substantially higher in the presence of coexisting SP and OP (OR 26.15, 95% CI 3.13, 218.76; P = 0.003). SP alone and OP alone were both associated with having three or more comorbidities (OR 4.71, 95% CI 1.50, 14.76; P = 0.008 and OR 2.86, 95% CI 1.32, 6.22; P = 0.008, respectively) although the coexistence of SP and OP was not significantly associated with multimorbidity (OR 3.45, 95% CI 0.59, 20.26; P = 0.171). CONCLUSIONS: Individuals living with frailty were often osteosarcopenic. Multimorbidity was common in individuals with either SP or OP. Early identification of SP and OP not only allows implementation of treatment strategies but also presents an opportunity to mitigate frailty risk.

A study of diet in older community-dwelling adults in the UK during the COVID-19 pandemic: Findings from the Southampton Longitudinal Study of Ageing (SaLSA).

Introduction: Adequate nutrition is important for health in later life. Older adults are especially vulnerable to adverse outcomes following infection by COVID-19 and have commonly spent a disproportionate time within their own homes to reduce risk of infection. There are concerns that advice to shield may have led to malnutrition as older adults may modify daily routines including usual shopping habits. The aims of this study were to report self-reported pandemic-related changes in diet and examine lifestyle and medical correlates of these changes in older UK community-dwelling adults. Methods: We recruited 491 participants from the city of Southampton, UK. Participants completed a postal questionnaire in summer/autumn 2021, over a year after the first UK national lockdown was announced. The questionnaire ascertained demographic and lifestyle factors, in addition to number of comorbidities, nutrition risk scores, and presence of frailty. Associations between these participant characteristics in relation to self-reported changes in diet quality (lower, similar or higher when compared to before the first lockdown) were examined using ordinal logistic regression. Results: Median (lower quartile, upper quartile) age was 79.8 (77.0, 83.7) years. Overall, 11 (4.9%) men and 25 (9.4%) women had poorer diet quality compared to before the first UK lockdown. The following participant characteristics were associated with increased risk of being in a worse category for change in diet quality after adjustment for sex: lower educational attainment (p = 0.009); higher BMI (p < 0.001); higher DETERMINE (a malnutrition assessment) score (p = 0.004); higher SARC-F score (p = 0.013); and self-reported exhaustion in the previous week on at least 3 days (p = 0.002). Conclusions: Individuals at higher nutritional risk were identified as reporting increased risk of deterioration in diet quality during the pandemic. Further investigation of the factors leading to these changes, and an understanding of whether they are reversible will be important, especially for future pandemic management.

Determinants of circulating 25-hydroxyvitamin D concentration and its association with musculoskeletal health in midlife: Findings from the Hertfordshire Cohort Study.

INTRODUCTION: Several studies have reported the importance of vitamin D status to musculoskeletal health in populations of older adults. Here we report relationships between circulating serum 25(OH)D and musculoskeletal health in a community cohort of UK adults in midlife and investigate whether environmental (dietary intake, use of supplements) and/or genetic factors (4 SNPs previously related to vitamin D status) play more significant roles in determining vitamin D status in this population. METHODS: Participants were recruited from the Hertfordshire Cohort Study, an established longitudinal cohort study of community dwelling adults and were seen at baseline and follow up 9-12 years later. Lumbar spine and total femur BMD were measured at baseline using a Hologic QDR 4500 instrument. Osteoarthritis (OA) was defined by radiographs of the knees graded according to Kellgren & Lawrence at both time points. Serum 25(OH)D concentrations were measured using a DiaSorin Liaison chemiluminescent assay. Genotyping of 4 SNPs previously associated with 25(OH)D values were assessed: (rs12785878 (DHCR7), rs10741657 (CYP2R1) and rs6013897 (CYP24A1)) and a fourth SNP (rs4588), described as "a near-perfect proxy (i.e. substitute) for rs2282679 on the GC gene". RESULTS: 820 subjects (397 men, 423 women) participated at baseline, and 339 of these 820 subjects (164 men; 175 women) participated in a follow up study of OA progression. The median (IQR) age of participants at baseline was 64.0 (61.8-66.5) and 65.5 (63.3-67.6) for men and women respectively. Median circulating levels of 25(OH)D were 44.6 (35.0-63.0) nmol/L and 41.3 (29.8-53.5) nmol/L in men and women respectively. Circulating 25(OH)D was strongly associated with season of blood testing (p < 0.001). The greatest variance in a model of vitamin D status that included the four SNPs measured, season, and whether participants reported taking vitamin D supplements was explained by season of assay (17.9% men; 15.8% women). Higher femoral neck BMD was observed in men with higher baseline vitamin D status, after adjustment for age, season, BMI, smoker status, alcohol consumption, physical activity and social class (p = 0.01). Associations between 25(OH)D and BMD in women were not statistically significant in this population. There were no associations between circulating 25(OH)D and radiographic knee OA at either time point after adjustment for confounders and for duration of follow-up. CONCLUSION: Circulating 25(OH)D levels were generally lower than is recommended in community dwelling adults in midlife, with marked seasonal variation observed, but relationships with reported vitamin D supplementation were weaker. Circulating 25(OH)D was directly associated with hip BMD in men but relationships with BMD in women and radiographic OA were not seen in this sample.

Self-reported Sleep Quality and Bone Outcomes in Older Adults: Findings from the Hertfordshire Cohort Study.

Sleep duration may be associated with risk of osteoporosis, with suggestions that too little or indeed too much sleep may be detrimental to bone health. In this study, we considered whether perceived sleep quality is also associated with bone health in older adults. We explored this association in a cohort of 443 older community-dwelling UK adults. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); poor sleep quality was defined as > 5 on this score system. Bone density, shape and microarchitecture were assessed using dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HRpQCT). Thirty-seven percent of men and 43% of women had a PSQI score greater than 5, indicative of poor perceived sleep. We found that quality of sleep was associated with altered bone microarchitecture. In men, poor sleep quality was associated with lower radial trabecular (4% slice, p < 0.04) and cortical (66% slice, p = 0.02) bone mineral density, as well as decreased tibial cortical density (p < 0.02) and increased porosity (p < 0.04), but increased size of the tibia (p < 0.04). In women, poor perceived sleep quality was associated with thinner (p < 0.03) and less dense (p < 0.04) cortices of the radius, but greater tibial trabecular number (p < 0.02) and lower separation (p < 0.04). Relationships with DXA parameters were non-significant after adjustment for confounders. Taking sleep medications was associated with decreased tibial size (38% and 66% slices) and strength in women (all p < 0.05), but not in men. Perceived sleep quality was associated with altered bone density and microarchitecture in older adults, and these differences varied according to biological sex and site. Further work is indicated to investigate possible mechanisms underlying these observations.

Interaction of Nutrition and Exercise on Bone and Muscle.

Physical activity and nutritional factors, such as calcium and vitamin D intake, have been shown in numerous studies to be beneficial to musculoskeletal health at different points in the lifecourse. However, the evidence that physical activity and nutrition may act synergistically for benefit is far more sparce; the best data come from studies that consider calcium, vitamin D or creatine supplementation in combination with physical activity interventions to promote better musculoskeletal health. Some observational data also suggest that a 'healthier' lifestyle, characterised by a more 'prudent' diet and higher reported levels of physical activity is also associated with better musculoskeletal health in late adulthood. Given the public health burden of osteoporosis and sarcopenia in our aging population, well designed randomised controlled trials are now timely and much needed.

A probability score to aid the diagnosis of suspected giant cell arteritis.

OBJECTIVES: We propose a GCA probability score intended to help to risk-stratify patients referred by general practitioners with suspected GCA into those with high probability of GCA versus low probability of GCA. In this pilot study we evaluated the diagnostic accuracy of this proposed scoring system. METHODS: A scoring system was proposed based on clinical experience. Retrospective analysis was conducted from clinical notes of consecutive patients presenting to a Fast Track Pathway clinic between August 2016 and August 2017. The GCA Probability Score was calculated for each patient and receiver operating characteristic (ROC) curve plotted. RESULTS: Of 122 consecutive patients, full data were available for calculation of GCA probability score in all patients except one (excluded from this analysis). The area under the ROC curve was 0.953 (95% confidence interval: 0.911, 0.994). The ROC curve showed an optimal cut point of 9.5 out of a possible score of 32. At this cut-point there was a sensitivity of 95.7% and specificity 86.7%, and 88.4% of cases were correctly classified. CONCLUSIONS: The GCA Probability Score is a promising and feasible tool for risk stratification of patients referred by general practitioners with suspected GCA. In a fast track clinic setting this aids exclusion of GCA in low probability cases and confirmation of disease in high probability disease. Refinement and subsequent external validation of this score is required.

Tocilizumab (Actemra).

Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA). This article provides an overview of TCZ including looking into the past at the discovery of interleukin-6 (IL-6) as a pro-inflammatory cytokine. It also looks at how tocilizumab was developed, manufactured and tested to ensure both safety and efficacy in a human population. The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).

Thrombopoetin receptor agonist therapy in thrombocytopenia: ITP and beyond.

Eltrombopag is well established in treatment of severe immune thrombocytopenia (ITP) and is increasingly commonplace in second-line management. A role is also suggested for both bridging therapy for surgery, as well as treating thrombocytopenia due to non-immune aetiologies. We present the largest single-centre experience with eltrombopag, with our cohort of 62 patients. Patients with severe ITP (n = 34) had 91·2% response, which was sustained over a median of 18·5 months. In 41·4% of ITP cases (n = 14), complete response (CR- platelet count >100 × 109 /l) was achieved and in 2 cases, therapy was stopped and CR maintained. In our bridging group (n = 15) with a higher baseline platelet count, 93·3% achieved a CR. In the non-ITP group (n = 13), a response was achieved in 76·9%. In all groups, side effects were transient, with the drug discontinued in 2 patients due to minor complications (rash, nausea, diarrhoea). We conclude that eltrombopag is both effective and well tolerated as therapy in severe ITP. It is also advantageous in ITP patients who do not normally require therapy, but need a temporary platelet count boost pre-procedure. Furthermore, there are potentially far wider implications for the use of eltrombopag in counteracting thrombocytopenia beyond ITP, which merit further investigation.

Quality improvement: audio-visual tools are a valuable supplement when obtaining consent for lumbar punctures.

Neurological conditions present a challenge when obtaining consent for lumbar punctures (LPs), as patients often have -visual, hearing or cognitive impairments. The aim of this -project was to improve the quality of the consent process for LPs. Surveys of doctors and patients suggested there was scope to standardise and improve information provided during the consent process. A patient information video was -developed using online software and shown to patients using tablet -computers. Patient surveys were distributed to re-assess the quality of the process for obtaining consent. There was a -significant improvement (p=0.031) in the median response score after the video was presented to the same group of patients. The use of patient information videos -significantly improves understanding and recall of the procedure, and -satisfaction with the consent process. In conclusion, audio--visual tools are a valuable tool for standardising and -improving the process of gaining consent for LPs.