Multimorbidity and risk of falls, fractures, and joint replacements over two decades: Findings from the Hertfordshire Cohort Study.

AIM: To examine the relationship between level of morbidity burden and long-term risk of fractures, falls, and joint replacements in the community-dwelling participants of the Hertfordshire Cohort Study. METHODS: Data were analyzed from 2997 individuals (age 59-73 at baseline). Outcomes (fractures, falls, and lower limb joint replacements) were identified using ICD-10 and OPCS-4 codes from Hospital Episode Statistics data, available from baseline (1998-2004) until December 2018. Number of systems medicated (marker of morbidity level) in relation to risk of outcomes was examined using sex-stratified Cox regression. RESULTS: Among both men and women, a greater number of systems medicated was related to increased risk of falls (P < 0.001) and lower limb joint replacements (P < 0.003). More systems medicated was only related to increased risk of fracture among women (P-values for trend of <0.001 among women and 0.186 among men). CONCLUSIONS: Higher morbidity was associated with increased risk of adverse health outcomes related to poor musculoskeletal health, but these relationships varied according to the musculoskeletal outcome studied. Intervention strategies to reduce multimorbidity among middle-aged and older people may hence reduce the burden of musculoskeletal aging. Geriatr Gerontol Int 2024; ••: ••-••.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Acquisition of peak bone mass in a Norwegian youth cohort: longitudinal findings from the Fit Futures study 2010-2022.

In a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass. PURPOSE: To examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood. METHOD: In a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16-19 years into adulthood (age of 26-29) on three occasions: 2010-2011 (Fit Futures 1 (FF1)), 2012-2013 (FF2), and 2021-2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3. RESULTS: From the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059-1.082) to 1.076 (1.065-1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029-1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091-1.116); 27 years, 1.063 (1.050-1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133-1.148); 27 years, 1.204 (1.196-1.212), p < 0.001; males: 16 years, 1.179 (1.170-1.188); 27 years, 1.310 (1.296-1.315), p < 0.001). CONCLUSION: BMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.

Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

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.

Could self-reported physical performance help predict individuals at the highest risk of mortality and hospital admission events in clinical practice? Findings from the Hertfordshire Cohort Study.

AIM: To consider how self-reported physical function measures relate to adverse clinical outcomes measured over 20 years of follow-up in a community-dwelling cohort (aged 59-73 at baseline) as compared with hand grip strength, a well-validated predictor of adverse events. BACKGROUND: Recent evidence has emphasized the significant association of physical activity, physical performance, and muscle strength with hospital admissions in older people. However, physical performance tests require staff availability, training, specialized equipment, and space to perform them, often not feasible or realistic in the context of a busy clinical setting. METHODS: In total, 2997 men and women were analyzed. Baseline predictors were measured grip strength (Jamar dynamometer) and the following self-reported measures: physical activity (Dallosso questionnaire); physical function score (SF-36 Health Survey); and walking speed. Participants were followed up from baseline (1998-2004) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Predictors in relation to the risk of mortality and hospital admission events were examined using Cox regression with and without adjustment for sociodemographic and lifestyle characteristics. FINDINGS: The mean age at baseline was 65.7 and 66.6 years among men and women, respectively. Over follow-up, 36% of men and 26% of women died, while 93% of men and 92% of women were admitted to hospital at least once. Physical activity, grip strength, SF-36 physical function, and walking speed were all strongly associated with adverse health outcomes in both sex- and fully adjusted analyses; poorer values for each of the predictors were related to greater risk of mortality (all-cause, cardiovascular-related) and any, neurological, cardiovascular, respiratory, any fracture, and falls admissions. SF-36 physical function and grip strength were similarly associated with the adverse health outcomes considered.

Lifecourse correlates of self-rated health and associations with subsequent mortality: findings from the Hertfordshire Cohort Study.

Background: Poor self-rated health (SRH) has been shown to predict adverse health outcomes among older people, however these associations have traditionally only been considered at one point in the lifecourse, usually midlife or later. Here we examined lifecourse correlates of SRH in early, mid and later life, relating these to subsequent risk of mortality in a community-dwelling cohort. Methods: 2989 men and women from the Hertfordshire Cohort Study (HCS) were included in this study. The HCS was initially retrospective and linked contemporary health outcome data to early life data available from health ledgers but investigations from baseline (1998-2004, aged 59-73) onwards have been prospective. At baseline, participants completed an initial clinic visit, which included questionnaire assessment of SRH, reported as 'excellent', 'very good', 'good', 'fair', or 'poor'. Socioeconomic, lifestyle, mental health and demographic information was also collected. Deaths were recorded from baseline to 31/12/2018. Baseline characteristics in relation to SRH were examined using sex-stratified ordinal logistic regression; these factors were examined in relation to mortality using sex-stratified Cox regression. Statistically significant exposures were then included in sex-stratified mutually-adjusted models. Results: In mutually-adjusted analysis, numerous contemporaneous correlates of poorer SRH in the seventh decade were identified and included obesity, lower physical activity, greater comorbidity and higher levels of depression among men and women. For example, odds ratios for being in a lower category of SRH were as follows: obese (BMI≥30) vs underweight/healthy (BMI<25) (men 1.60 (1.21, 2.11), women 1.65 (1.25, 2.17)) and per additional system medicated (men 1.62 (1.47, 1.77), women 1.53 (1.41, 1.66)). By contrast, factors earlier in the lifecourse (early growth, age left full-time education) were not associated with SRH in late adulthood. 36% of men and 26% of women died during follow-up. Hazard ratios (95% CI) for mortality per lower category of SRH were 1.22 (1.10,1.36) among men and 1.17 (1.01,1.35) among women after adjustment for age, BMI, smoking, physical activity, diet quality, education, home ownership status, comorbidity level and depression levels, suggesting residual confounding by other unrecorded factors that are related to SRH. Conclusions: Poorer SRH in the seventh decade was a risk factor for mortality. Importantly modifiable adverse health behaviours in the seventh decade, such as low physical activity, were associated with poorer SRH and later mortality after adjustment for socioeconomic factors and comorbidity level. By contrast early growth and education were not related to later SRH. These data suggest that attention to lifestyle in late midlife may be associated with better SRH and subsequent health outcomes, highlighting the value of intervention at this stage of the lifecourse.

Fracture Risk and Health Profiles Differ According to Relationship Status: Findings from the Hertfordshire Cohort Study.

Registry studies have suggested associations between relationship status and fracture risk. We considered associations between relationship status and incident fracture in the Hertfordshire Cohort Study, comprising community-dwelling older adults, and explored associations between socioeconomic and lifestyle factors with relationship status. 2997 participants completed a baseline questionnaire (1998-2004) and clinic visit. Participants were followed up until December 2018 using Hospital Episode Statistics, which report clinical outcomes using codes from the 10th revision of the International Classification of Diseases (ICD-10); these codes were used to ascertain incident fractures. Relationship status (not currently married/cohabiting vs currently married/cohabiting) at baseline was examined in relation to incident fracture using Cox regression. Associations between baseline characteristics and relationship status were examined using logistic regression. Mean baseline age was 66.2 years. 80% were married/cohabiting at baseline; 15% had an incident fracture (mean (SD) follow-up duration: 14.4 (4.5) years). The following were related to greater likelihood of not being married/cohabiting: older age (women only); higher BMI (women only); current smoking; high alcohol consumption (men only); poorer diet quality (men only); lower physical activity; leaving school before age 15 (women only); and not owning one's home. Those not married/cohabiting had greater risk of incident fracture compared to those who were (age-adjusted hazard ratios (95% CI) 1.58 (1.06, 2.38) among men, 1.35 (1.06, 1.72) among women); associations were attenuated after accounting for the above factors associated with relationship status in the corresponding sex. This suggests that differences in health profiles and lifestyle according to relationship status may explain the association between relationship status and fracture risk.

General self-efficacy, not musculoskeletal health, was associated with social isolation and loneliness in older adults during the COVID-19 pandemic: findings from the Hertfordshire Cohort Study.

BACKGROUND: Social isolation and loneliness are prevalent among older adults. This study investigated factors influencing worsening social isolation and loneliness in community-dwelling older adults during the COVID-19 pandemic, focusing on musculoskeletal conditions, falls, and fractures. METHODS: We studied 153 participants from the Hertfordshire Cohort Study. Baseline assessments (2019-20) included osteoporosis, clinical osteoarthritis, fractures after age 45 years, falls in previous year, and lifestyle factors. Self-efficacy was assessed using a shortened General Self-Efficacy Scale. Social isolation was assessed using the 6-item Lubben Social Network Scale. Follow-up (2020-21) assessments included social isolation and loneliness using the 6-item De Jong-Gierveld scale for emotional, social, and overall loneliness. RESULTS: Baseline median age was 83.1 years. A history of smoking predicted worsening social isolation (p = 0.046). Being married (p = 0.026) and higher self-efficacy scores (p = 0.03) predicted reduced social isolation at follow-up. Greater alcohol consumption was associated with higher overall loneliness (p = 0.026). Being married was related to a 36% (95% CI: 3%, 58%) reduction in emotional loneliness (p = 0.037). No musculoskeletal condition was associated with social isolation or loneliness. However, we observed a 22% (14%, 30%; p < 0.001) reduction in emotional loneliness and a 12% (4%, 20%; p = 0.003) reduction in overall loneliness per unit increase in self-efficacy score. CONCLUSIONS: No musculoskeletal condition was associated with increased social isolation or loneliness, but longitudinal studies in larger samples are required. Greater self-efficacy was associated with reduced social isolation and reduced loneliness. Interventions promoting self-efficacy in older adults may reduce isolation and loneliness in this age group.

Musculoskeletal health and life-space mobility in older adults: Findings from the Hertfordshire Cohort Study.

This study explores the relationship between musculoskeletal conditions of ageing and life-space mobility (LSM) in 1110 community-dwelling older adults from the Hertfordshire Cohort Study. LSM is a novel measure which captures ability to mobilise within the home, locally and more widely. Among men, older age, care receipt, not driving a car, lower wellbeing, and reduced physical function were associated with lower LSM, while in women only driving status and physical function were associated with LSM. Osteoporosis, arthritis, and fractures had no significant associations with LSM in either gender. These findings provide support for sex-specificity in the determinants of LSM and inform novel approaches to improving mobility and health in older age.

The serum small non-coding RNA (SncRNA) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults.

Small noncoding RNAs (sncRNAs) are implicated in age-associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider circulating sncRNA transcriptome of older individuals and associations with sarcopenia and IR. sncRNA expression including miRNAs, transfer RNAs (tRNAs), tRNA-associated fragments (tRFs), and piwi-interacting RNAs (piRNAs) was measured in serum from 21 healthy and 21 sarcopenic Hertfordshire Sarcopenia Study extension women matched for age (mean 78.9 years) and HOMA2-IR. Associations with age, sarcopenia and HOMA2-IR were examined and predicted gene targets and biological pathways characterized. Of the total sncRNA among healthy controls, piRNAs were most abundant (85.3%), followed by tRNAs (4.1%), miRNAs (2.7%), and tRFs (0.5%). Age was associated (FDR < 0.05) with 2 miRNAs, 58 tRNAs, and 14 tRFs, with chromatin organization, WNT signaling, and response to stress enriched among gene targets. Sarcopenia was nominally associated (p < .05) with 12 tRNAs, 3 tRFs, and 6 piRNAs, with target genes linked to cell proliferation and differentiation such as Notch Receptor 1 (NOTCH1), DISC1 scaffold protein (DISC1), and GLI family zinc finger-2 (GLI2). HOMA2-IR was nominally associated (p<0.05) with 6 miRNAs, 9 tRNAs, 1 tRF, and 19 piRNAs, linked with lysine degradation, circadian rhythm, and fatty acid biosynthesis pathways. These findings identify changes in circulating sncRNA expression in human serum associated with chronological age, sarcopenia, and IR. These may have clinical utility as circulating biomarkers of ageing and age-associated pathologies and provide novel targets for therapeutic intervention.

The impact of methods for estimating bone health and the global burden of bone disease: [review] / Impacto de los métodos para medir la salud ósea y la carga global de enfermedades óseas: [revisión]

Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.

La osteoporosis constituye un importante problema de salud pública debido a su asociación con fracturas relacionadas con la edad. Las tasas de fractura generalmente son más altas en mujeres caucásicas que en otros grupos poblacionales. Los principales determinantes incluyen deficiencia de estrógeno en mujeres, bajo índice de masa corporal, consumo de tabaco y alcohol, escaso consumo de calcio, inactividad física y algunas drogas y enfermedades. De este modo, la modificación de la actividad física y el consumo de nutrimentos con calcio y vitamina D deben complementar los tratamientos en alto riesgo. Además, el recientemente desarrollado algoritmo de la OMS para la evaluación de riesgo de fractura absoluto a 10 años constituye una herramienta que permite plantear eficientemente diversas terapias a aquellos que están en riesgo. Los factores de riesgo, junto con la densidad mineral ósea y los índices bioquímicos de regeneración ósea pueden utilizarse para obtener riesgos de fractura absolutos así como umbrales costo-utilidad que justifiquen el tratamiento. Estos datos proveerán una base para su traducción en estrategias de salud pública con la finalidad de prevenir la osteoporosis tanto en los individuos como en la población en general.