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.

Relationships between non-communicable disease, social isolation and frailty in community dwelling adults in later life: findings from the Hertfordshire Cohort Study.

BACKGROUND: Social relationships play a fundamental role in individuals' lives and health, and social isolation is prevalent among older people. Chronic non-communicable diseases (NCDs) and frailty are also common in older adults. AIMS: To examine the association between number of NCDs and social isolation in a cohort of community-dwelling older adults in the UK, and to consider whether any potential association is mediated by frailty. METHODS: NCDs were self-reported by 176 older community-dwelling UK adults via questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale. Frailty was assessed by the Fried phenotype of physical frailty. RESULTS: The median (IQR) age of participants in this study was 83.1 (81.5-85.5) years for men and 83.8 (81.5-85.9) years for women. The proportion of socially isolated individuals was 19% in men and 20% in women. More women (18%) than men (13%) were identified as frail. The number of NCDs was associated with higher odds of being isolated in women (unadjusted odds ratio per additional NCD: 1.65, 95% CI 1.08, 2.52, p = 0.021), but not in men, and the association remained robust to adjustment, even when accounting for frailty (OR 1.85, 95% CI 1.06, 3.22, p = 0.031). DISCUSSION: Number of self-reported NCDs was associated with higher odds of social isolation in women but not in men, and the association remained after considering frailty status. CONCLUSIONS: Our observations may be considered by healthcare professionals caring for community-dwelling older adults with multiple NCDs, where enquiring about social isolation as part of a comprehensive assessment may be important.

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.

The relationship of nutritional risk with diet quality and health outcomes in community-dwelling older adults.

OBJECTIVES: To identify early nutritional risk in older populations, simple screening approaches are needed. This study aimed to compare nutrition risk scores, calculated from a short checklist, with diet quality and health outcomes, both at baseline and prospectively over a 2.5-year follow-up period; the association between baseline scores and risk of mortality over the follow-up period was assessed. METHODS: The study included 86 community-dwelling older adults in Southampton, UK, recruited from outpatient clinics. At both assessments, hand grip strength was measured using a Jamar dynamometer. Diet was assessed using a short validated food frequency questionnaire; derived 'prudent' diet scores described diet quality. Body mass index (BMI) was calculated and weight loss was self-reported. Nutrition risk scores were calculated from a checklist adapted from the DETERMINE (range 0-17). RESULTS: The mean age of participants at baseline (n = 86) was 78 (SD 8) years; half (53%) scored 'moderate' or 'high' nutritional risk, using the checklist adapted from DETERMINE. In cross-sectional analyses, after adjusting for age, sex and education, higher nutrition risk scores were associated with lower grip strength [difference in grip strength: - 0.09, 95% CI (- 0.17, - 0.02) SD per unit increase in nutrition risk score, p = 0.017] and poorer diet quality [prudent diet score: - 0.12, 95% CI (- 0.21, - 0.02) SD, p = 0.013]. The association with diet quality was robust to further adjustment for number of comorbidities, whereas the association with grip strength was attenuated. Nutrition risk scores were not related to reported weight loss or BMI at baseline. In longitudinal analyses there was an association between baseline nutrition risk score and lower grip strength at follow-up [fully-adjusted model: - 0.12, 95% CI (- 0.23, - 0.02) SD, p = 0.024]. Baseline nutrition risk score was also associated with greater risk of mortality [unadjusted hazard ratio per unit increase in score: 1.29 (1.01, 1.63), p = 0.039]; however, this association was attenuated after adjustment for sex and age. CONCLUSIONS: Cross-sectional associations between higher nutrition risk scores, assessed from a short checklist, and poorer diet quality suggest that this approach may hold promise as a simple way of screening older populations. Further larger prospective studies are needed to explore the predictive ability of this screening approach and its potential to detect nutritional risk in older adults.

The association between social isolation and musculoskeletal health in older community-dwelling adults: findings from the Hertfordshire Cohort Study.

PURPOSE: Social isolation has been associated with both physical and psychological adverse outcomes and is prevalent in older adults. We investigated the impact of social isolation on bone mineral density (BMD) and physical capability in community-dwelling older adults. METHODS: Data were collected in 2011 and 2017 from the Hertfordshire Cohort Study. In 2011, we assessed social isolation using the six-item Lubben Social Network Scale (LSNS-6) and the Maastricht Social Participation Profile (MSSP) and depressive and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Physical capability was assessed by performing tests of gait speed, chair stands, timed up and go and balance at both time points. BMD was assessed using dual X-ray absorptiometry (DXA) at both time points. RESULTS: Data were available from 369 participants in 2011 and 184 in 2017. Forty percent of men and 42.4% of women were socially isolated. Isolated participants had higher odds of depressive disorder (OR 3.01, 95% CI 1.27-7.11, p < 0.02). Social isolation at baseline was associated with poor physical capability scores at follow-up (OR 5.53, 95% CI 1.09-27.99, p < 0.04). No associations were found between social isolation and BMD at either time point. CONCLUSIONS: Social isolation was associated with higher odds of having depressive symptoms and predicted the development of poor physical capability 6 years later. Further longitudinal studies that include loneliness as a covariate are warranted.

Poor sleep quality and physical performance in older adults.

OBJECTIVES: This study aimed to examine the association between sleep quality and physical performance among a group of UK community-dwelling older adults, according to sex. METHODS: Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Physical performance was assessed using a short physical performance battery (SPPB), a timed up-and-go, and a hand-grip strength test. RESULTS: Of 591 eligible study members, 401 completed the Pittsburgh Sleep Quality Index. In regression analyses, men who reported poor sleep quality were significantly more likely to have a poor SPPB score, even after adjustment for confounding factors (OR = 2.54, 95% CI 1.10-5.89, P= .03). The direction of the relationship was reversed among women, where those who reported poor sleep were less likely to have a low SPPB score (OR = 0.36, 95% CI 0.15-0.85, P = .02). Poor sleep quality was associated with poorer hand-grip strength among women (regression coefficient = -0.34 z score, 95% CI -0.64, -0.04, P = .03), but this relationship was not observed among men (regression coefficient = 0.28 z score, 95% CI -0.01, 0.57, P = .06). CONCLUSION: We found evidence of an association between poor sleep quality and poorer physical performance in older adults, though there appear to be important sex differences.

Does self-report of multimorbidity in later life predict impaired physical functioning, and might this be useful in clinical practice?

BACKGROUND: Multimorbidity has been shown in several studies to relate to impaired physical function in later life. AIMS: To examine if self-report of multimorbidity predicts impaired physical functioning, as assessed by formal physical function testing, in community-dwelling older adults. METHODS: Non-communicable diseases (NCDs) were self-reported by 443 older community-dwelling UK adults via questionnaire, asking the question: 'Have you been told by a doctor that you have any of the following conditions?' Assessments of walking speed, chair stands and balance allowed us to create a composite score (0-12) on which impaired physical functioning was defined as ≤ 9. RESULTS: The mean age of participants was 75.5 ± 2.5 years for men and 75.8 ± 2.6 for women. The proportion of individuals with impaired physical functioning was 71.2% in women and 56.9% in men. Having four or more NCDs was associated with an increased risk of poor physical function in men and women (p < 0.05). The number of medications and medicated systems was associated with gait speed (p < 0.03 and < 0.02, respectively) and timed up-and-go tests (p < 0.03 and < 0.02, respectively) in women but not men. DISCUSSION AND CONCLUSION: Self-report of 4 or more NCDs was associated with an increased risk of poor physical function, an outcome which has previously been associated with adverse clinical sequelae. This observation may inform development of a simple screening tool to look for poor physical function in older adults.

Findings from an exploration of a social network intervention to promote diet quality and health behaviours in older adults with COPD: a feasibility study.

BACKGROUND: Diet quality in older people with chronic obstructive pulmonary disease (COPD) is associated with better health and lung function. Social factors, such as social support, social networks and participation in activities, have been linked with diet quality in older age. A social network tool-GENIE (Generating Engagement in Network Involvement)-was implemented in a COPD community care context. The study aimed to assess the feasibility of the GENIE intervention to promote diet quality and other health behaviours in COPD. METHODS: Twenty-two community-dwelling older adults with COPD were recruited from a local COPD service. Participants were offered usual care or the GENIE intervention. Process evaluation methods were used to assess intervention implementation, context and mechanisms of impact; these included observations of patient interactions with the intervention, documented in observational field notes and in films of a patient group discussion. Diet quality was assessed by food frequency questionnaire; 'prudent' diet scores were used to describe diet quality at baseline and at 3-month follow-up. Change in diet quality was expressed per month, from baseline to follow-up. RESULTS: Feasibility data showed that the GENIE intervention could be implemented in this sample of community-living older people. The intervention was acceptable to clinicians and older people with COPD, especially for those with less severe disease, when facilitated appropriately and considering the levels of literacy of participants. There was no significant change in diet quality in the intervention group over the follow-up period (median change in prudent diet score per month (interquartile range (IQR), 0.03 (- 0.24-0.07)), whereas an overall fall in diet quality was observed in the control group (- 0.15 (- 0.24-0.03)). CONCLUSION: The process evaluation findings suggest that this intervention is feasible and acceptable to both patients and clinicians. Although the sample size achieved in this study was small, findings suggest that the intervention may have a protective effect against declines in diet quality, and other health behaviours, in an older COPD population. Findings from this feasibility study indicate that further evaluation of the GENIE intervention is warranted in a larger study, with a longer follow-up. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02935452. NIH U.S. National Library of Medicine. Registered 17 October 2016.

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.

Impact of Rheumatoid Arthritis and Its Management on Falls, Fracture and Bone Mineral Density in UK Biobank.

Objectives: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease which presents with polyarthritis in addition to extra-articular manifestations. Historically, studies have shown a link between RA and adverse musculoskeletal outcomes but these studies were reported before the widespread use of biologic therapies. The aim of this study was therefore to investigate associations between RA, RA medications and bone mineral density, falls and fractures, using UK Biobank data. Methods: Diagnosis of RA was made using Hospital Episode Statistics (HES) ICD-10 coding. We assessed RA relationships with estimated bone mineral density (eBMD) from heel quantitative ultrasound measurements, self-reported falls (in last year) and HES recorded fracture, adjusted for age, ethnicity, BMI, smoking status, and physical activity. Results: Of 502,543 participants, 3849 (1.4%) of women and 1643 (0.7%) of men had a diagnosis of RA. Median age of the participants was 57 years (IQR 50-63) in women and 58 (IQR 50-64) in men. RA was associated with lower eBMD (men: ß -0.244, 95% CI -0.378, -0.110 p < 0.001; women: ß -0.217, 95% CI -0.297, -0.138 p < 0.001) a reported fall in the last year (men: OR 1.54, 95% CI 1.26, 1.87 p < 0.001; women: OR 1.36, 95% CI 1.19, 1.56 p < 0.001) and fracture in women (OR 1.76, 95% CI 1.43, 2.16 p < 0.001). Corticosteroid therapy in men (ß -0.934, 95% CI -1.565, -0.304 p = 0.004) and disease modifying anti-rheumatic drug (DMARD) use in both sexes (men: ß -0.437, 95% CI -0.761, -0.112 p = 0.008; women: ß -0.243, 95% CI -0.421, -0.065 p = 0.007), but not biologic therapy, were associated with a lower eBMD with RA. Conclusions: RA was associated with lower eBMD, increased falls and fracture. Corticosteroid and DMARD therapy, but not biologic therapy, were associated with lower eBMD.

Impact of osteoarthritis on activities of daily living: does joint site matter?

BACKGROUND: We consider the relationships between a clinical and radiological diagnosis of knee or hip OA and activities of daily-living (ADL) in older adults. METHODS: Data were available for 222 men and 221 women from the Hertfordshire Cohort Study (HCS) who also participated in the UK component of the European Project on Osteoarthritis (EPOSA). Participants completed the EuroQoL survey where they reported if they had difficulties with mobility, self-care, usual activities and movement around their house. Hip and knee radiographs were graded for overall Kellgren and Lawrence score (positive definition defined as a 2 or above). Clinical OA was defined using American College of Rheumatology criteria. RESULTS: In men, a clinical diagnosis of hip or knee OA were both associated with reported difficulties in mobility, ability to self-care and performing usual-activities (hip OA: OR 17.6, 95% CI 2.07, 149, p = 0.009; OR 12.5, 95% CI 2.51, 62.3, p = 0.002; OR 4.92, 95% CI 1.06, 22.8, p = 0.042 respectively. Knee OA: OR 8.18, 95% CI 3.32, 20.2, p < 0.001; OR 4.29, 95% CI 1.34, 13.7, p = 0.014; OR 5.32, 95% CI 2.26, 12.5, p < 0.001 respectively). Similar relationships were seen in women, where in addition, a radiological diagnosis of knee OA was associated with difficulties performing usual activities (OR 3.25, 95% CI 1.61, 6.54, p = 0.001). In general, men with OA reported stronger associations between moving around the house, specifically around the kitchen (clinical hip OA: OR 13.7, 95% CI 2.20, 85.6, p = 0.005; clinical knee OA OR 8.45, 95% CI 1.97, 36.2, p = 0.004) than women. DISCUSSION AND CONCLUSION: Clinical OA is strongly related to the ability to undertake ADL in older adults and should be considered in clinic consultations when seeing patients with OA.

Early-life predictors of future multi-morbidity: results from the Hertfordshire Cohort.

Background: multi-morbidity is an increasing challenge in western medicine and has the potential to impact patients' quality of life, treatment options and compliance with medications. The aim of this study was to identify the early-life predictors of long-term multi-morbidity in an historical cohort, the Hertfordshire Cohort Study (HCS). Methods: perinatal and infant health records were kept on all children born in Hertfordshire between 1931 and 1939. Participants who were still alive in 1998 were recruited to the HCS and data collected on major chronic diseases. They were subsequently followed up in the Clinical Outcomes Study (COS), and data recorded on all major illnesses since HCS, as well as current medications. Ordinal logistic regression analysed the association between early-life factors and the number of morbidities in these two surveys as well as medication count. Results: a total of 2299 participants had data in COS, 1131 (49%) were female, median age (interquartile range) at recruitment to HCS was 66 (64-68) years. Higher rates of childhood illnesses were significantly associated with future multi-morbidity (multivariate odds ratio (OR) (95% confidence interval (CI)) 1.15 (1.06, 1.25)) and higher medication counts at COS (multivariate OR (95%CI) 1.14 (1.06, 1.23)). Conclusions: children who experience more illnesses at a young age may be prone to develop multi-morbidity in later life.

Influences on diet quality in older age: the importance of social factors.

Background: poor diet quality is common among older people, but little is known about influences on food choice, including the role of psychosocial factors at this age. Objective: to identify psychosocial correlates of diet quality in a community-dwelling population of men and women aged 59-73 years; to describe relationships with change in diet quality over 10 years. Design: Longitudinal cohort, Hertfordshire Cohort Study (HCS). Subjects: HCS participants assessed at baseline (1998-2003: 1,048 men, 862 women); 183 men and 189 women re-assessed in 2011. Methods: diet was assessed by administered food frequency questionnaire; diet scores were calculated to describe diet quality at baseline and follow-up. A range of psychosocial factors (social support, social network, participation in leisure activities, depression and anxiety, sense of control) were assessed by questionnaire. Results: at baseline, better diet quality was related to a range of social factors, including increased confiding/emotional social support (men and women), practical support (men) and a larger social network (women) (all P < 0.05). For both men and women, greater participation in social and cognitive leisure activities was related to better diet quality (P < 0.005). There were few associations between measured psychosocial factors at baseline and change in diet score over 10 years, in the follow-up sub-group. However, greater participation in leisure activities, especially cognitive activities, at baseline was associated with smaller declines in diet quality over the 10-year follow-up period for both men (P = 0.017) and women (P = 0.014). Conclusions: in community-dwelling older adults, a range of social factors, that includes greater participation in leisure activities, were associated with diets of better quality.

Bone Microarchitecture in Men and Women with Diabetes: The Importance of Cortical Porosity.

High-resolution peripheral quantitative computed tomography (HR-pQCT) captures novel aspects of bone geometry, volumetric bone mineral density and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique to diabetic status are inconsistent in women and lacking in men. Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between bone microarchitecture from HR-pQCT of distal radius and distal tibia in 332 participants (177 men and 155 women) aged 72.1-81.4 years with or without diabetes mellitus (DM); n = 29 (18 men and 11 women) and n = 303, respectively. Statistical analyses were performed separately for women and men. The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. Participants with DM differed significantly in terms of weight in both women (70.4 ± 12.3 vs. 80.3 ± 18.3 kg; p = 0.015) and men (81.7 ± 11.4 vs. 92.8 ± 16.3 kg; p < 0.001) but no differences were found in height, smoking status, alcohol intake, social class and physical activity among women or men. Analyses in women revealed that cortical pore volume (Ct.Po.V) was higher in participants with DM and close to statistical significance for cortical porosity (Ct.Po) (ß = 0.76 [0.12, 1.41] z-score, p = 0.020 and ß = 0.62 [-0.02, 1.27] z-score, p = 0.059, respectively) at the distal radius. Adjustment for weight did not materially affect the relationship described for Ct.Po.V (ß = 0.74 [0.09, 1.39], p = 0.027) and Ct.Po (ß = 0.65 [-0.01, 1.30], p = 0.053) at the distal radius. After adjustment for weight, analyses in men revealed that Ct.Po and Ct.Po.V were higher in participants with DM (ß = 0.57 [0.09, 1.06] z-score, p = 0.021 and ß = 0.48 [0.01, 0.95] z-score, p = 0.044, respectively) at the distal tibia. Analyses of distal radial and tibial trabecular bone parameters according to diabetic status revealed no significant differences among men or women after adjustment for weight. We found higher cortical porosity and cortical pore volume at the distal tibia in men with DM and higher cortical pore volume at the distal radius in women with a non-significant tendency for higher cortical porosity. The results of our study suggest that deficits in cortical bone exist both in older men and women with DM.

Accumulation of risk factors associated with poor bone health in older adults.

UNLABELLED: Clustering of factors linked with poor bone health is common in older adults and is associated with lower bone density and increased fracture risk in women. PURPOSE: Many factors are associated with bone mineral density, which in turn is strongly linked with risk of fragility fracture. We assessed how commonly clustering of risk factors occurs and related such clustering to bone mineral density in a population of older community-dwelling men and women. METHOD: This is a cross-sectional study with 498 men and 498 women aged 59 to 72 years, who were participants in the Hertfordshire Cohort Study, in whom incident fracture was recorded. Physical activity, diet quality, history of prior fracture, family history of fracture, cigarette and alcohol consumption and comorbidities were obtained through baseline questionnaire. Measurements of grip strength and bone mineral density of the lumbar spine and total femur were also taken. RESULTS: Clustering of risk factors was common, with over 30% having two or more. In women, a graded association between the number of risk factors and low bone density was seen, and strong relationships were also seen between the number of risk factors and incident fracture; women with three or more risk factors had an adjusted hazard ratio (HR) of incident fracture of 5.98 (1.67, 21.43; p = 0.006) compared to women with no risk factors; women with two risk factors had an adjusted HR of 2.97 (1.14, 7.74; p = 0.03) and those with one, 2.28 (0.90, 5.75; p = 0.08). CONCLUSION: Clustering of risk factors for poor bone health is common in community-dwelling older adults and is associated with increased risk of fracture and adverse bone health in women.

Relationships between bone geometry, volumetric bone mineral density and bone microarchitecture of the distal radius and tibia with alcohol consumption.

PURPOSE: Chronic heavy alcohol consumption is associated with bone density loss and increased fracture risk, while low levels of alcohol consumption have been reported as beneficial in some studies. However, studies relating alcohol consumption to bone geometry, volumetric bone mineral density (vBMD) and bone microarchitecture, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), are lacking. METHODS: Here we report an analysis from the Hertfordshire Cohort Study, in which we studied associations between HR-pQCT measures at the distal radius and tibia and alcohol consumption in 376 participants (198 men and 178 women) aged 72.1-81.4 years. RESULTS: A total of 30 (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (<1 unit/week), low (≥1 unit/week and <11 units/week) and moderate/high (≥11 units/week) amounts of alcohol respectively. These figures were 74 (41.8%), 80 (45.2%) and 23 (13.0%) respectively in women for minimal/none (<1 unit/week), low (≥1 unit/week and <8 units/week) and moderate/high (≥8 units/week). At the distal radius, after adjustment for confounding factors (age, BMI, smoking status, dietary calcium intake, physical activity and socioeconomic status and years since menopause and HRT use for women), men that drank low alcohol had lower cortical thickness (p=0.038), cortical vBMD (p=0.033), and trabecular vBMD (p=0.028) and higher trabecular separation (p=0.043) than those that drank none/minimal alcohol. Similar differences were shown between minimal/none and moderate/high alcohol although these only reached statistical significance for the cortical parameters. Interestingly, after similar adjustment, women showed similar differences in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia. However, women that drank moderate/high alcohol had significantly higher trabecular vBMD (p=0.007), trabecular thickness (p=0.026), and trabecular number (p=0.042) and higher trabecular separation (p=0.026) at the distal radius than those that drank low alcohol. CONCLUSIONS: Our results suggest that alcohol consumption (low and moderate/high) may have a detrimental impact on bone health in men in both the cortical and trabecular compartments at the distal radius with similar results in women in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia suggesting that avoidance of alcohol may be beneficial for bone health.

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (ß = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (ß = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (ß per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (ß per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study. FUNDING: British Heart Foundation, UK Medical Research Council, and Academy of Finland.

Relationships between physical performance and knee and hip osteoarthritis: findings from the European Project on Osteoarthritis (EPOSA).

BACKGROUND: poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies. OBJECTIVE: to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries. METHODS: a total of 2,942 men and women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0-12); low PP was defined as a score of ≤9. RESULTS: the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain. CONCLUSION: lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites.