Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 772
Filtrar
1.
Bone ; 147: 115937, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766802

RESUMO

BACKGROUND: Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. METHODS: 115 males and 99 females (aged 72-81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011-2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011-2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. RESULTS: Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). CONCLUSION: Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

2.
BMC Public Health ; 21(1): 574, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757464

RESUMO

BACKGROUND: Loneliness is an important public health issue associated with mortality and morbidity. Often researched amongst older people, less is known about risk factors for loneliness among adults aged 50-64 years who are in work. We investigated (a) if exit from the workforce increases the odds of loneliness; (b) whether adverse psychosocial work factors are associated with increased odds of loneliness over 2 years of follow-up; and (c) whether the association is stronger among subjects still working compared with those who have exited the workforce. METHODS: Data came from the Health and Employment After Fifty (HEAF) study, a large population cohort who provided questionnaire information about work and health at baseline and 2 annual follow-ups. Logistic regression was used to explore the association between psychosocial risk factors and loneliness at follow-up 2, with adjustment for loneliness at baseline, sex, age, self-rated health, living alone, and mental health diagnosis. RESULTS: Of the initial 8134 participants, 4521 were working at baseline and provided data for this analysis. Of those, 507 (11.2%) were defined as lonely at 2 years' follow-up. Exiting the workforce was not significantly associated with loneliness (OR = 1.1, 95%CI: 0.7-1.7). However, negative psychosocial work factors predicted loneliness at follow-up. After mutual adjustment, lack of choice at work (OR: 1.5, 95%CI: 1.1-1.9), often lying awake worrying about work (OR: 1.4, 95%CI: 1.0-1.9) and perceived not coping with physical demands of the job (OR: 1.3, 95%CI: 1.0-1.7) were independent predictors, with associations robust to adjustment for demographic factors and health. Associations were only slightly altered when we restricted the sample to those who remained in work until the end of follow-up. CONCLUSIONS: Loneliness amongst middle-aged working adults is not predicted by permanent work exit but is predicted by individuals' perceptions about their work. Provision of good-quality work, matched to the capacity of the older worker, could prevent loneliness.

3.
Epigenetics ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784941

RESUMO

Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at both the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human MethylationEPIC array we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p≤6.45x10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195g (95%CI: -241, -149g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin releasing hormone binding protein (CRHBP).. Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p=1.37x10-255), maternal smoking (7.71%, p=1.50x10-57) and maternal plasma folate levels during pregnancy (0.33%, p=0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and/or suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.

4.
Health Technol Assess ; 25(17): 1-106, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33739919

RESUMO

BACKGROUND: Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects. OBJECTIVES: The aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time. DESIGN: This was a new-user cohort study design with propensity score matching. SETTING AND DATA SOURCES: Data were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1-3 and from the Danish Odense University Hospital Databases for work package 4. PARTICIPANTS: Patients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m2 were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m2 within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1-3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1-4. INTERVENTIONS/EXPOSURE: Bisphosphonate use, identified from primary care prescriptions (for work packages 1-3) or pharmacy dispensations (for work package 4), was the main exposure. MAIN OUTCOME MEASURES: Work package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change. RESULTS: Bisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users. LIMITATIONS: Confounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively. CONCLUSIONS: Bisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness. FUTURE WORK: Randomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data. STUDY REGISTRATION: This study is registered as EUPAS10029. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 17. See the NIHR Journals Library website for further project information. The project was also supported by the National Institute for Health Research Biomedical Research Centre, Oxford.

5.
Aging Clin Exp Res ; 33(3): 479-494, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33565045

RESUMO

Calcium, magnesium and strontium have all been implicated in both musculoskeletal and cardiovascular health and disease. However, despite these three elements being closely chemically related, there is marked heterogeneity of their characteristics in relation to cardiovascular outcomes. In this narrative review, we describe the relevant evidential landscape, focusing on clinical trials where possible and incorporating findings from observational and causal analyses, to discern the relative roles of these elements in musculoskeletal and cardiovascular health. We conclude that calcium supplementation (for bone health) is most appropriately used in combination with vitamin D supplementation and targeted to those who are deficient in these nutrients, or in combination with antiosteoporosis medications. Whilst calcium supplementation is associated with gastrointestinal side effects and a small increased risk of renal stones, purported links with cardiovascular outcomes remain unconvincing. In normal physiology, no mechanism for an association has been elucidated and other considerations such as dose response and temporal relationships do not support a causal relationship. There is little evidence to support routine magnesium supplementation for musculoskeletal outcomes; greater dietary intake and serum concentrations appear protective against cardiovascular events. Strontium ranelate, which is now available again as a generic medication, has clear anti-fracture efficacy but is associated with an increased risk of thromboembolic disease. Whilst a signal for increased risk of myocardial infarction has been detected in some studies, this is not supported by wider analyses. Strontium ranelate, under its current licence, thus provides a useful therapeutic option for severe osteoporosis in those who do not have cardiovascular risk factors.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Cálcio , Feminino , Humanos , Magnésio , Osteoporose/tratamento farmacológico , Estrôncio/efeitos adversos
6.
Aging Clin Exp Res ; 33(3): 529-545, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33590469

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.


Assuntos
Doenças Cardiovasculares , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia
7.
BMC Med ; 19(1): 33, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33612114

RESUMO

BACKGROUND: Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. METHODS: We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. RESULTS: The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively]. These associations were robust in several sensitivity analyses and further adjustment for birth weight and childhood diet did not meaningfully alter the associations and conclusions. In two cohorts with available data, a higher whole pregnancy E-DII and lower DASH scores were associated with a lower late-childhood FFMI in males and a higher mid-childhood FMI in females (P interactions < 0.10). CONCLUSIONS: A pro-inflammatory, low-quality maternal antenatal diet may adversely influence offspring body composition and OWOB risk, especially during late-childhood. Promoting an overall healthy and anti-inflammatory maternal dietary pattern may contribute to the prevention of childhood obesity, a complex health issue requiring multifaceted strategy.

8.
Qual Life Res ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595825

RESUMO

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.

9.
PLoS Med ; 18(1): e1003491, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33476335

RESUMO

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. METHODS AND FINDINGS: We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [ß(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [ß(95% CI) = -18.7(-34.8, -2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [-0.07(-0.14, -0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [-0.06(-0.10, -0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. CONCLUSIONS: In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

10.
Health Technol Assess ; 25(5): 1-72, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33501902

RESUMO

BACKGROUND: Chronic pain is a common cause of health-related incapacity for work among people in the UK. Individualised placement and support is a systematic approach to rehabilitation, with emphasis on early supported work placement. It is effective in helping people with severe mental illness to gain employment, but has not been tested for chronic pain. OBJECTIVE: To inform the design of a definitive randomised controlled trial to assess the clinical effectiveness of individualised placement and support for people unemployed because of chronic pain. METHODS: A mixed-methods feasibility study comprising qualitative interviews and focus groups with key stakeholders, alongside a pilot trial. STUDY PARTICIPANTS: Primary care-based health-care professionals, employment support workers, employers, clients who participated in an individualised placement and support programme, and individuals aged 18-64 years with chronic pain who were unemployed for at least 3 months. INTERVENTION: An individualised placement and support programme integrated with a personalised, responsive pain management plan, backed up by communication with a general practitioner and rapid access to community-based pain services. OUTCOMES: Outcomes included stakeholder views about a trial and methods of recruitment; the feasibility and acceptability of the individualised placement and support intervention; study processes (including methods to recruit participants from primary care, training and support needs of the employment support workers to integrate with pain services, acceptability of randomisation and the treatment-as-usual comparator); and scoping of outcome measures for a definitive trial. RESULTS: All stakeholders viewed a trial as feasible and important, and saw the relevance of employment interventions in this group. Using all suggested methods, recruitment was feasible through primary care, but it was slow and resource intensive. Recruitment through pain services was more efficient. Fifty people with chronic pain were recruited (37 from primary care and 13 from pain services). Randomisation was acceptable, and 22 participants were allocated to individualised placement and support, and 28 participants were allocated to treatment as usual. Treatment as usual was found acceptable. Retention of treatment-as-usual participants was acceptable throughout the 12 months. However, follow-up of individualised placement and support recipients using postal questionnaires proved challenging, especially when the participant started paid work, and new approaches would be needed for a trial. Clients, employment support workers, primary care-based health-care professionals and employers contributed to manualisation of the intervention. No adverse events were reported. CONCLUSION: Unless accurate and up-to-date employment status information can be collected in primary care health records, or linkage can be established with employment records, research such as this relating to employment will be impracticable in primary care. The trial may be possible through pain services; however, clients may differ. Retention of participants proved challenging and methods for achieving this would need to be developed. The intervention has been manualised. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30094062. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 5. See the NIHR Journals Library website for further project information.

11.
J Bone Miner Res ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33450071

RESUMO

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX® ) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2 ) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height2 , depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

12.
Bone ; 144: 115833, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33359889

RESUMO

Despite substantial advances in delineation of the epidemiology, pathophysiology, risk assessment and treatment of osteoporosis over the last three decades, a substantial proportion of men and women at high risk of fracture remain untreated - the so-called "treatment gap". This review summarises the important patient-, physician- and policyrelated causes of this treatment gap, before discussing in greater detail: (a) the evidence base for the efficacy of bisphosphonates in osteoporosis; (b) recent evidence relating to the adverse effects of this widely used therapeutic class, most notably atypical femoral fracture and osteonecrosis of the jaw; (c) available strategies to improve both secondary and primary prevention pathways for the management of this disorder.

13.
Clin Chim Acta ; 515: 16-20, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33382995

RESUMO

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and ß-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of ß-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and ß-CTX.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33276373

RESUMO

The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. Osteoporosis describes low bone mass and deterioration of the micro-architecture of the bone, whereas sarcopenia is the loss of muscle mass, strength and function. With an ageing population the prevalence of both conditions is likely to increase substantially over the coming decades and is associated with significant personal and societal burden. The sequelae for an individual suffering from both conditions together include a greater risk of falls, fractures, institutionalization and mortality. The aetiology of 'osteosarcopenia' is multifactorial with several factors linking muscle and bone function, including genetics, age, inflammation and obesity. Several biochemical pathways have been identified that are facilitating the development of several promising therapeutic agents, which target both muscle and bone. In the current review we outline the epidemiology, pathogenesis and clinical consequences of 'osteosarcopenia' and explore current and potential future management strategies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33331900

RESUMO

OBJECTIVES: X-Linked hypophosphataemic rickets (XLH) is a rare multisystemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls. METHODS: The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995-2016), along with a non-XLH cohort matched (1:4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to Index of Multiple Deprivation (IMD). RESULTS: There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine (OR 3.46 [95% CI: 1.44-8.31]) and neurological (OR 3.01 [95% CI: 1.41-6.44] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 [95%CI: 1.47-5.92]. Distribution of IMD among XLH cases indicated greater deprivation than the general population. CONCLUSION: We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients.

16.
J Bone Miner Res ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373491

RESUMO

Bisphosphonates are the first-line treatment for preventing fractures in osteoporosis patients. However, their use is contraindicated or to be used with caution in chronic kidney disease (CKD) patients, primarily because of a lack of information about their safety and effectiveness. We aimed to investigate the safety of oral bisphosphonates in patients with moderate to severe CKD, using primary-care electronic records from two cohorts, CPRD GOLD (1997-2016) and SIDIAP (2007-2015) in the UK and Catalonia, respectively. Both databases were linked to hospital records. SIDIAP was also linked to end-stage renal disease registry data. Patients with CKD stages 3b to 5, based on two or more estimated glomerular filtration rate measurements less than 45 mL/min/1.73 m2 , aged 40 years or older were identified. New bisphosphonate users were propensity score-matched with up to five non-users to minimize confounding within this population. Our primary outcome was CKD stage worsening (estimated glomerular filtration rate [eGFR] decline or renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers, and severe hypocalcemia. Hazard ratios (HRs) were estimated using Cox regression and Fine and Gray sub-HRs were calculated for competing risks. We matched 2447 bisphosphonate users with 8931 non-users from CPRD and 1399 users with 6547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in CPRD (sub-HR [95% CI]: 1.14 [1.04, 1.26]) and SIDIAP (sub-HR: 1.15 [1.04, 1.27]). No risk differences were found for acute kidney injury, gastrointestinal bleeding/ulcers, or hypocalcemia. Hence, we can conclude a modest (15%) increased risk of CKD progression was identified in association with bisphosphonate use. No other safety concerns were identified. Our findings should be considered before prescribing bisphosphonates to patients with moderate to severe CKD. © 2020 American Society for Bone and Mineral Research (ASBMR).

17.
Sleep Health ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33223446

RESUMO

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.

18.
Calcif Tissue Int ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191483

RESUMO

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70-79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2-3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10-14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p < 0.05) with increased rates of mortality; fully-adjusted hazard ratios per SD lower gait speed and grip strength were 1.27 (95% CI 1.19, 1.36) and 1.14 (1.07, 1.21), respectively. Risk factors of hospital admission included lower levels and greater declines in gait speed and grip strength, and greater declines in hip BMD. Lower levels and greater declines in fat mass and hip BMD were associated with low trauma fracture. Lower gait speed, higher fat mass, and both lower levels and greater declines in grip strength were related to recurrent falls. Lower baseline levels and greater declines in musculoskeletal parameters were related to adverse outcomes. Interventions to maximize peak levels in earlier life and reduce rates of age-related decline may reduce the burden of disease in this age group.

19.
Curr Osteoporos Rep ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200372

RESUMO

PURPOSE OF THE REVIEW: The aim of this review is to briefly introduce updates in global fracture epidemiology and then to highlight recent contributions to understanding ethnic differences in bone density, geometry and microarchitecture and consider how these might contribute to differences in fracture risk. The review focuses on studies using peripheral quantitative computed tomography techniques. RECENT FINDINGS: Recent studies have contributed to our understanding of the differences in fracture incidence both between countries, as well as between ethnic groups living within the same country. In terms of understanding the reasons for ethnic differences in fracture incidence, advanced imaging techniques continue to increase our understanding, though there remain relatively few studies. It is a priority to continue to understand the epidemiology, and changes in the patterns of, fracture, as well as the underlying phenotypic and biological reasons for the ethnic differences which are observed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33143153

RESUMO

Maternal smoking during pregnancy has established associations with poor perinatal outcomes. Among continuing pregnant smokers, harm-reduction strategies have been suggested, including temporary cessation of smoking during pregnancy, also known as partial quitting. Support for this strategy, however, remains limited. Six hundred and ninety-seven women in the Southampton Women's Survey who smoked at their last menstrual period were categorised into sustained quitters, partial quitters (quit in either the first or third trimester but not both) or sustained smokers (continued to smoke throughout pregnancy). In regression models, compared with infants born to sustained smokers, infants born to sustained quitters and partial quitters were heavier at birth by ß = 0.64 standard deviations (SD) (WHO z-score) (95% CI: 0.47-0.80) and 0.48 SD (WHO z-score) (95% CI: 0.24-0.72) respectively, adjusted for confounders, with similar patterns seen for other anthropometric measures (head circumference and crown-heel length). Sustained quitters had longer gestations by ß = 3.5 days (95% CI: 1.8-5.2) compared with sustained smokers, but no difference was seen for partial quitters. While sustained quitting remains the most desired outcome for pregnant smokers, partial quitting should be explored as a strategy to reduce some of the harmful effects of smoking on offspring in those who cannot achieve sustained quitting.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...