PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (162)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
more »
1.  Association of early childhood abdominal circumference and weight gain with blood pressure at 36 months of age: secondary analysis of data from a prospective cohort study 
BMJ Open  2014;4(7):e005412.
Objectives
To assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age.
Design
Analysis of data collected from a prospective cohort study.
Setting
Community-based investigation in Southampton, UK.
Participants
761 children with valid blood pressure measurements, born to women participating in the Southampton Women’s Survey.
Primary and secondary outcome measures
Anthropometric measurements were collected at 0, 6, 12, 24 and 36 months and conditional changes between the time points calculated. Blood pressure was measured at 36 months. Factors possibly influencing the blood pressure were assessed using linear regression. All independent variables of interest and confounding variables were included in stepwise multiple regression to identify the model that best predicted blood pressure at 36 months.
Results
Greater conditional gains in abdominal circumference (AC) between 0–6 and 24–36 months were associated with higher systolic and diastolic blood pressures at 36 months (p<0.001). Subscapular skinfold and height gains were weakly associated with higher blood pressures, while greater weight gains between 0–6, 12–24 and 24–36 months were more strongly associated, but the dominant influences were AC gains, particularly from 0–6 to 24–36 months. Thus one SD score increases in AC between 0–6 and 24–36 months were associated with 1.59 mm Hg (95% CI 0.97 to 2.21) and 1.84 mm Hg (1.24 to 2.46) higher systolic blood pressures, respectively, and 1.04 mm Hg (0.57 to 1.51) and 1.02 mm Hg (0.56, 1.48) higher diastolic pressures, respectively.
Conclusions
Conditional gains in abdominal circumference, particularly within 6 months of birth and in the year preceding measurement, were more positively associated with blood pressure at 36 months than gains in other anthropometric measures. Above-average AC gains in early childhood may contribute to adult hypertension and increased cardiovascular disease risk.
doi:10.1136/bmjopen-2014-005412
PMCID: PMC4091398  PMID: 24993768
EPIDEMIOLOGY
2.  Fracture prevention in patients with cognitive impairment presenting with a hip fracture: secondary analysis of data from the HORIZON Recurrent Fracture Randomised Controlled Trial 
PURPOSE
Patients with cognitive impairment (CI) are at high risk of fracture but often denied osteoporosis therapy. We tested whether the effects of zoledronic acid (Zol) on re-fracture and mortality differed in patients presenting with a hip fracture by cognitive status.
METHODS
We used data from the HORIZON Recurrent Fracture Trial, of yearly intravenous 5mg Zol vs. placebo in patients presenting with a hip fracture. Primary outcome was new fracture and secondary outcome mortality.
Short Portable Mental Status Questionnaire (SPMSQ) with a cut-point of >2 was used to identify CI. Fine-Gray models for competing events were fitted to study the effect of Zol on re-fracture and Cox regression for death. A multiplicative term was introduced to study a potential interaction between treatment and cognitive status on outcomes.
RESULTS
1,966/2,127 (92.4%) patients had baseline SPMSQ measured. 350 (17.8%) had CI, balanced between treatment arms. In the placebo arm, there was similar fracture incidence between those with and without CI (15.4% vs. 12.3%, p=0.26). There was no significant interaction for the effect of CI on Zol and re-fracture (p=0.66)). CI was associated with higher 1-year mortality (12.6% vs. 4.3%, p<0.001) and the interaction was bordering significance (interaction p=0.066). Zol prolonged survival only in patients with normal cognitive status (HR 0.56 [95%CI 0.40-0.80]) and not in those with CI (HR 0.90 [95%CI 0.59-1.38]).
CONCLUSIONS
While these results require confirmation, the findings support the use of bisphosphonates in patients with both osteoporotic fracture and CI expected to live for more than 6 months.
doi:10.1007/s00198-013-2420-8
PMCID: PMC3867338  PMID: 23812596
Fractures, Bone; Mortality; Zoledronic Acid; Dementia; Epidemiology
3.  Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women’s Survey 
The Journal of clinical endocrinology and metabolism  2013;99(1):10.1210/jc.2013-3241.
Context
Maternal 25-hydroxy-vitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function but little is known about a role for antenatal 25(OH)D exposure in programming muscle development.
Objective
We investigated the associations between maternal plasma 25(OH)D status at 34 weeks gestation and offspring lean mass and muscle strength at 4 years of age.
Design and setting
A prospective UK population-based mother-offspring cohort: the Southampton Women’s Survey (SWS).
Participants
12583 non-pregnant women were initially recruited into SWS, of which 3159 had singleton pregnancies. 678 mother-child pairs were included in this analysis.
Main Outcomes Measured
At 4 years of age, offspring assessments included hand grip strength (Jamar Dynamometer) and whole body DXA (Hologic Discovery) yielding lean mass and %lean mass. Physical activity was assessed by 7-day accelerometry (Actiheart) in a subset of children (n=326).
Results
Maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (β=0.10 SD/SD, p=0.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding and child’s physical activity at 4 years (β=0.13 SD/SD, p=0.014). Maternal 25(OH)D was also positively associated with offspring %lean mass (β=0.11 SD/SD, p=0.006), but not total lean mass (β=0.06, p=0.15). This however did not persist after adjustment for confounding factors (β=0.09 SD/SD, p=0.11).
Conclusions
This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than muscle mass.
doi:10.1210/jc.2013-3241
PMCID: PMC3880861  PMID: 24178796
vitamin D; grip strength; muscle mass; fetal programming
5.  Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management 
Rheumatology (Oxford, England)  2013;52(6):968-985.
A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.
doi:10.1093/rheumatology/ket007
PMCID: PMC3651616  PMID: 23445662
DXA; BMD; high bone mass; osteopetrosis; osteoarthritis
6.  Kidney Stones: A Fetal Origins Hypothesis† 
Kidney stones are common with a multifactorial aetiology involving dietary, environmental and genetic factors. In addition, patients with nephrolithiasis are at greater risk of hypertension, diabetes, metabolic syndrome, and osteoporosis although the basis for this is not fully understood. All of these renal stone associated conditions have also been linked with adverse early life events, including low birth weight, and it has been suggested that this developmental effect is due to excess exposure to maternal glucocorticoids in utero. This is proposed to result in long-term increased hypothalamic-pituitary-axis activation and there are mechanisms through which this effect could also promote urinary lithogenic potential. We therefore hypothesise that the association between renal stone disease and hypertension, diabetes, metabolic syndrome and osteoporosis may be related by a common pathway of programming in early life which, if validated, would implicate the developmental origins hypothesis in the aetiology of nephrolithiasis.
doi:10.1002/jbmr.1993
PMCID: PMC3792843  PMID: 23703881
Kidney Stones; Low Birth Weight; Fetal Origins; Osteoporosis; Metabolic Syndrome
7.  Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence 
Scientific Reports  2014;4:4705.
Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11–19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans.
doi:10.1038/srep04705
PMCID: PMC3989559  PMID: 24740086
8.  LOWER MATERNAL BODY CONDITION DURING PREGNANCY AFFECTS SKELETAL MUSCLE STRUCTURE AND GLUT-4 PROTEIN LEVELS BUT NOT GLUCOSE TOLERANCE IN MATURE ADULT SHEEP 
Sub-optimal maternal nutrition and body composition are implicated in metabolic disease risk in adult offspring. We hypothesized that modest disruption of glucose homeostasis previously observed in young adult sheep offspring from ewes of a lower body condition score (BCS) would deteriorate with age, due to changes in skeletal muscle structure and insulin signalling mechanisms. Ewes were fed to achieve a lower (L, n=10) or higher (H, n=14) BCS before and during pregnancy. Baseline plasma glucose, glucose tolerance and basal glucose uptake into isolated muscle strips was similar in male offspring at 210±4 weeks. Vastus total myofibre density (HBCS, 343±15; LBCS, 294±14 fibres/mm2, p<0.05) and fast myofibre density (HBCS, 226±10; LBCS 194±10 fibres/mm2, p<0.05), capillary to myofibre ratio (HBCS, 1.5±0.1; LBCS 1.2±0.1 capillary:myofibre, p<0.05) were lower in LBCS offspring. Vastus protein levels of Akt1 were lower (83±7% of HBCS, p<0.05), and total GLUT-4 was increased (157±6% of HBCS, p<0.001) in LBCS offspring, Despite the reduction in total myofibre density in LBCS offspring, glucose tolerance was normal in mature adult life. However such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment.
doi:10.1177/1933719113477494
PMCID: PMC3766346  PMID: 23420826
Glucose uptake; myofibres; type 2 diabetes; maternal body condition; skeletal muscle
9.  Liver fat accumulation is associated with reduced hepatic insulin extraction and beta cell dysfunction in healthy older individuals 
Background
There is a well-established association between type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of intrahepatic lipid (IHL), but the mechanistic basis for this association is unclear. Emerging evidence suggests that in addition to being associated with insulin resistance, NAFLD may be associated with relative beta-cell dysfunction. We sought to determine the influence of liver fat on hepatic insulin extraction and indices of beta-cell function in a cohort of apparently healthy older white adults.
Methods
We performed a cross-sectional analysis of 70 healthy participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3 ± 2.4 years) who underwent oral glucose tolerance testing with glucose, insulin and C-Peptide levels measured every 30 minutes over two hours. The areas under the concentration curve for glucose, insulin and C-Peptide were used to quantify hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral fat was quantified with magnetic resonance (MR) imaging and IHL with MR spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin Sensitivity (OGIS) model.
Results
29 of 70 participants (41%) exceeded our arbitrary threshold for NAFLD, i.e. IHL >5.5%. Compared to those with normal IHL, those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age, HbA1c and alanine aminotransferase (ALT) levels were similar in both groups. Insulin and C-Peptide excursions after oral glucose loading were higher in the NAFLD group, but the CGI and AI were significantly lower, indicating a relative defect in beta-cell function that is only apparent when C-Peptide is measured and when dynamic changes in glucose levels and also insulin sensitivity are taken into account. There was no difference in IGI or DI between the groups.
Conclusions
Although increased IHL was associated with greater insulin secretion, modelled parameters suggested relative beta-cell dysfunction with NAFLD in apparently healthy older adults, which may be obscured by reduced hepatic insulin extraction. Further studies quantifying pancreatic fat content directly and its influence on beta cell function are warranted.
Trial registration
ISRCTN60986572
doi:10.1186/1758-5996-6-43
PMCID: PMC3974597  PMID: 24669786
Adaptation index; Beta cell dysfunction; C-peptide-genic index; Disposition index; Hepatic insulin extraction; Insulinogenic index; Intrahepatic lipid; Non-alcoholic fatty liver disease
10.  Frailty and Fracture, Disability, and Falls: A Multiple Country Study from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 
Objectives
To test whether women age ≥ 55 years with increasing evidence of a frailty phenotype would have greater risk of fractures, disability, and recurrent falls, compared with women who were not frail, across geographic areas (Australia, Europe, and North America) and age groups.
Design
Multinational, longitudinal, observational cohort study.
Setting
The Global Longitudinal Study of Osteoporosis in Women (GLOW).
Participants
Women (n=48,636) age ≥ 55 years enrolled at sites in Australia, Europe, and North America.
Measurements
Components of frailty (slowness/weakness, poor endurance/exhaustion, physical activity, and unintentional weight loss) at baseline and report of fracture, disability, and recurrent falls at 1 year of follow-up were investigated. Women also reported health and demographic characteristics at baseline.
Results
Among those age < 75 years, women from the United States were more likely to be prefrail and frail than women from Australia/Canada, and Europe. The distribution of frailty was similar by region for women age ≥ 75 years. Odds ratios from multivariable models for frailty versus non frailty were 1.23 (95% CI = 1.07–1.42) for fracture, 2.29 (95% CI = 2.09–2.51) for disability, and 1.68 (95% CI = 1.54–1.83) for recurrent falls. The associations for pre-frailty versus non frailty were weaker but still indicated statistically significant increased risk for each outcome. Overall, associations between frailty status and each outcome were similar across age and geographic region.
Conclusion
Increased evidence of a frailty phenotype is associated with increased risk for fracture, disability, and falls among women age ≥ 55 years in 10 countries, with similar patterns across age and geographic region.
doi:10.1111/jgs.12146
PMCID: PMC3602412  PMID: 23351064
falls; fracture; frailty; osteoporosis; postmenopausal; women
11.  Programming of Osteoporosis and Impact on Osteoporosis Risk 
Osteoporosis is a skeletal disorder characterised by reduced bone quantity and quality and an increased susceptibility to fracture, and appears to be one of many chronic conditions that might be influenced by events early in life. Specifically, there is growing evidence of an interaction between the genome and the environment in the expression of the disease.
doi:10.1097/GRF.0b013e31829cb9b0
PMCID: PMC3732203  PMID: 23787708
osteoporosis; programming; bone; fracture; nutrition; cohort
14.  MATERNAL COTYLEDONS AT BIRTH PREDICT BLOOD PRESSURE IN CHILDHOOD 
Placenta  2013;34(8):672-675.
Introduction
A small placental surface at birth has been shown to be associated with the development of hypertension in later life. In this study we extend this observation by looking at the relationship between the number of placental cotyledons and blood pressure in childhood. Because the number of cotyledons is correlated with the surface area, we hypothesized that fewer cotyledons would be associated with higher blood pressure.
Methods
The Alspac study is a longitudinal study of 13,971 children born in Bristol. Their placentas were stored in formalin. We photographed the placentas of a sample of the children and related the number of maternal cotyledons to their blood pressure levels at age 9 years.
Results
Contrary to our hypothesis, a greater number of maternal cotyledons was associated with higher blood pressure. Among boys, a greater number of cotyledons was associated with higher systolic and diastolic pressure but not with higher pulse pressure. Diastolic pressure rose by 2.2 mmHg (95% CI 0.6 to 3.7, p =0.007) for every 10 additional cotyledons. Among girls, a greater number of cotyledons was associated with higher systolic pressure and pulse pressure but not with higher diastolic pressure. Pulse pressure rose by 2.7 mmHg (1.1 to 4.3, p<0.001) for every 10 additional cotyledons. These associations were little changed by adjustment for placental surface area.
Conclusion
Our study has shown that a large number of maternal cotyledons is associated with raised blood pressure in childhood. The associations differ in the two sexes.
doi:10.1016/j.placenta.2013.04.019
PMCID: PMC3733167  PMID: 23731799
Alspac; maternal cotyledons; blood pressure
15.  Quality of Life in Sarcopenia and Frailty 
Calcified tissue international  2013;93(2):101-120.
The reduced muscle mass and impaired muscle performance that defines sarcopenia in older individuals is associated with increased risk of physical limitation and a variety of chronic diseases. It may also contribute to clinical frailty.
A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities.
This review and report of an expert meeting, presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarises QoL concepts and specificities in older populations, examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability and argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade off study could be appropriate.
doi:10.1007/s00223-013-9758-y
PMCID: PMC3747610  PMID: 23828275
Age; aging; muscle weakness; quality of life; malnutrition
17.  Objectively measured physical activity in four-year-old British children: a cross-sectional analysis of activity patterns segmented across the day 
Background
Little is known about preschool-aged children’s levels of physical activity (PA) over the course of the day. Using time-stamped data, we describe the levels and patterns of PA in a population-based sample of four-year-old British children.
Methods
Within the Southampton Women’s Survey the PA levels of 593 4-year-old children (51% female) were measured using (Actiheart) accelerometry for up to 7 days. Three outcome measures: minutes spent sedentary (<20 cpm); in light (LPA: ≥20 – 399 cpm) and in moderate-to-vigorous activity (MVPA: ≥400 cpm) were derived. Average daily activity levels were calculated and then segmented across the day (morning, afternoon and evening). MVPA was log-transformed. Two-level random intercept models were used to analyse associations between activity level and temporal and demographic factors.
Results
Children were active for 67% (mean 568.5 SD 79.5 minutes) of their daily registered time on average, with 88% of active time spent in LPA. All children met current UK guidelines of 180 minutes of daily activity. There were no differences in children’s average daily levels of sedentary activity and LPA by temporal and demographic factors: differences did emerge when activity was segmented across the day. Sex differences were largest in the morning, with girls being more sedentary, spending fewer minutes in LPA and 18% less time in MVPA than boys. Children were more sedentary and less active (LPA and MVPA) in the morning if they attended childcare full-time compared to part-time, and on weekend mornings compared to weekdays. The reverse was true for weekend afternoons and evenings. Children with more educated mothers were less active in the evenings. Children were less sedentary and did more MVPA on summer evenings compared to winter evenings.
Conclusions
Preschool-aged children meet current physical activity guidelines, but with the majority of their active time spent in LPA, investigation of the importance of activity intensity in younger children is needed. Activity levels over the day differed by demographic and temporal factors, highlighting the need to consider temporality in future interventions. Increasing girls’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile.
doi:10.1186/1479-5868-11-1
PMCID: PMC3896827  PMID: 24405936
18.  Health technology assessment in osteoporosis 
We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of healthcare resources by decision-makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting, and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society with lifetime risks of any fracture of the hip, spine and forearm of around 40% for women and 13% for men. The economic impact is also large, for example, Europe’s six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision-makers in healthcare on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce healthcare resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision-makers efficiently allocate healthcare resources.
doi:10.1007/s00223-013-9724-8
PMCID: PMC3696176  PMID: 23515633
Burden of disease; cost-effectiveness; economic evaluation; health technology assessment; osteoporosis
19.  Fetal and infant growth predict hip geometry at six years old: Findings from the Southampton Women’s Survey 
Pediatric research  2013;74(4):450-456.
Background
We investigated relationships between early growth and proximal femoral geometry at age six years in a prospective population-based cohort, the Southampton Women’s Survey.
Methods
In 493 mother-offspring pairs we assessed linear size (individual measure dependent on developmental stage) using high-resolution ultrasound at 11, 19 and 34 weeks gestation (femur length) and at birth, 1, 2, 3, 4 and 6 years (crown-heel length/height). Standard deviation (SD)-scores were created and conditional regression modelling generated mutually independent growth variables. Children underwent hip DXA (Dual X-ray absorptiometry) at 6 years (Hologic Discovery, Hologic Inc., MA); hip structure analysis software yielded measures of geometry and strength.
Results
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 years, with the strongest relationships observed for femur growth from 19-34 weeks gestation (β=0.26 cm3/SD, p<0.0001), and for height growth from birth to 1 year (β=0.25 cm3/SD, p<0.0001) and 1-2 years (β=0.33 cm3/SD, p<0.0001), with progressively weaker relationships over years 3 (β=0.23 cm3/SD, p=0.0002) and 4 (β=0.10 cm3/SD, p=0.18).
Conclusions
These results demonstrate that growth before age 3 years predicts proximal femoral geometry at six years old. The data suggest critical periods in which there is capacity for long term influence on the later skeletal growth trajectory.
doi:10.1038/pr.2013.119
PMCID: PMC3797011  PMID: 23857297
20.  When, Where and How Osteoporosis-Associated Fractures Occur: An Analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 
PLoS ONE  2013;8(12):e83306.
Objective
To examine when, where and how fractures occur in postmenopausal women.
Methods
We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.
Results
Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.
Conclusion
In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
doi:10.1371/journal.pone.0083306
PMCID: PMC3859637  PMID: 24349484
21.  Inflammatory markers and incident frailty in men and women: The English Longitudinal Study of Ageing 
Age (Dordrecht, Netherlands)  2013;35(6):10.1007/s11357-013-9528-9.
Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein and fibrinogen and risk of incident frailty in 2146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between C-reactive protein and fibrinogen and risk of incident frailty differed significantly by sex (p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation increase in c-reactive protein or fibrinogen odds ratios (95% confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72) respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen the fully-adjusted odds ratio (95% confidence interval) for incident frailty in women was 1.27 (0.96, 1.69 and 1.31 (1.04, 1.67) respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers C-reactive protein and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference.
doi:10.1007/s11357-013-9528-9
PMCID: PMC3751755  PMID: 23543263
frailty; inflammation; C-reactive protein; fibrinogen; longitudinal study
22.  How to define responders in osteoarthritis 
Background
Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures.
Scope
Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis.
Findings
The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement.
Conclusion
The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process.
doi:10.1185/03007995.2013.792793
PMCID: PMC3690437  PMID: 23557069
magnetic resonance imaging; osteoarthritis; X-ray; responder; structure-modifying drug; pain
24.  Using natural experiments to evaluate population health interventions: new MRC guidance 
Natural experimental studies are often recommended as a way of understanding the health impact of policies and other large scale interventions. Although they have certain advantages over planned experiments, and may be the only option when it is impossible to manipulate exposure to the intervention, natural experimental studies are more susceptible to bias. This paper introduces new guidance from the Medical Research Council to help researchers and users, funders and publishers of research evidence make the best use of natural experimental approaches to evaluating population health interventions. The guidance emphasises that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear. However, a good understanding is needed of the process determining exposure to the intervention, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital. More could be learnt from natural experiments in future as experience of promising but lesser used methods accumulates.
doi:10.1136/jech-2011-200375
PMCID: PMC3796763  PMID: 22577181
25.  Different Indices of Fetal Growth Predict Bone Size and Volumetric Density at 4 Years of Age 
We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.
doi:10.1359/jbmr.091022
PMCID: PMC3793299  PMID: 20437610
EPIDEMIOLOGY; OSTEOPOROSIS; PROGRAMMING; DEVELOPMENTAL ORIGINS

Results 1-25 (162)