The impact of methods for estimating bone health and the global burden of bone disease

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

Fizičko opterećenje pri radu i osteoartroza kuka

The authors investigated the influence of physical strain at work on radiological signs of hip osteoarthritis. The study included 295 men and 298 women aged over 45 from an urban area who were classified in four groups according to physical demands of their occupation. The evaluation included clinical and radiological signs of hip osteoarthritis. The association between hip osteoarthritis and occupation was analysed using logistic regression. Though not significantly, radiological signs of hip osteoarthritis were common in subjects who worked in a standing position (odds 1.45 for men, 1.50 for women). Clinical signs of osteoarthritis in women were significantly associated with performance in a standing position (odds 3.00), whereas in men the association was more significant for jobs with high physical strain (odds 2.19). There was a sustained trend toward an increase in health risk with years of work in all job categories. Occupation did not appear to influence the development of radiological hiposteoarthritis, but the authors did establish association between clinical signs of hip osteoarthritis and work.U brojnim epidemiološkim istraživanjimaa procjenjivan je utjecaj zanimanja i fizičkog opterećenja na pojavu osteoartroze. U ovom istraživanju ispitivan je utjecaj fizičkog opterećenja vezanog uz zanimanje na pojavu osteoartroze kuka u gradskom stanovništvu. Istraživanjem je obuhvaćeno 295 muškaraca i 298 žena u gradu Zagrebu starijih od 45 godina. Prema fizičkom opterećenju vezanom uz zanimanje, ispitanici su bili podijeljeni u četiri kategorije. Učinjen je klinički i radiografski pregled desnog kuka. Osteoartrotske promjene stupnjevane su prema Kellgren-Lawrenceovoj metodi. Povezanost zanimanja i osteoartroze kuka analizirana je logističkom regresijom. Činilo se da su radiološki znakovi osteoartroze desnog kuka češći u osoba koje su pretežno radile u stojećem položaju, no to nije potvr|eno statistički (odds 1,45 za muškarce i 1,50 za žene). U žena, klinički znakovi osteoartroze, bol i ograničena rotacija, bili su značajno povezani sa stojećim zanimanjima. U muškaraca, klinički znakovi bolesti bili su značajno povezani i sa zanimanjima koja su obuhvaćala teže fizičke aktivnosti (odds 2,19). Analizom utjecaja duljine radnog staža na osteoartrozu kuka činilo se da postoji povećan rizik za razvoj osteoartroze kuka u osoba s duljim radnim vijekom u svim kategorijama zanimanja, no ta povezanost nije bila statistički značajna. Zaključeno je da u ispitivanom gradskom stanovništvu fizičko opterećenje vezano uz zanimanje nema značajan utjecaj na pojavu radioloških znakova osteoartroze kuka. Klinički znakovi osteoartroze kuka povezani su s fizičkim opterećenjem vezanim naročito uz zanimanja u stojećem položaju i ona s težim fizičkim opterećenjima

The gaps between patient and physician understanding of the emotional and physical impact of osteoporosis

Summary : A multinational survey was conducted to evaluate the gaps between patients and physicians understanding of osteoporosis. The International Osteoporosis Foundation recommends the creation of community-wide patient support programmes to increase prevention and treatment awareness of osteoporosis. Introduction: Osteoporosis is often undiagnosed and untreated, leaving millions of people at risk of debilitating fractures. A survey was designed to investigate any gaps that may exist between physician and patient knowledge of osteoporosis, understand barriers to patient adherence and identify ways to address unmet needs and improve communications. Methods: Telephone interviews were conducted with patients (n = 844) and physicians (n = 837) in 13 countries in June/July 2009. Patients were women with postmenopausal osteoporosis currently taking (or in the past 2years) prescribed medication. Physicians had experience in treating osteoporotic patients, which included only general practitioners who saw ≥10 (exception: in Hungary ≥5) and specialists who saw ≥20 patients with osteoporosis per month. Results: Physicians consistently underestimated their patients' adherence to treatment and beliefs on the impact of osteoporosis on their quality-of-life. Physicians underestimated how many patients worry about breaking a bone (51% vs 79%), as well as patient concerns about declines in activity levels (40% vs 70%), becoming dependent on others (30% vs 60%) and not being able to work for longer (30% vs 57%). Patients believed the most credible osteoporosis information was from specialists (94%). Patients (75%) would like easy to understand materials and 49% would welcome inter-patient discussions of their condition. Most physicians (88%) believed that osteoporosis organisations are among the most credible sources for information, 80% would give patients written materials to increase adherence and 76% would recommend patient programmes that encourage better communication on managing osteoporosis. Conclusion: Community-wide patient support programmes may help patients to manage their concerns and address unmet needs in osteoporosis managemen

Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults : research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO)

Introduction: Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects. Purpose and Methods: Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field. Results and conclusions: Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., 50 nmol/L, did not simultaneously assess multiple outcomes, and did not report overall safety (e.g., falls). Thus, no recommendations can be made to date for the use of vitamin D supplementation in general, parental compounds, or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases. Moreover, attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health cannot be recommended based on current evidence, since safety has yet to be confirmed. Finally, the promising findings from mechanistic studies, large cohort studies, and small clinical trials obtained for autoimmune diseases (including type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), cardiovascular disorders, and overall reduction in mortality require further confirmation

Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development

Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fa

DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years

Aims: Antisense non-coding RNA in the INK4 locus (ANRIL) fixed genetic variants have consistently been linked with coronary heart disease (CHD) risk. We investigated relationships between perinatal ANRIL promoter DNA methylation and CHD risk markers in children aged 9 years. Genetic variants in the non-coding RNA ANRIL identify it as an important CHD risk locus. Increasing evidence suggests that the early life environment may act through epigenetic processes to influence later CHD risk markers such as increased arterial pulse wave velocity (PWV, a measure of arterial stiffness) blood pressure or heart rate.Methods and results: Using pyrosequencing, ANRIL DNA methylation at nine CpG sites was measured in the umbilical cord from 144 children in a UK mother-offspring cohort and related to the descending aorta PWV measured by velocity-encoded phase contrast MRI at age 9 years. Perinatal methylation was not associated with child’s later blood pressure, but higher methylation at CpG5 was associated with increased childhood PWV (??=?0.066 m/s/10 % methylation increase [95 % CI, 0.004 to 0.128], p?=?0.037); 10 % decreases in methylation at CpG1 and CpG2 were associated with increased heart rate (CpG1 ??=?1.93 [0.07 to 3.8] beats/min, p?=?0.041; CpG2 ??=?2.30 [0.18 to 4.41] beats/min, p?=?0.033, accounting for potential confounding variables). The associations with perinatal ANRIL promoter methylation were independent of neighbouring fixed genetic variants.Conclusions: Our findings suggest developmental epigenetic regulation of ANRIL promoter methylation as a factor in later CHD risk in children.<br/

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

PurposeChronic 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.MethodsHere 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.ResultsA total of 30 (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (&lt; 1 unit/week), low (? 1 unit/week and &lt; 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 (&lt; 1 unit/week), low (? 1 unit/week and &lt; 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.ConclusionsOur 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.AbbreviationsaBMD, areal bone mineral density; BMI, body mass index; Ct. area, cortical area; Ct.vBMD, cortical density; Ct.Po, cortical porosity; Ct.Th, cortical thickness; DXA, dual energy X-ray absorptiometry; HCS, Hertfordshire Cohort Study; HRpQCT, high-resolution peripheral quantitative computed tomography; pQCT, peripheral quantitative computed tomography; Tt.area, total cross-sectional area; Tb.vBMD, trabecular BMD; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; vBMD, volumetric bone mineral density

Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts

Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) 5 to 10 years later. Data were drawn from five British cohorts participating in the Healthy Ageing across the Life Course research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10 % of a standard deviation (three studies, N = 3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing

Attitudes to ageing and change in frailty status:The English longitudinal study of ageing

Background: older people with more negative attitudes to ageing are at increased risk of several adverse outcomes, including decline in physical function and increased difficulties with activities of daily living. Objective: we investigated whether negative attitudes to ageing increase the risk of the onset or progression of frailty. Method: participants were 3,505 men and women aged 60 years and over from the English Longitudinal Study of Ageing. They completed a 12-item questionnaire on attitudes to ageing. Exploratory factor analysis was used to examine the structure of these items, and a single factor was derived which we labelled “physical and psychological loss.” Frailty was assessed by the Fried phenotype of physical frailty at waves 2 and 4, and by a frailty index at waves 2-5. Results: having a more positive attitude to ageing as regards “physical and psychological loss” was associated with a decreased risk of becoming physically frail or pre-frail at follow-up. For a standard deviation increment in score, the relative risk ratios (95% confidence interval), adjusted for age, sex and baseline level of physical frailty, were 0.86 (0.79, 0.94) for pre-frailty and 0.72 (0.63, 0.83) for frailty. Further adjustment for other potential confounding variables had only slight attenuating effects on these associations: multivariable-adjusted relative risk ratios were 0.89 (0.81, 0.98) for pre-frailty and 0.78 (0.68, 0.91) for frailty. Attitude to ageing was not associated with change in the frailty index over time after adjustment for potential confounding variables. Conclusion: older people who have a more positive attitude to ageing are at reduced risk of becoming physically frail or pre-frail. Future research needs to replicate this finding and discover the underlying mechanisms. Attitude to ageing was not a risk factor for change in the more broadly defined frailty index

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group

UNLABELLED: MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. BACKGROUND: Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. METHODS/DESIGN: Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. DISCUSSION: As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology