A Healthy Conversation Skills intervention to support changes to physical activity and dietary behaviours in community-dwelling older adults during the COVID-19 pandemic.

AIMS: Physical activity (PA) and nutrition are important determinants of health in late adulthood. However, low levels of PA and poor nutrition are common in older adults and have become more prevalent during the COVID-19 pandemic. We hypothesised that Healthy Conversation Skills could be used to support health behaviour changes beneficial for health in older adults and thus conducted a study nested within the UK Hertfordshire Cohort Study. METHODS: Between November 2019 and March 2020, 176 participants were visited at home. A trained researcher administered a questionnaire and undertook anthropometric and physical performance tests. A total of 89 participants were randomised to the control group and received a healthy living leaflet; 87 participants in the intervention group were interviewed using Healthy Conversation Skills at the initial visit with follow-up telephone calls at 1, 3, 6 and 9 months. Follow-up at 1 year by postal questionnaire assessed change in PA and diet. In total, 155 participants (79 control and 76 intervention) completed the baseline and 1-year follow-up. RESULTS: At baseline, median (lower quartile, upper quartile) age (years) was 83.1 (81.5, 85.5) and median PA time (min/day) from walking, cycling and sports was 30.0 (15.0, 60.0). In total, 95% of participants completed the intervention; the total response rate for postal questionnaires was 94%. There were no statistically significant differences in outcomes between the trial arms. In women, there was a tendency for greater increases in diet quality in the intervention group compared to the control group (p = 0.075), while among men, there was a tendency for reduced decline in self-reported physical function in the intervention group compared to the control group (p = 0.081). CONCLUSION: We have shown that it is viable to utilise Healthy Conversation Skills via telephone to promote healthier lifestyles in older adults. Larger appropriately powered studies to determine the efficacy of such an intervention are now warranted.

COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants.

BACKGROUND: Frailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease. AIMS: We investigated, in the UK Biobank, whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19. METHODS: 502,640 participants aged 40-69 years at baseline (54-79 years at COVID-19 testing) were recruited across UK during 2006-10. A modified assessment of frailty using Fried's classification was generated from baseline data. COVID-19 test results (England) were available for 16/03/2020-01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, after adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups. RESULTS: 4510 participants were tested for COVID-19 (positive = 1326, negative = 3184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR = 1.4 [95%CI = 1.1, 1.8]), report slow walking speed (OR = 1.3 [1.1, 1.6]), report two or more falls in the past year (OR = 1.3 [1.0, 1.5]) and be multimorbid (≥ 4 comorbidity groupings vs 0-1: OR = 1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. However, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants. DISCUSSION AND CONCLUSIONS: Frailty and multimorbidity do not appear to aid risk stratification, in terms of positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Infant milk feeding and bone health in later life: findings from the Hertfordshire cohort study.

Using data from the Hertfordshire cohort study, this study examined the effect of breastfeeding and bottle feeding on adult lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD). The type of infant milk feeding was significantly associated with lumbar spine BMD in males. INTRODUCTION: Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD. METHODS: Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score. RESULTS: Infant milk feeding was significantly associated with lumbar spine BMD (b = - 0.028; 95% CI, - 0.055; - 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females. CONCLUSIONS: Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS).

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited. INTRODUCTION: In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015. METHODS: Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers. RESULTS: The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, ß-hydroxy-ß-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs). CONCLUSION: Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.

Lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with bone microstructure abnormalities in women.

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius. INTRODUCTION: Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters. RESULTS: The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n = 83) vs. 17.3 % (n = 28), p < 0.001). After adjustment for confounding factors, we found that women with LLAC had substantially lower Ct.area (ß = -0.33, p = 0.016), lower Tb.N (ß = -0.54, p = 0.013) and higher Tb.Sp (ß = 0.54, p = 0.012) at the distal tibia and lower Tb.Th (ß = -0.49, p = 0.027) at the distal radius compared with participants without LLAC. Distal radial or tibial bone parameter analyses in men according to their LLAC status revealed no significant differences with the exception of Tb.N (ß = 0.27, p = 0.035) at the distal tibia. CONCLUSION: In the HCS, the presence of LLAC assessed by HR-pQCT was associated with relevant bone microstructure abnormalities in women. These findings need to be replicated and further research should study possible pathophysiological links between vascular calcification and osteoporosis.

Ischemic heart disease is associated with lower cortical volumetric bone mineral density of distal radius.

UNLABELLED: In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate geometric, volumetric and microstructural parameters at the distal radius and at the distal tibia in participants with ischaemic heart disease. We found that, compared with participants without ischaemic heart disease, they had substantially lower cortical volumetric bone mineral density (BMD) at the distal radius. INTRODUCTION: HR-pQCT captures novel aspects of bone geometry and volumetric bone mineral density (vBMD) and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique in patients with ischemic heart disease (IHD) are lacking. METHODS: Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from HR-pQCT of distal radius and distal tibia in 350 participants (184 men and 166 women) aged 71.5-80.5 years with or without IHD (e.g. heart attack, angina or heart failure; n = 75 and n = 275, respectively). RESULTS: Analyses for all participants (men and women together) revealed that cortical vBMD (Ct.vBMD) was lower (p < 0.001) and cortical thickness (Ct.th) was not different (p = 0.519), whereas cortical porosity (Ct.Po) was higher (p = 0.016) in participants with IHD at the distal radius. Moreover, trabecular microarchitectural parameters were not significantly different in patients with IHD (p > 0.05 for all). Adjustment for a priori confounders (age, gender, body mass index, smoking status, alcohol consumption, high blood pressure and diabetes mellitus) did not materially affect the relationship described for Ct.vBMD (p = 0.002), but differences in Ct.Po were attenuated. Analyses in men alone revealed that only Ct.vBMD was lower at the distal radius in participants with IHD with and without adjustment for a priori confounders (p = 0.0002 and p = 0.004, respectively), whereas no statistical differences were found in women, although patterns of differences were similar in both sexes. Moreover, no association was found between IHD and bone parameters at the distal tibia either in men or women. CONCLUSIONS: We have demonstrated that IHD is associated with lower Ct.vBMD of the distal radius.

Peripheral quantitative computed tomography measures are associated with adult fracture risk: the Hertfordshire Cohort Study.

Peripheral quantitative computed tomography (pQCT) captures novel aspects of bone geometry that may contribute to fracture risk and offers the ability to measure both volumetric bone mineral density (vBMD) and a separation of trabecular and cortical compartments of bone, but longitudinal data relating measures obtained from this technique to incident fractures are lacking. Here we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from pQCT and DXA in 182 men and 202 women aged 60-75 years at baseline with incident fractures over 6 years later. Among women, radial cortical thickness (HR 1.72, 95% CI 1.16, 2.54, p=0.007) and cortical area (HR 1.91, 95% CI 1.27, 2.85, p=0.002) at the 66% slice were both associated with incident fractures; these results remained significant after adjustment for confounders (age, BMI, social class, cigarette smoking and alcohol consumption, physical activity, dietary calcium, HRT and years since menopause). Further adjustment for aBMD made a little difference to the results. At the tibia, cortical area (HR 1.58, 95% CI 1.10, 2.28, p=0.01), thickness (HR 1.49, 95% CI 1.08, 2.07, p=0.02) and density (HR 1.64, 95% CI 1.18, 2.26, p=0.003) at the 38% site were all associated with incident fractures with the cortical area and density relationships remaining robust to adjustment for the confounders listed above. Further adjustment for aBMD at this site did lead to attenuation of relationships. Among men, tibial stress-strain index (SSI) was predictive of incident fractures (HR 2.30, 95% CI 1.28, 4.13, p=0.005). Adjustment for confounding variables and aBMD did not render this association non-significant. In conclusion, we have demonstrated relationships between measures of bone size, density and strength obtained by pQCT and incident fracture. These relationships were attenuated but in some cases remained significant after adjustment for BMD measures obtained by DXA, suggesting that some additional information may be conferred by this assessment.

Exposure to heavy physical occupational activities during working life and bone mineral density at the hip at retirement age.

BACKGROUND: People in sedentary occupations are at increased risk of hip fracture. Hip fracture is significantly associated with low bone mineral density (BMD) measured at the hip. Physical activity is important in the development and maintenance of BMD, but the effects of occupational physical activity on bone health are unclear. We investigated the influence of lifetime physical activity on BMD at the hip. METHODS: This was a cross-sectional epidemiological study of the associations between total hip BMD measured by dual-energy X-ray absorptiometry at retirement age and lifetime exposure to occupational physical workload (standing/walking ≥4 h/day; lifting ≥25 kg; energetic work sufficient to induce sweating and manual work). RESULTS: Complete data on occupational exposures were available for 860 adults (488 men and 372 women) who had worked ≥20 years. Their mean age was 65 years, and many reported heavy physical workplace activities over prolonged durations. There were no statistically significant associations between total hip BMD and any of these measures of lifetime occupational physical activity in men or women. CONCLUSIONS: Lifetime cumulative occupational activity was not associated with hip BMD at retirement age. Our findings suggest that, if sedentary work conveys an increased risk of hip fracture, it is unlikely that the mechanism is through reductions in BMD at the hip and may relate to other physical effects, such as falls risk. Further studies will be needed to test this hypothesis.

Dietary total antioxidant capacity is related to glucose tolerance in older people: the Hertfordshire Cohort Study.

BACKGROUND AND AIMS: Dietary antioxidants may play a protective role in the aetiology of type 2 diabetes. However, observational studies that examine the relationship between the antioxidant capacity of the diet and glucose metabolism are limited, particularly in older people. We aimed to examine the relationships between dietary total antioxidant capacity (TAC) and markers of glucose metabolism among 1441 men and 1253 women aged 59-73 years who participated in the Hertfordshire Cohort Study, UK. METHODS AND RESULTS: Diet was assessed by food frequency questionnaire. Dietary TAC was estimated using published databases of TAC measured by four different assays: oxygen radical absorbance capacity (ORAC), ferric-reducing ability of plasma (FRAP), total radical-trapping antioxidant parameter (TRAP) and trolox equivalent antioxidant capacity (TEAC). Fasting and 120-min plasma glucose and insulin concentrations were measured during a standard 75-g oral glucose tolerance test. In men, dietary TAC estimated by all four assays was inversely associated with fasting insulin concentration and homoeostasis model assessment of insulin resistance (HOMA-IR); with the exception of ORAC, dietary TAC was also inversely related to 120-min glucose concentration. There were no associations with fasting glucose or 120-min insulin concentrations. In women, with the exception of the association between ORAC and 120-min insulin concentration, dietary TAC estimated by all assays showed consistent inverse associations with fasting and 120-min glucose and insulin concentrations and HOMA-IR. These associations were more marked among women with BMI ≥ 30 kg/m(2). CONCLUSION: These findings suggest dietary TAC may have important protective effects on glucose tolerance, especially in older obese women.

Selective reduction in trabecular volumetric bone mineral density during treatment for childhood acute lymphoblastic leukemia.

During treatment of childhood acute lymphoblastic leukemia (ALL) fracture incidence is increased. Studies using DXA, which measures a composite of both trabecular and cortical BMD, have shown reduced BMD during treatment. We investigated changes in compartmental (cortical and trabecular) volumetric BMD (vBMD) and bone geometry using peripheral quantitative computed tomography. These outcomes were also analysed in relation to adiposity and treatment factors. Thirty nine patients with ALL (64% male, median age 7.2 years (4.1-16.9)) were compared to 34 healthy controls (50% male, median age 9.1 years (4.4-18.7)). DXA-derived age-specific standard deviation scores (SDS) of the lumbar spine (LS) and femoral neck (FN) were reduced in subjects with ALL compared to controls (p ≤ 0.01). This persisted following adjustment for body size using height-specific SDS (LS -0.72 ± 1.02 vs -0.18 ± 0.72, p=0.01; FN -1.53 ± 0.96 vs -0.74 ± 0.74, p=0.001) and bone mineral apparent density (BMAD) SDS (LS -0.76 ± 1.14 vs 0.04 ± 1.08, p=0.01; FN -1.63 ± 1.38 vs -0.16 ± 1.20, p<0.001). Radial and tibial trabecular vBMD was also reduced (196.5 ± 54.9 mg/cm(3) vs 215.2 ± 39.9 mg/cm(3), p=0.03 and 232.8 ± 60.3mg/cm(3) vs 267.5 ± 60.2mg/cm(3), p=0.002, respectively), but cortical vBMD at the radius and tibia was similar in patients and controls. A lowered tibial bone strength index (BSI) was identified in patients with ALL (53.9 ± 23.1mg/mm(4) vs 82.5 ± 27.8 mg/mm(4), p<0.001) suggesting lower fracture threshold from compressive forces. No relationships with measures of adiposity, duration of treatment or cumulative corticosteroid dose were identified. Our findings therefore suggest that reduction in trabecular vBMD during childhood ALL treatment may contribute to the observed increased fracture incidence and bony morbidity in this group.

The relationship of dietary patterns with adult lung function and COPD.

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns. The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis. Using regression analysis, after controlling for confounders, a "prudent" pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with forced expiratory volume in 1 s (FEV(1)) (trend p-value <0.001 in males, 0.008 in females) (difference in FEV(1) between top and bottom quintiles of pattern score, 0.18 L (95% CI 0.08-0.28 L) in males, 0.08 L (95% CI 0.00-0.16 L) in females). This pattern was also positively associated with forced vital capacity (FVC) in both sexes. Males with a higher "prudent" pattern score had a higher FEV(1)/FVC (trend p-value 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile 0.46, 95% CI 0.26-0.81; trend p-value 0.012). Associations in males were stronger in smokers than nonsmokers (interaction p-value for FEV(1)/FVC 0.002). A "prudent" dietary pattern may protect against impaired lung function and COPD, especially in male smokers.

Maternal predictors of neonatal bone size and geometry: the Southampton Women's Survey.

Early growth is associated with later risk of osteoporosis and fractures. In this study, we aimed to evaluate the relationships between maternal lifestyle and body composition and neonatal bone size, geometry and density in the offspring. Participants were recruited from the Southampton Women's Survey, a unique prospective cohort of 12,500 initially non-pregnant women aged 20-34 years, resident in Southampton, UK. These women were studied in detail before and during pregnancy, and the offspring underwent anthropometric and bone mineral assessment (using dual energy-X-ray absorptiometry) at birth. A total of 841 mother-baby pairs were studied (443 boys and 398 girls). The independent predictors of greater neonatal whole body bone area (BA) and bone mineral content included greater maternal birthweight, height, parity, triceps skinfold thickness and lower walking speed in late pregnancy. Maternal smoking was independently associated with lower neonatal bone mass. Neonatal BA adjusted for birth length (a measure of bone width) was predicted positively by maternal parity and late pregnancy triceps skinfold thickness and negatively by late pregnancy walking speed. These findings were similar in both genders. We have confirmed, in a large cohort, previous findings that maternal lifestyle and body build predict neonatal bone mineral; additionally, maternal parity and fat stores and walking speed in late pregnancy were associated with neonatal bone geometry. These findings may suggest novel public health strategies to reduce the burden of osteoporotic fracture in future generations.

Early development and osteoporosis and bone health.

Osteoporosis is a skeletal disorder characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) and hypothalamo-pituitary-adrenal (HPA) axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have shown that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Childhood growth rates have been directly linked to the risk of hip fracture many decades later, and now evidence is emerging from experimental animal studies that support these observational data. Recent studies have also highlighted epigenetic phenomena as potential mechanisms underlying the findings from epidemiological studies.

Cigarette smoking, birthweight and osteoporosis in adulthood: results from the hertfordshire cohort study.

We looked for interaction between early environment and adult lifestyle in determination of bone mineral content (BMC) and bone mineral density (BMD) among 498 men and 468 women for whom birth records were available. Participants completed a health questionnaire, and bone densitometry (DXA) of the lumbar spine and femoral neck performed.We found no relationships between cigarette and alcohol consumption, physical activity and either BMC or BMD after adjustment for age, body mass index, dietary calcium, social class, HRT use and years since menopause. However, male current smokers in the lowest third of birth weight had lower femoral neck BMD than ex- or never smokers from the lowest birth weight third (p value for interaction term = 0.04). Similar trends were seen with femoral neck BMC and lumber spine BMC.Individuals of lower birth weight may be particularly vulnerable to the effects of bone noxious stimuli such as cigarette smoking.

Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort Study.

INTRODUCTION: Sarcopenia, the loss of muscle mass and strength with age, is significantly associated with type 2 diabetes in older people. AIM: To determine whether there is a relationship between grip strength and features of the metabolic syndrome. DESIGN: Cross-sectional study. METHODS: Data were collected on grip strength, fasting glucose, triglycerides and HDL cholesterol, blood pressure, waist circumference and 2 h glucose after an oral glucose tolerance test, in a population-based sample of 2677 men and women aged 59-73 years. RESULTS: In men and women combined, a standard deviation (SD) decrease in grip strength was significantly associated with higher: fasting triglycerides (0.05 SD unit increase, 95%CI 0.02-0.09, p = 0.006); blood pressure (OR 1.13, 95%CI 1.04-1.24, p = 0.004); waist circumference (0.08 SD unit increase, 95%CI 0.06-0.10, p < 0.001); 2 h glucose (0.07 SD unit increase, 95%CI 0.03-0.11, p = 0.001) and HOMA resistance (0.05 SD unit increase, 95%CI 0.01-0.09, p = 0.008), after adjustment for gender, weight, age, walking speed, social class, smoking habit and alcohol intake. Lower grip strength was also significantly associated with increased odds of having the metabolic syndrome according to both the ATPIII (OR 1.18, 95%CI 1.07-1.30, p < 0.001) and IDF definitions (OR 1.11, 95%CI 1.01-1.22, p = 0.03). DISCUSSION: Our findings suggest that impaired grip strength is associated with the individual features, as well as with the overall summary definitions, of the metabolic syndrome. The potential for grip strength to be used in the clinical setting needs to be explored.

Placental calcium transporter (PMCA3) gene expression predicts intrauterine bone mineral accrual.

Evidence is accruing that environmental exposures during critical periods of early development induce persisting changes in skeletal growth, and alter fracture risk in later life. We have previously demonstrated that placental calcium transport, partly determined by maternal 25-(OH) vitamin D status, may underlie this phenomenon. However, the precise relationship between expression of calcium transport proteins in the human placenta, and neonatal bone mineral accrual in the offspring, remains unknown. Tissue samples from 70 human placentae were fast frozen in liquid nitrogen and stored at -70 degrees C. A quantitative real time reverse transcriptase polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1-4, using beta-actin as a control gene. Neonatal whole body bone area, mineral content and areal density (BA, BMC, BMD) were measured within 2 weeks of birth using DXA. PMCA3 mRNA expression predicted BA (r=0.28, p=0.02), BMC (r=0.25, p=0.04), placental weight (r=0.26, p=0.04) and birth weight (r=0.33, p=0.006) of the neonate. In a multivariate model, the relationship between placental PMCA3 expression and neonatal BMC was independent of maternal height, pre-pregnant fat stores, parity, physical activity, smoking, and calcium intake (p<0.05). Expression of the placental calcium transporter PMCA3 mRNA predicts neonatal whole body bone mineral content. This association may explain, in part, the mechanism whereby a mother's 25(OH)-vitamin D stores influence her offspring's bone mass.

Parental determinants of neonatal body composition.

BACKGROUND: The prevalence of both childhood and adult obesity is rising in the developed world, and there is increasing interest in its underlying causes. A number of studies suggest a positive relationship between birth weight and childhood body mass index, but less is known about specific prenatal environmental influences on more direct measures of obesity. We used data from the Southampton Women's Survey to investigate parental influences on neonatal body composition ascertained by dual x-ray absorptiometry. METHODS: Participating mothers were characterized in detail (anthropometry, lifestyle, diet) before and during pregnancy; information was also obtained on their partners. The offspring underwent assessment of fat and lean body mass by dual x-ray absorptiometry within 2 wk of birth. Linear regression methods were used to explore the parental determinants of neonatal body composition. RESULTS: Complete data were available for 448 mother-offspring pairs. Taller women and those with higher parity had offspring with increased birth weight, fat, and lean mass (P < 0.05). Mothers who were taller, of greater parity, had greater fat stores, or walked more slowly also had offspring with greater proportionate body fat at birth (all P < 0.05). There was a weaker trend toward lower percentage fat and greater percentage lean in the offspring of mothers who smoked during pregnancy. CONCLUSION: Maternal size, parity, smoking history, walking speed, and fat stores are independent determinants of neonatal body composition. If these influences are shown to have persisting effects on body composition through to adulthood, they point to novel public health interventions early in life to prevent later obesity.

Urinary CTX-II and glucosyl-galactosyl-pyridinoline are associated with the presence and severity of radiographic knee osteoarthritis in men.

OBJECTIVE: To investigate the association between biochemical markers of bone, cartilage, and synovial turnover with the presence and severity of knee osteoarthritis (OA) in men. METHODS: 176 men aged 59-70 years from the MRC Hertfordshire Cohort were studied. Weightbearing anteroposterior and lateral semiflexed radiographs were taken of both knees. A lifestyle questionnaire including basic demographic details and a questionnaire detailing knee pain was completed. This random sample was stratified based on the Kellgren and Lawrence (K&L) score, and the following biochemical markers were analysed: serum osteocalcin, serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), urinary C-terminal crosslinked telopeptide of type II collagen (CTX-II), and urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-Pyd). RESULTS: Age, body mass index (BMI), social class, smoking, and alcohol consumption were similar across K&L grades. Only one subject had a grade 4 K&L score, and was amalgamated with grade 3 subjects. A strong significant association was found between the presence of knee OA and urinary CTX-II and urinary Glc-Gal-Pyd (p=0.0001 and p=0.009), which persisted after adjustment for age and BMI. A significant positive association was also found between urinary CTX-II and urinary Glc-Gal-Pyd and the severity of K&L grade, joint space narrowing, and osteophytes scores, which persisted after adjustment for age and BMI. No associations between the presence and severity of knee OA were found for serum CTX-I or serum osteocalcin. CONCLUSIONS: Urinary CTX-II and Glc-Gal-Pyd, but not systemic markers of bone turnover, are strongly associated with disease severity and the presence of OA at the tibiofemoral and patellofemoral joints in men.