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.

Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Surgical outcomes of total duct excision in the diagnosis and management of nipple discharge.

INTRODUCTION: Total duct excision (TDE) is performed for the diagnosis and management of nipple discharge. The Association of Breast Surgery's recent guidelines recommend considering diagnostic surgery for single-duct, blood-stained or clear nipple discharge, and for symptomatic management. METHODS: We retrospectively reviewed the diagnostic and surgical outcomes of all cases of TDE between January 2013 and November 2019. RESULTS: In total, 259 TDEs were carried out: 219 for nipple discharge, 29 for recurrent mastitis, 3 for screening abnormalities and 8 for breast lumps. Of the nipple discharge group, 121 had blood-stained discharge. Mean patient age was 52 years (range 19-81). Median follow-up time was 45 months (interquartile range 24-63). The following cases were identified on histopathology: 236 benign breast changes, 10 atypical ductal hyperplasia, 4 lobular carcinoma in situ, 2 low-grade ductal carcinoma in situ (DCIS), 3 intermediate-grade DCIS, 2 high-grade DCIS and 2 invasive ductal carcinomas. In total, 3.5% of patients who underwent TDE had a diagnosis of DCIS or invasive carcinoma. Blood-stained discharge was associated with a significant increase in risk of DCIS or carcinoma compared with other nipple discharge colours (p = 0.043). The most common complications of TDE were infection, poor wound healing and haematoma. Nipple discharge recurred in 14.2% of cases. CONCLUSIONS: TDE can be considered for the diagnostics and management of nipple discharge. Blood-stained nipple discharge increases the risk of DCIS or malignancy, but the majority of the time TDE reveals benign breast pathology.

Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. INTRODUCTION: The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. METHODS: The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. RESULTS AND CONCLUSION: The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study): a superiority randomised clinical trial to evaluate the effectiveness and cost-effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) syndrome is a symptom complex affecting 12-14% of the UK adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. OAB has a negative impact on women's social, physical, and psychological wellbeing. Initial treatment includes lifestyle modifications, bladder retraining, pelvic floor exercises and pharmacological therapy. However, these measures are unsuccessful in 25-40% of women (refractory OAB). Before considering invasive treatments, such as Botulinum toxin injection or sacral neuromodulation, most guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity (DO). However, urodynamics may fail to show evidence of DO in up to 45% of cases, hence the need to evaluate its effectiveness and cost-effectiveness. FUTURE (Female Urgency, Trial of Urodynamics as Routine Evaluation) aims to test the hypothesis that, in women with refractory OAB, urodynamics and comprehensive clinical assessment is associated with superior patient-reported outcomes following treatment and is more cost-effective, compared to comprehensive clinical assessment only. METHODS: FUTURE is a pragmatic, multi-centre, superiority randomised controlled trial. Women aged ≥ 18 years with refractory OAB or urgency predominant mixed urinary incontinence, and who have failed/not tolerated conservative and medical treatment, are considered for trial entry. We aim to recruit 1096 women from approximately 60 secondary/tertiary care hospitals across the UK. All consenting women will complete questionnaires at baseline, 3 months, 6 months and 15 months post-randomisation. The primary outcome is participant-reported success at 15 months post-randomisation measured using the Patient Global Impression of Improvement. The primary economic outcome is incremental cost per quality-adjusted life year gained at 15 months. The secondary outcomes include adverse events, impact on other urinary symptoms and health-related quality of life. Qualitative interviews with participants and clinicians and a health economic evaluation will also be conducted. The statistical analysis of the primary outcome will be by intention-to-treat. Results will be presented as estimates and 95% CIs. DISCUSSION: The FUTURE study will inform patients, clinicians and policy makers whether routine urodynamics improves treatment outcomes in women with refractory OAB and whether it is cost-effective. TRIAL REGISTRATION: ISRCTN63268739 . Registered on 14 September 2017.

How do we improve adolescent diet and physical activity in India and sub-Saharan Africa? Findings from the Transforming Adolescent Lives through Nutrition (TALENT) consortium.

OBJECTIVE: Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups. SETTING: Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries. DESIGN: Focus groups with adolescents and caregivers carried out by trained researchers. RESULTS: Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to 'belong' in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time. CONCLUSIONS: Interventions to improve adolescents' diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.

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.

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.

Management of mesh complications following surgery for stress urinary incontinence or pelvic organ prolapse: a systematic review.

BACKGROUND: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications. OBJECTIVE: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'. SEARCH STRATEGY: Search strategies were developed for each indication for referral. SELECTION CRITERIA: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen. DATA COLLECTION AND ANALYSIS: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. MAIN RESULTS: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. CONCLUSIONS: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future. TWEETABLE ABSTRACT: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.

Cancer survivor perspectives on sharing patient-generated health data with central cancer registries.

PURPOSE: Central cancer registries collect data and provide population-level statistics that can be tracked over time; yet registries may not capture the full range of clinically relevant outcomes. Patient-generated health data (PGHD) include health/treatment history, biometrics, and patient-reported outcomes (PROs). Collection of PGHD would broaden registry outcomes to better inform research, policy, and care. However, this is dependent on the willingness of patients to share such data. This study examines cancer survivors' perspectives about sharing PGHD with central cancer registries. METHODS: Three U.S. central registries sampled colorectal, non-Hodgkin lymphoma, and metastatic breast cancer survivors 1-4 years after diagnosis, recruiting them via mail to participate in one of seven focus groups (n = 52). Group discussions were recorded, transcribed, and thematically analyzed. RESULTS: Most survivor-participants were unaware of the existence of registries. After having registries explained, all participants expressed their willingness to share PGHD with them if treated confidentially. Participants were willing to provide information on a variety of topics (e.g., medical history, medications, symptoms, financial difficulties, quality of life, biometrics, nutrition, exercise, and mental health), with a focus on long-term effects of cancer and its treatment. Participants' preferred mode for providing data varied. Participants were also interested in receiving information from registries. CONCLUSIONS: Our results suggest that registry-based collection of PGHD is acceptable to most cancer survivors and could facilitate registry-based efforts to collect PGHD/PROs. Central cancer registry-based collection of PGHD/PROs, especially on long-term effects, could enhance registry support of cancer control efforts including research and population health management.

Adverse effects of topical photodynamic therapy: a consensus review and approach to management.

BACKGROUND: Topical photodynamic therapy (PDT) is widely used to treat superficial nonmelanoma skin cancer and dysplasia, and is generally well tolerated. However, as with all treatments, adverse effects may occur and awareness may facilitate approaches to prevention and management. OBJECTIVES: To review the available evidence relating to the adverse effects of topical PDT, to help inform recommendations in updated clinical guidelines produced by the British Association of Dermatologists and British Photodermatology Group, and the efficacy of preventative and therapeutic approaches. METHODS: This review summarizes the published evidence related to the adverse effects of topical PDT and attempts to interpret this evidence in the context of patient risk and management. RESULTS: Pain and discomfort during PDT are acute adverse effects, which can be minimized through the use of modified and low-irradiance PDT regimens and do not therefore usually limit successful treatment delivery. Other adverse effects include the risk of contact allergy to photosensitizer prodrugs, although this is rare but should be kept in mind, particularly for patients who have received multiple PDT treatments to larger areas. There are no other significant documented longer-term risks and, to date, no evidence of cumulative toxicity or photocarcinogenic risk. CONCLUSIONS: Topical PDT is usually well tolerated, reinforcing the utility of this important therapeutic option in dermatology practice. The main acute adverse effect of pain can typically be minimized through preventative approaches of modified PDT regimens. Other adverse effects are uncommon and generally do not limit treatment delivery.

Breech presentation is associated with lower bone mass and area: findings from the Southampton Women's Survey.

We compared bone outcomes in children with breech and cephalic presentation at delivery. Neonatal whole-body bone mineral content (BMC) and area were lower in children with breech presentation. At 4 years, no differences in whole-body or spine measures were found, but hip BMC and area were lower after breech presentation. INTRODUCTION: Breech presentation is associated with altered joint shape and hip dysplasias, but effects on bone mineral content (BMC), area (BA) and density (BMD) are unknown. METHODS: In the prospective Southampton Women's Survey mother-offspring cohort, whole-body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) in 1430 offspring, as neonates (mean age 6 days, n = 965, 39 with a breech presentation at birth) and/or at age 4.1 years (n = 999, 39 breech). Hip and spine bone outcomes were also measured at age 4 years. RESULTS: Neonates with breech presentation had 4.2 g lower whole-body BMC (95% CI -7.4 to - 0.9 g, P = 0.012) and 5.9 cm2 lower BA (- 10.8 to - 1.0 cm2, P = 0.019), but BMD was similar between groups (mean difference - 0.007, - 0.016 to 0.002 g/cm2, P = 0.146) adjusting for sex, maternal smoking, gestational diabetes, mode of delivery, social class, parity, ethnicity, age at scan, birthweight, gestational age and crown-heel length. There were no associations between breech presentation and whole-body outcomes at age 4 years, but, in similarly adjusted models, regional DXA (not available in infants) showed that breech presentation was associated with lower hip BMC (- 0.51, - 0.98 to - 0.04 g, P = 0.034) and BA (- 0.67, - 1.28 to - 0.07 cm2, P = 0.03) but not with BMD (- 0.009, - 0.029 to 0.012 g, P = 0.408), or spine outcomes. CONCLUSIONS: These results suggest that breech presentation is associated with lower neonatal whole-body BMC and BA, which may relate to altered prenatal loading in babies occupying a breech position; these differences did not persist into later childhood. Modest differences in 4-year hip BMC and BA require further investigation.

Conventional and combination topical photodynamic therapy for basal cell carcinoma: systematic review and meta-analysis.

BACKGROUND: Topical photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC). OBJECTIVES: To compare efficacy, cosmesis and tolerability of PDT for BCC with alternative treatments. METHODS: MEDLINE, PubMed, Embase and CENTRAL databases were searched from inception until 1 September 2017. Included studies were randomized controlled trials (RCTs) of PDT for nodular (n) and superficial (s) BCC reporting at least one of the following outcomes: clearance at 3 months and sustained at 1 or 5 years; recurrence at ≥ 1 year; cosmesis; adverse events; tolerability. RESULTS: From 2331 search results, 15 RCTs (2327 patients; 3509 BCCs) were included. PDT efficacy (5-year sustained clearance) was high but inferior to excisional surgery [nBCC pooled risk ratio (RR) 0·76; 95% confidence interval (CI) 0·63-0·91], and without re-treatment of partially responding lesions, was modestly inferior to imiquimod (sBCC: RR 0·81; 95% CI 0·70-0·95) and similar to fluorouracil (sBCC: RR 0·88; 95% CI 0·75-1·04). Five-year sustained clearance was inferior with conventional vs. fractionated PDT (sBCC: RR 0·76; 95% CI 0·68-0·84). PDT cosmesis was superior to surgery (sBCC: RR 1·68, 95% CI 1·32-2·14; nBCC: RR 1·82, 95% CI 1·19-2·80) and cryosurgery (BCC: RR 3·73, 95% CI 1·96-7·07), and without re-treatment of partially responding lesions was similar to imiquimod (sBCC: RR 1·01, 95% CI 0·85-1·19) and fluorouracil (sBCC: RR 1·04, 95% CI 0·88-1·24). Peak pain was higher but of shorter duration with PDT than topical treatments. Serious adverse reactions were rarer with PDT than imiquimod (sBCC: RR 0·05, 95% CI 0·00-0·84) and fluorouracil (sBCC: RR 0·11, 95% CI 0·01-2·04). Combination PDT regimens demonstrated reduced recurrence and improved cosmesis; however, results from these small studies were often nonsignificant. CONCLUSIONS: PDT is an effective treatment for low-risk BCC, with excellent cosmesis and safety. Imiquimod has higher efficacy than single-cycle PDT but more adverse effects. Highest efficacy is with excisional surgery. Fractionated and combination PDT options warrant further study.

P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a mouse model of intrauterine inflammation.

The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1ß secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we utilized embryo transfer experiments to delineate whether the P2X7 was the key mediator of IU inflammation-associated brain injury on maternal or fetal sides. In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth rate, improved offspring performance on neuromotor tests as well as the dendritic arborization and density of cortical neurons. Embryo transfer experiments demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects on offspring. Both genetic and pharmacologic blockade of IL-1ß signaling, by targeting maternal P2X7R, ameliorated perinatal brain injury following exposure to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically useful tool to prevent both preterm birth and prematurity-associated perinatal brain injury, and further studies are urgently needed.

Hispanic mothers' beliefs regarding HPV vaccine series completion in their adolescent daughters.

Rates of human papillomavirus (HPV) vaccine series completion among adolescent Hispanic females in Texas in 2014 (∼39%) lag behind the Healthy People 2020 goal (80%). This qualitative study identifies Hispanic mothers' salient behavioral, normative and control beliefs regarding having their adolescent daughters complete the vaccine series. Thirty-two mothers of girls (aged 11-17) that had received at least one dose of the HPV vaccine, completed in-depth interviews. Six girls had received one dose of the HPV vaccine, 10 girls had received two doses, and 16 girls had received all three doses. The questions elicited salient: (i) experiential and instrumental attitudes (behavioral beliefs); (ii) supporters and non-supporters (normative beliefs) and (iii) facilitators and barriers (control beliefs). Directed content analysis was employed to select the most salient beliefs. Mothers: (i) expressed salient positive feelings (e.g. good, secure, happy and satisfied); (ii) believed that completing the series resulted in positive effects (e.g. protection, prevention); (iii) believed that the main supporters were themselves, their daughter's father and doctor with some of their friends not supporting series completion and (iv) believed that vaccine affordability, information, transportation, ease of scheduling and keeping vaccination appointments and taking their daughter's immunization card to appointments were facilitators. This study represents the first step in building theory-based framework of vaccine series completion for this population. The beliefs identified provide guidance for health care providers and intervention developers.

Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (ß-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Bone mineral content and areal density, but not bone area, predict an incident fracture risk: a comparative study in a UK prospective cohort.

We studied a prospective UK cohort of women aged 20 to 80 years, assessed by dual-energy X-ray absorptiometry (DXA) at baseline. Bone mineral content (BMC) and areal bone mineral density (aBMD), but not bone area (BA), at femoral neck, lumbar spine and the whole body sites were similarly predictive of incident fractures. BACKGROUND: Low aBMD, measured by DXA, is a well-established risk factor for future fracture, but little is known about the performance characteristics of other DXA measures such as BA and BMC in fracture prediction. We therefore investigated the predictive value of BA, BMC and aBMD for incident fracture in a prospective cohort of UK women. METHODS: In this study, 674 women aged 20-80 years, recruited from four GP practices in Southampton, underwent DXA assessment (proximal femur, lumbar spine, total body) between 1991 and 1993. All women were contacted in 1998-1999 with a validated postal questionnaire to collect information on incident fractures and potential confounding factors including medication use. Four hundred forty-three women responded, and all fractures were confirmed by the assessment of images and radiology reports by a research nurse. Cox proportional hazard models were used to explore the risk of incident fracture, and the results are expressed as hazard ratio (HR) per 1 SD decrease in the predictor and 95% CI. Associations were adjusted for age, BMI, alcohol consumption, smoking, HRT, medications and history of fracture. RESULTS: Fifty-five women (12%) reported a fracture. In fully adjusted models, femoral neck BMC and aBMD were similarly predictive of incident fracture. Femoral neck BMC: HR/SD = 1.64 (95%CI: 1.19, 2.26; p = 0.002); femoral neck aBMD: HR/SD = 1.76 (95%CI: 1.19, 2.60; p = 0.005). In contrast, femoral neck BA was not associated with incident fracture, HR/SD = 1.15 (95%CI: 0.88, 1.50; p = 0.32). Similar results were found with bone indices at the lumbar spine and the whole body. CONCLUSIONS: In conclusion, BMC and aBMD appear to predict incident fracture with similar HR/SD, even after adjustment for body size. In contrast, BA only weakly predicted the future fracture. These findings support the use of DXA aBMD in fracture risk assessment, but also suggest that factors which specifically influence BMC will have a relevance to the risk of the incident fracture.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower ß C-terminal cross-linked telopeptide (ß-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and ß-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and ß-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

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.