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Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.

OBJECTIVES: To evaluate the use of a short questionnaire to assess diet quality in older adults.DESIGN: Cross-sectional study.SETTING: Hertfordshire, UK PARTICIPANTS: 3217 community-dwelling older adults (59-73 years)MEASUREMENTS: Diet was assessed using an administered food frequency questionnaire (FFQ); two measures of diet quality were defined by calculating participants’ ‘prudent diet’ scores, firstly from a principal component analysis of the data from the full FFQ (129 items) and, secondly, from a short version of the FFQ (including 24 indicator foods). Scores calculated from the full and short FFQ were compared with nutrient intake and blood concentrations of vitamin C and lipids.RESULTS: Prudent diet scores calculated from the full FFQ and short FFQ were highly correlated (0.912 in men, 0.904 in women). The pattern of associations between nutrient intake (full FFQ) and diet scores calculated using the short and full FFQs were very similar, both for men and women. Prudent diet scores calculated from the full and short FFQs also showed comparable patterns of association with blood measurements: in men and women, both scores were positively associated with plasma vitamin C concentration and serum HDL; in women, an inverse association with serum triglycerides was also observed. CONCLUSIONS: A short food-based questionnaire provides useful information about the diet quality of older adults. This simple tool does not require nutrient analysis, and has the potential to be of value to non-specialist researchers.

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. 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). 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. 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

Objectives - A national audit was performed assessing the early management of suspected inflammatory arthritis by English and Welsh rheumatology units. The aim of this audit was to measure the performance of rheumatology services against National Institute for Health and Care Excellence (NICE) quality standards (QSs) for the management of early inflammatory arthritis benchmarked to regional and national comparators for the first time in the UK.Methods - All individuals >16 years of age presenting to rheumatology services in England and Wales with suspected new-onset inflammatory arthritis were included in the audit. Information was collected against six NICE QSs that pertain to early inflammatory arthritis management.Results - We present national data for the 6354 patients recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health boards in England and Wales participated in this audit. Only 17% of patients were referred by their general practitioner within 3 days of first presentation. Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of patients. The target of DMARD initiation within 6 weeks of referral was achieved in 53% of RA patients; 36% were treated with combination DMARDs and 82% with steroids within the first 3 months of specialist care. Fifty-nine per cent of patients received structured education on their arthritis within 1 month of diagnosis. In total, 91% of patients had a treatment target set; the agreed target was achieved within 3 months of specialist review in only 27% of patients. Access to urgent advice via a telephone helpline was reported to be available in 96% of trusts.Conclusion - The audit has highlighted gaps between NICE standards and delivery of care, as well as substantial geographic variability.

BACKGROUND: Substance P (SP) is a pain- and inflammation-related neuropeptide which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1 receptors have been implicated in joint pain, inflammation and damage in animal models and human studies of osteoarthritis (OA). The aim of this study was to test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated with pain in individuals with radiographic knee OA.METHODS: Participants from the Genetics of OA and Lifestyle study were used for the discovery group (n = 1615). Genotype data for six SNPs selected to cover most variation in the TACR1 gene were used to test for an association with symptomatic OA. Replication analysis was performed using data from the Chingford 1000 Women Study, Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater OA Study. In total, n = 1715 symptomatic OA and n = 735 asymptomatic OA individuals were analysed.RESULTS: Out of six SNPs tested in the TACR1 gene, one (rs11688000) showed a nominally significant association with a decreased risk of symptomatic OA in the discovery cohort. This was then replicated in four additional cohorts. After adjusting for age, gender, body mass index and radiographic severity, the G (minor) allele at rs11688000 was associated with a decreased risk of symptomatic OA compared to asymptomatic OA cases (p = 9.90 × 10(-4) , OR = 0.79 95% 0.68-0.90 after meta-analysis).CONCLUSIONS: This study supports a contribution from the TACR1 gene in human OA pain, supporting further investigation of this gene's function in OA.SIGNIFICANCE: This study contributes to the knowledge of the genetics of painful osteoarthritis, a condition which affects millions of individuals worldwide. Specifically, a contribution from the TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.

Objectives - Our aim was to conduct a national audit assessing the impact and experience of early management of inflammatory arthritis by English and Welsh rheumatology units. The audit enables rheumatology services to measure for the first time their performance, patient outcomes and experience, benchmarked to regional and national comparators.Methods - All individuals >16 years of age presenting to English and Welsh rheumatology services with suspected new-onset inflammatory arthritis were included in the audit. Clinician- and patient-derived outcome and patient-reported experience measures were collected.Results - Data are presented for the 6354 patients recruited from 1 February 2014 to 31 January 2015. Ninety-seven per cent of English and Welsh trusts participated. At the first specialist assessment, the 28-joint DAS (DAS28) was calculated for 2659 (91%) RA patients [mean DAS28 was 5.0 and mean Rheumatoid Arthritis Impact of Disease (RAID) score was 5.6]. After 3 months of specialist care, the mean DAS28 was 3.5 and slightly >60% achieved a meaningful DAS28 reduction. The average RAID score and reduction in RAID score were 3.6 and 2.4, respectively. Of the working patients ages 16–65 years providing data, 7, 5, 16 and 37% reported that they were unable to work, needed frequent time off work, occasionally and rarely needed time off work due to their arthritis, respectively; only 42% reported being asked about their work. Seventy-eight per cent of RA patients providing data agreed with the statement ‘Overall in the last 3 months I have had a good experience of care for my arthritis’; Conclusion - This audit demonstrates that most RA patients have severe disease at the time of presentation to rheumatology services and that a significant number continue to have high disease activity after 3 months of specialist care. There is a clear need for the National Health Service to develop better systems for capturing, coding and integrating information from outpatient clinics, including measures of patient experience and outcome and measures of ability to work.

This is a post-peer-review, pre-copyedit version of an article published in Archives of Osteoporosis. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11657-017-0348-x. Summary The influence of birth weight and length on bone mineral parameters in adolescence is unclear. We found a positive association between birth size and bone mineral content, attenuated by lifestyle factors. This highlights the impact of environmental stimuli and lifestyle during growth. Purpose The influence of birth weight and length on bone mineral density and content later in life is unclear, especially in adolescence. This study evaluated the impact of birth weight and length on bone mineral density and content among adolescents. Methods We included 961 participants from the population-based Fit Futures study (2010–2011). Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) and bone mineral content (BMC) at femoral neck (FN), total hip (TH) and total body (TB). BMD and BMC measures were linked with birth weight and length ascertained from the Medical Birth Registry of Norway. Linear regression models were used to investigate the influence of birth parameters on BMD and BMC. Results Birth weight was positively associated with BMD-TB and BMC at all sites among girls; standardized β coefficients [95% CI] were 0.11 [0.01, 0.20] for BMD-TB and 0.15 [0.06, 0.24], 0.18 [0.09, 0.28] and 0.29 [0.20, 0.38] for BMC-FN, TH and TB, respectively. In boys, birth weight was positively associated with BMC at all sites with estimates of 0.10 [0.01, 0.19], 0.12 [0.03, 0.21] and 0.15 [0.07, 0.24] for FN, TH and TB, respectively. Corresponding analyses using birth length as exposure gave significantly positive associations with BMC at all sites in both sexes. The significant positive association between birth weight and BMC-TB in girls, and birth length and BMC-TB in boys remained after multivariable adjustment. Conclusions We found a positive association between birth size and BMC in adolescence. However, this association was attenuated after adjustment for weight, height and physical activity during adolescence.

Objectives To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. Methods The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). Results This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution and analysis. Conclusions While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA.

It is becoming increasingly apparent that the risk of developing osteoporosis is accrued throughout the entire lifecourse, even from as early as conception. Thus early growth is associated with bone mass at peak and in older age, and risk of hip fracture. Novel findings from mother-offspring cohorts have yielded greater understanding of relationships between patterns of intrauterine and postnatal growth in the context of later bone development. Study of biological samples from these populations has helped characterize potential mechanistic underpinnings, such as epigenetic processes. Global policy has recognized the importance of early growth and nutrition to the risk of developing adult chronic noncommunicable diseases such as osteoporosis; testing of pregnancy interventions aimed at optimizing offspring bone health is now underway. It is hoped that through such programs, novel public health strategies may be established with the ultimate goal of reducing the burden of osteoporotic fracture in older age.

BACKGROUND: poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies. OBJECTIVE: to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries. METHODS: a total of 2,942 men and women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0-12); low PP was defined as a score of ≤9. RESULTS: the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain. CONCLUSION: lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites.

Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10−8) level: 14q24.2 (rs227425, P-value 3.98 × 10−13, SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10−9, CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

Background:Older adults with osteoarthritis (OA) often report that their disease symptoms are exacerbated by weather conditions. This study examines the association between outdoor physical activity (PA) and weather conditions in older adults from 6 European countries and assesses whether outdoor PA and weather conditions are more strongly associated in older persons with OA than in those without the condition.Methods:The American College of Rheumatology classification criteria were used to diagnose OA. Outdoor PA was assessed using the LASA Physical Activity Questionnaire. Data on weather parameters were obtained from weather stations.Results:Of the 2439 participants (65–85 years), 29.6% had OA in knee, hand and/or hip. Participants with OA spent fewer minutes in PA than participants without OA (Median = 42.9, IQR = 20.0 to 83.1 versus Median = 51.4, IQR = 23.6 to 98.6; P < .01). In the full sample, temperature (B = 1.52; P < .001) and relative humidity (B = –0.77; P < .001) were associated with PA. Temperature was more strongly associated with PA in participants without OA (B = 1.98; P < .001) than in those with the condition (B = 0.48; P = .47).Conclusions:Weather conditions are associated with outdoor PA in older adults in the general population. Outdoor PA and weather conditions were more strongly associated in older adults without OA than in their counterparts with OA.

The Hertfordshire Cohort Study is a nationally unique study of men and women born in the English county of Hertfordshire in the early part of the 20th century. Records that detail their health in infancy and childhood have been preserved, their sociodemographic, lifestyle, medical and biological attributes have been characterised in later life, and routinely collected data on their hospital use and mortality have been acquired. This paper provides an overview of the study since its inception in the 1980s, including its methods, findings, and plans for its future.

Sarcopenia is associated with a greater fracture risk. This relationship was originally thought to be explained by an increased risk of falls in sarcopenic individuals. However, in addition, there is growing evidence of a functional muscle-bone unit in which bone health may be directly influenced by muscle function. Because a definition of sarcopenia encompasses muscle size, strength, and physical performance, we investigated relationships for each of these with bone size, bone density, and bone strength to interrogate these hypotheses further in participants from the Hertfordshire Cohort Study. A total of 313 men and 318 women underwent baseline assessment of health and detailed anthropometric measurements. Muscle strength was measured by grip strength, and physical performance was determined by gait speed. Peripheral quantitative computed tomography (pQCT) examination of the calf and forearm was performed to assess muscle cross-sectional area (mCSA) at the 66% level and bone structure (radius 4% and 66% levels; tibia 4% and 38% levels). Muscle size was positively associated with bone size (distal radius total bone area ??=?17.5 mm2/SD [12.0, 22.9]) and strength (strength strain index (??=?23.3 mm3/SD [18.2, 28.4]) amongst women (p?0.001). These associations were also seen in men and were maintained after adjustment for age, height, weight-adjusted-for-height, limb-length-adjusted-for-height, social class, smoking status, alcohol consumption, calcium intake, physical activity, diabetes mellitus, and in women, years since menopause and estrogen replacement therapy. Although grip strength showed similar associations with bone size and strength in both sexes, these were substantially attenuated after similar adjustment. Consistent relationships between gait speed and bone structure were not seen. We conclude that although muscle size and grip strength are associated with bone size and strength, relationships between gait speed and bone structure and strength were not apparent in this cohort, supporting a role for the muscle-bone unit

Introduction: sarcopenia is associated with adverse health outcomes. The aim of this study was to describe the prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus definition.Methods:we applied the EWGSOP definition to 103 community-dwelling men participating in the Hertfordshire Sarcopenia Study (HSS) using both the lowest third of dual-energy X-ray absorptiometry (DXA) lean mass (LM) and the lowest third of skin-fold-based fat-free mass (FFM) as markers of low muscle mass. We also used the FFM approach among 765 male and 1,022 female participants in the Hertfordshire Cohort Study (HCS). Body size, physical performance and self-reported health were compared in participants with and without sarcopenia.Results: the prevalence of sarcopenia in HSS men (mean age 73 years) was 6.8% and 7.8% when using the lowest third of DXA LM and FFM, respectively. DXA LM and FFM were highly correlated (0.91, P < 0.001). The prevalence of sarcopenia among the HCS men and women (mean age 67 years) was 4.6% and 7.9%, respectively. HSS and HCS participants with sarcopenia were shorter, weighed less and had worse physical performance. HCS men and women with sarcopenia had poorer self-reported general health and physical functioning scores.Conclusions: this is one of the first studies to describe the prevalence of sarcopenia in UK community-dwelling older people. The EWGSOP consensus definition was of practical use for sarcopenia case finding. The next step is to use this consensus definition in other ageing cohorts and among older people in a range of health-care settings.

The FRAX(tr) algorithm uses clinical risk factors (CRF) and bone mineral density (BMD) to predict fracture risk but does not include falls history in the calculation. Using results from the Hertfordshire Cohort Study, we examined the relative contributions of CRFs, BMD and falls history to fracture prediction. We studied 2299 participants at a baseline clinic that included completion of a health questionnaire and anthropometric data. A mean of 5.5years later (range 2.9-8.8years) subjects completed a postal questionnaire detailing fall and fracture history. In a subset of 368 men and 407 women, bone densitometry was performed using a Hologic QDR 4500 instrument. There was a significantly increased risk of fracture in men and women with a previous fracture. A one standard deviation drop in femoral neck BMD was associated with a hazards ratio (HR) of incident fracture (adjusted for CRFs) of 1.92 (1.04-3.54) and 1.77 (1.16-2.71) in men and women respectively. A history of any fall since the age of 45years resulted in an unadjusted HR of fracture of 7.31 (3.78-14.14) and 8.56 (4.85-15.13) in men and women respectively. In a ROC curve analysis, the predictive capacity progressively increased as BMD and previous falls were added into an initial model using CRFs alone. Falls history is a further independent risk factor for fracture. Falls risk should be taken into consideration when assessing whether or not to commence medication for osteoporosis and should also alert the physician to the opportunity to target falls risk directly.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease involving the cartilage and many of its surrounding tissues. Disease progression is usually slow but can ultimately lead to joint failure with pain and disability. OA of the hips and knees tends to cause the greatest burden to the population as pain and stiffness in these large weight-bearing joints often leads to significant disability requiring surgical intervention. SOURCES OF DATA: The article reviews the existing data on epidemiology of osteoarthritis and the burden of the disease. AREAS OF AGREEMENT: Symptoms and radiographic changes are poorly correlated in OA. Established risk factors include obesity, local trauma and occupation. The burden of OA is physical, psychological and socioeconomic. AREAS OF CONTROVERSY: Available data does not allow definite conclusion regarding the roles of nutrition, smoking and sarcopenia as risk factors for developing OA. GROWING POINTS: Variable methods of diagnosing osteoarthritis have significantly influenced the comparability of the available literature. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research is required to fully understand how OA affects an individual physically and psychologically, and to determine their healthcare need.

Osteoporotic fracture is associated with considerable morbidity and mortality in women throughout the world. However, significant variation in hip fracture rates among women from different nations has been observed and is likely to represent a combination of real and apparent differences due to ascertainment bias. Higher rates are observed in Caucasian women, with lowest rates observed in black women and intermediate rates among Asian women. These differences are likely to represent a combination of genetic and environmental differences; for example, among European women, the highest fracture rates are observed in Scandinavian women where vitamin D insufficiency is common. In all groups, an increase in absolute fracture numbers is anticipated due to demographic changes.

Summary This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. Introduction We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. Methods Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0–16 g) worn at the waist for 7 days were classified as low (0.5–1.0 g), medium (1.0–1.5 g) or higher (≥1.5 g) impacts. Results There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [−0.02, 0.08]). Conclusions Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA. Electronic supplementary material The online version of this article (doi:10.1007/s00198-016-3810-5) contains supplementary material, which is available to authorized users.

Background Poor diet quality is common among older people, but little is known about influences on food choice, including the role of psychosocial factors at this age. Objective To identify psychosocial correlates of diet quality in a community-dwelling population of men and women aged 59-73 years; to describe relationships with change in diet quality over 10 years. Design Longitudinal cohort, Hertfordshire Cohort Study (HCS). Subjects HCS participants assessed at baseline (1998-2001: 1048 men, 862 women); 183 men and 189 women re-assessed in 2011. Methods Diet was assessed by administered food frequency questionnaire; diet scores were calculated to describe diet quality at baseline and follow-up. A range of psychosocial factors (social support, social network, participation in leisure activities, depression and anxiety, sense of control) were assessed by questionnaire. Results At baseline, better diet quality was related to a range of social factors, including increased confiding/emotional social support (men and women), practical support (men), and a larger social network (women) (all p Conclusions In community-dwelling older adults, a range of social factors, that includes greater participation in leisure activities, were associated with diets of better quality.

Introduction Osteoporosis is a significant public health issue affecting over half of women aged over 50. With an aging population its importance is set to increase further over time. Prevention of fragility fractures avoids significant mortality and morbidity as well as saving significant direct and indirect costs to the economy. In this review, we discuss existing treatments to contextualise the treatment landscape, and demonstrate how our understanding of bone pathophysiology has led to novel therapies – in the form of combinations and altered durations of existing treatments, as well as newer drug therapies. Sources of data Pubmed and Embase were searched for randomised controlled trials of new therapies for osteoporosis. These searches were supplemented with material presented in abstract form at international meetings Areas of agreement New drugs that appear promising in the treatment of osteoporosis include the cathepsin K inhibitor, monoclonal antibodies against sclerostin, and parathyroid hormone related peptide. Areas of controversy Separate to the development of novel drug therapies is the issue of how best to use agents that are currently available to us; specifically which agent to choose, alone or in combination; duration of therapy; how best to identify patients at highest risk of fracture, and to ensure the highest possible adherence to medication. Many of these issues have been addressed in other excellent review papers, and will not be considered in detail here. Growing points As with all new treatments, we await results of long term use, and experience in ‘real life’ patient populations Areas timely for developing research As alluded to above, data are urgently required regarding the optimal duration of therapy; use of combination therapy; ordering of therapies for best therapeutic effect. As stratified medicine becomes more strongly considered in all areas of therapy, its merits in osteoporosis as in other musculoskeletal conditions, is timely and valuable.

Over recent decades, the perception of osteoporosis has changed from that of an inevitable consequence of ageing, to that of a well characterised and treatable chronic non-communicable disease, with major impacts on individuals, healthcare systems and societies. Characterisation of its pathophysiology from the hierarchical structure of bone and the role of its cell population, development of effective strategies for the identification of those most appropriate for treatment, and an increasing armamentarium of efficacious pharmacological therapies, have underpinned this evolution. Despite this marked progress, individuals who experience a fragility fracture remain under-treated in many areas of the world, and there is substantial need for investment both in secondary and primary prevention globally. In this brief article, we give an overview of the pathogenesis of osteoporosis, and summarise current and future approaches to its assessment and ­treatment.

Objective To assess if a coding variant in the gene\ud encoding transient receptor potential cation channel,\ud subfamily V, member 1 ( TRPV1 ) is associated with\ud genetic risk of painful knee osteoarthritis (OA).\ud Methods The Ile585Val TRPV1 variant encoded by\ud rs8065080 was genotyped in 3270 cases of symptomatic\ud knee OA, 1098 cases of asymptomatic knee OA and\ud 3852 controls from seven cohorts from the UK, the USA\ud and Australia. The genetic association between the\ud low-pain genotype Ile–Ile and risk of symptomatic and\ud asymptomatic knee OA was assessed.\ud Results The TRPV1 585 Ile–Ile genotype, reported to\ud be associated with lower thermal pain sensitivity, was\ud associated with a lower risk of symptomatic knee OA\ud in a comparison of symptomatic cases with healthy\ud controls, with an odds ratio (OR) of 0.75 (95% CI 0.64\ud to 0.88; p=0.00039 by meta-analysis) after adjustment\ud for age, sex and body mass index. No difference was\ud seen between asymptomatic OA cases and controls\ud (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile\ud genotype was associated with lower risk of symptomatic\ud versus asymptomatic knee OA adjusting for covariates\ud and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94\ud p=0.0136). TRPV1 expression in articular cartilage was\ud increased by infl ammatory cytokines (tumour necrosis\ud factor α and interleukin 1). However, there were no\ud differences in TRPV1 expression in healthy and arthritic\ud synovial tissue.\ud Conclusions A genotype involved in lower peripheral\ud pain sensitivity is signifi cantly associated with a\ud decreased risk of painful knee OA. This indicates a role for\ud the pro-nociceptive gene TRPV1 in genetic susceptibility\ud to symptomatic knee OA, which may also be infl uenced\ud by a role for this molecule in cartilage function.

Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m(2) greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population.

Papers p 811 The millennium brings with it the 50th anniversary of Hench's discovery that corticosteroids might be used to treat rheumatoid arthritis.1 Attitudes towards such use have waxed and waned since then. Initial hope that steroids might dramatically alter the long term course of the disorder gave way to a recognition of the serious adverse effects that accompany high dose treatment. As a result the use of low dose corticosteroids in arthritis remains highly controversial. Corticosteroids are used widely in medicine today. A recent survey in general practice found that 1.4% of patients aged over 54 were using corticosteroids at a mean dose of 8 mg daily2: rheumatoid arthritis was the indication in 23% of cases. Although rheumatologists claim to use steroids relatively infrequently, audits of patients attending outpatient departments suggest a high prevalence of use (as great as 80%). 3 4 What, then, is the quality of the evidence to support the use of corticosteroids in rheumatoid arthritis? This question is best answered by considering the balance between the risks and benefits of steroid use for short periods (two to three months), with the objective …

Summary: Temporal trends in hip fracture incidence have recently been reported in some developed countries. Such data in Spain has previously been incomplete; this study reports the stratified incidence of hip fractures in people over 65 in Spain during the last 14 years. Introduction: The main objective is to establish whether temporal trends in hip fracture incidence in Spain exist. Methods: Ecological study with data from hospital discharges nationwide. The study includes patients aged ≥65 years during a 14-year period (1997-2010). The analysis compares two periods of four years: 1997-2000 (P1) and 2007-2010 (P2). Results: There were 119,857 fractures in men and 415,421 in women. Comparing periods (P1 vs P2) over 10 years, the crude incidence rate/100,000 inhabitant/year increased an average of 2.3 %/year in men and 1.4 % in women. After adjustment, the rate increased an average of 0.4 %/year in men (p

Osteoporosis constitutes a major public health problem through its association with age-related fractures, most notably those of the proximal femur. Substantial geographic variation has been noted in the incidence of hip fracture throughout the world, and estimates of recent incidence trends have varied widely; studies in the published literature have reported an increase, plateau, and decrease, in age-adjusted incidence rates for hip fracture among both men and women. Accurate characterisation of these temporal trends is important in predicting the health care burden attributable to hip fracture in future decades. We therefore conducted a review of studies worldwide, addressing secular trends in the incidence of hip and other fractures. Studies in western populations, whether in North America, Europe or Oceania, have generally reported increases in hip fracture incidence through the second half of the last century, but those continuing to follow trends over the last two decades have found that rates stabilise, with age-adjusted decreases being observed in certain centres. In contrast, some studies suggest that the rate is rising in Asia. This synthesis of temporal trends in the published literature will provide an important resource for preventing fractures; understanding the reasons for the recent declines in rates of hip fracture may help understand ways to reduce rates of hip fracture worldwide.

Objective: to assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the ?-subunit of the voltage-gated sodium channel Na(V)1.7. Methods: knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy-six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta-analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. Results: no association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of ? = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta-analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta-analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses. Conclusion: we find evidence that the R1150W amino acid change in the Na(V)1.7 ?-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain

OBJECTIVES: To determine patterns of supplement use in a UK community-dwelling older population, and to investigate the extent to which supplement user groups differ, in terms of their sociodemographic and lifestyle characteristics, diet and morbidity. DESIGN: Cross-sectional cohort study. SETTING: Home interview and clinic visit. PARTICIPANTS: 3217 Hertfordshire Cohort Study participants, aged 59 to 73. MEASUREMENTS: Information was obtained on the participant's social and medical history by a trained research nurse. Diet over the preceding 3 months was assessed by Food Frequency Questionnaire; compliance with 'healthy' eating recommendations was defined using individual scores for a 'prudent' dietary pattern, identified using principal components analysis. Details of all dietary supplements taken in the preceding 3 months were recorded. Individual supplements were allocated to one of 10 types based on their nutrient composition. Cluster analysis was used to define groups of supplement users. RESULTS: 45.4% of men and 57.5% of women reported taking at least one dietary supplement in the previous 3 month period. There were 5 distinct clusters of supplement users; these were common to men and women. They were labelled according to the principal supplement taken; oils, glucosamine, single vitamins, vitamins and minerals, and herbal products. These groups differed in their social class and prudent diet score, but few other characteristics. With the exception of a difference in diagnosis of diabetes among the women, there were no differences in morbidity between the supplement groups in either men or women. CONCLUSIONS: Dietary supplement use is high in this population. There are distinct patterns of supplement use, which are related to sociodemographic and lifestyle characteristics including diet, though there were few clear differences in morbidity.

This systematic review and meta-analysis assessed the strength and magnitude of the association between birthweight and adult bone mass. Higher birthweight was associated with higher bone mineral content of the spine and hip in adult men and women at ages between 18 and 80 years across a range of settings. Introduction: The aim of this review was to assess the strength and magnitude of the association between early size and adult bone mass. Methods: Systematic review and meta-analysis of studies that assessed the association between birthweight or weight at 1 year, and bone mineral content (BMC) or bone mineral density (BMD) in adulthood. Results: Fourteen studies met inclusion criteria. Nine assessed the relationship between birthweight and lumbar spine BMC, most showing that higher birthweight was associated with greater adult BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.49 g increase in lumbar spine BMC (95% CI 0.77-2.21). Birthweight was not associated with lumbar spine BMD in 11 studies. In six studies, considering the relationship between birthweight and hip BMC, most found that higher birthweight was associated with greater BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.41 g increase in hip BMC (95% CI 0.91-1.91). Seven studies considered the relationship between birthweight and hip BMD and, in most, birthweight was not a significant predictor of hip BMD. Three studies assessing the relationship between weight at 1 year and adult bone mass all reported that higher weight at one was associated with greater BMC of the lumbar spine and hip. Conclusions: Higher birthweight is associated with greater BMC of the lumbar spine and hip in adulthood. The consistency of these associations, across a range of settings, provides compelling evidence for the intrauterine programming of skeletal development and tracking of skeletal size from infancy to adulthood. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10⁻⁸): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity. © 2009 Nature America, Inc. All rights reserved.

How did the study come about? Ecological studies conducted in the 1980s demonstrated a close geographic correlation between death rates from coronary heart disease during the years 1968–78 in different parts of England and Wales and the infant mortality rate in these areas 60 years earlier.1 These studies suggested that adverse environmental influences acting in utero and during infancy might increase the risk of cardiovascular disease in later life. However, this hypothesis required investigation using more robust epidemiological techniques. To yield results within a relatively short space of time, a cohort study was needed which linked information about the early environment of individuals born at least 60 years earlier to their health outcomes in later life. As part of a nationwide search of archives, staff working at the MRC Environmental Epidemiology Unit (MRC EEU), University of Southampton, discovered a large set of records maintained in Hertfordshire during the early 20th century.

Several studies have shown an association between circulating leptin concentration and bone mineral density. but most studies are cross-sectional in design and report findings in women only. We per-formed a population-based longitudinal study relating baseline plasma leptin concentration to bone mass at the lumbar spine and femoral neck and to change in bone density at these sites over four years in a cohort of 302 men and women aged 60 75 years born and still resident in Hertfordshire, UK. Baseline plasma leptin concentration was strongly positively correlated with body mass index (men: r = 0.71, P 0.0001; women: r = 0.79, P < 0.0001) and with bone mineral content,bone mineral density, and volumetric bone mineral density at all sites (r = 0.24-0.36, P < 0.001) in both sexes: associations with change in bone density were markedly weaker and inconsistent. Adjustment for adult lifestyle determinants of osteoporosis made little difference to our results, but the associations of leptin with bone mass were no longer significant after adjustment for body mass index. These results suggest that the relationship between plasma leptin and bone mass is similar in men and women and that it is mediated through the strong association of both variables with adiposity, rather than through a direct association of leptin on bone cell function.

As matrix metalloproteinases (MMPs) play an important role in rheumatoid arthritis, we investigated whether variation in MMP genes was associated with functional disability in rheumatoid arthritis patients. A cohort of patients with seropositive rheumatoid arthritis were recruited and genotyped for the MMP1-1607 1G > 2G, MMP3-1612 5A > 6A, MMP7-153C > T, MMP7-181G > A, MMP12-82A > G and MMP13-77A > G polymorphisms. Genotypes were then analysed in relation to functional disability assessed by Steinbrocker index and Health Assessment Questionnaire (HAQ) score. We detected an association between the MMP13-77 A > G polymorphism and Steinbrocker index, with patients of the A/A genotype having higher score than patients of the A/G or G/G genotype (P = 0.005), and the association remained significant after adjusting for age, sex, erythrocyte sedimentation rate, presence of erosive disease, Ritchie score, prednisolone therapy and years of diagnosis (P = 0.003). We also observed a relationship of Steinbrocker index with the MMP3-1612 5A > 6A, MMP7-181 A > G and MMP12-82A > G polymorphisms (P = 0.082, P = 0.037 and P = 0.045). No association was detected between the MMP1-1607 1G > 2G and MMP7-153C > T polymorphisms and either Steinbrocker index or HAQ score. These results suggest that MMP3, MMP7, MMP12 and MMP13 genotypes may play a role in determining functional status of rheumatoid arthritis.

The Hertfordshire Cohort Study (HCS) comprises a nationally unique study of 3225 men and women born during the period 1931–39 in the English county of Hertfordshire and still resident there in the late 1990s. The study has previously been described in detail in an IJE Cohort Profile.1 In brief, from 1911 to 1948, health visitors recorded information on birthweight and weight at 1 year on infants born in Hertfordshire. In 1998, those born between 1931 and 1939 were traced through the National Health Service Central Register and a total of 7106 men and women were identified as alive and still resident in the county. Permission to contact these men and women was obtained from their general practitioners. Between 1999 and 2004, they were invited to participate in studies examining the interactions between early life, diet, adult lifestyle and genetic factors as determinants of adult disease. A total of 3225 men and women, aged 59–73 years, were interviewed at home by a trained research nurse who obtained information on the participants' medical and social histories. Subsequently, 2997 men and women attended a clinic for further investigations. Since then, cohort-wide postal follow-up questionnaires and face to face detailed clinical studies of subgroups of the cohort have been conducted. This photoessay describes the history of the HCS across the past 100 years, from instigation of the system that provided us with the historical records that made the study possible to the modern-day high-tech measurement systems that enable us to characterize in detail the health-related outcomes of our cohort members. Photo 1 Ethel Margaret Burnside was the Chief Health Visitor and Lady Inspector of Midwives in Hertfordshire from 1906 to 1919 Photo 2 Miss Burnside set up a system whereby each birth, whether in hospital or at home, was attended by a trained midwife. Records were entered into ledgers that spanned births from 1911 to 1948 Photo 3 The details included type of milk feeding in infancy, weight at 1 year and health in childhood Photo 4 The MRC Lifecourse Epidemiology Unit sought out old records from early life to test the hypothesis that non-communicable diseases have their roots in utero. Some were found in the nick of time! Photo 5 Miss Burnside's records from almost the entire county were found, and are now housed in a purpose-built archive in Southampton. The records began in 1911, and so have reached their centenary Photo 6 Babies born between 1931 and 1939 were traced as adults, and were interviewed at home to characterize their health and well-being Photo 7 Current lifestyle was characterized in detail including assessment of diet using food frequency questionnaires and 24-h food diaries Photo 8 Study members were invited to attend local clinics, the first of which were held at Hertford County Hospital Photo 9 Grip strength was measured by dynamometer as a measure of muscle strength Photo 10 Dual-energy X-ray absorptiometry (DXA) scans were taken to characterize body composition and bone mass Photo 11 Peripheral quantitative computed tomography (pQCT) scans were also taken; this technique uses multiple cross-sectional X-rays to reconstruct a volumetric model of bone density distribution Photo 12 Follow-up studies continue, and regular public engagement events are held

Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. Introduction: We compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW). Methods: GLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures. Results: In total 2,945/43,832 (6.8 %) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95 % confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46 %) or lower than (36 %) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29 % experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities. Conclusions: Postmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

Objective.We sought evidence of association of candidate single nucleotide polymorphisms (SNP) within the growth hormone-insulin-like growth factor 1 (IGF1) axis, largely selected on the basis of functional data available at the time of our study, with adult bone mass.Methods.Four hundred ninety-eight men and 468 women aged 59–71 years were recruited. A lifestyle questionnaire was administered, and bone mineral content (BMC) and bone mineral density (BMD) were measured at the lumbar spine and femoral neck. Two hundred fifty-four men and 271 women had repeat bone densitometry 4 years later. DNA was obtained from whole blood samples using standard extraction techniques. Single nucleotide variants in the growth hormone releasing hormone gene (GHRH, G/A 223 Phe75Leu, rs4988492), growth hormone releasing hormone receptor gene (GHRHR, G/A 217, Ala57Thr, rs4988496), the growth hormone secretagogue receptor gene (GHSR, T/C, Gly57Gly, rs495225), and the growth hormone receptor gene (GHR, T/G, noncoding, rs2940944) were analyzed.Results.In both sexes, allelic variation in the gene encoding GHRH was associated with BMC and BMD at the proximal femur and lumbar spine, with results generally stronger in women. In women, the mean BMC lumbar spine within the GHRH 11 genotype was 56.9 g, while that of the GHRH 12 genotype was 68.4 g [p < 0.001, fully adjusted for age, body mass index, cigarette and alcohol consumption, dietary calcium intake, physical activity, years since menopause, and hormone replacement therapy (HRT) use]; corresponding figures for BMD lumbar spine (GHRH 11 genotype) were 0.96 g/cm2 versus 1.10 g/cm2 (p < 0.001 fully adjusted).Conclusion.We have demonstrated a relationship between allelic variation in the gene encoding GHRH and bone density; we welcome attempts at replication in other populations.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamic-pituitary-adrenal (HPA) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. Maternal smoking, diet (particularly vitamin D deficiency) and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth, are directly linked to the later risk of hip fracture. The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

There has been limited success defining environmental factors important to the development of connective tissue diseases such as systemic lupus erythematosus (SLE). Recent work has suggested that the perinatal environment may be important. To investigate this we measured antinuclear antibodies (ANA) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with ANA positivity in adult life. Included in our investigation were 1334 individuals (668 men, 666 women) from the Hertfordshire cohort study. ANA was measured using an ANA ELISA and confirmed using immunofluorescence. We investigated associations between the presence of ANA and early growth and infectious exposure in infancy in men and women combined, but with adjustment for gender throughout. A positive ANA was present in 73 (10.9%) of men and 81 (12.2%) women. Of these, 26 women and 14 men were positive using IF on HEP2 cells. Sharing a bedroom during childhood was associated with a higher risk of being ANA positive (odds ratio (OR), 1.42, 95% confidence interval (CI) 1.00-2.01, P = 0.05). A record of diarrhoeal illness (OR 2.12 95% CI 1.07, 4.23, P = 0.03) and rubella or mumps during the first year of life (OR 16.12, 95% CI 2.92, 88.94, P = 0.001) was also significantly associated with ANA in adult life. Higher ANA titres by Inova ELISA were associated with infections in the first year of life from mumps (2.74-fold higher, 95% CI 0.98, 7.64, P = 0.05) and rubella (3.90-fold higher, 95% CI 1.89, 8.04, P < 0.001). In addition, higher ANA titres were also associated with mumps (1.26-fold higher, 95% CI 1.02, 1.56, P = 0.03) between one and five years of age. Our results suggest that a developing immune system exposed to increased infection is more likely to produce ANA in adult life and perhaps begin the pathological process that leads to SLE.

Osteoporosis is a major public health issue as well as a considerable socioeconomic burden owing to its association with fragility fractures. Bone mass (a composite of bone size and mineral density) increases through life, from conception to a peak in early adulthood. The magnitude of this peak bone mass is a major determinant of osteoporosis risk in later life. Over the last couple of decades, evidence has accrued that factors in utero and in early life may have persisting influences on later health and disease. Thus, low birthweight is associated with reduced bone density at peak and in older age, and poor infant growth predicts increased risk of hip fracture in later life. Maternal lifestyle, physical activity, body build and, in particular, vitamin D status, appear to be important determinants of intrauterine bone mineral accrual, with a persisting negative influence of maternal vitamin D insufficiency demonstrated at 9 years of age in the offspring. This review examines the impact of maternal nutrition on bone development in offspring and on the later risk of osteoporosis, and suggests that these observations may pave the way for novel population-based public health strategies to reduce the burden of osteoporotic fracture in future generations. © 2009 Future Medicine Ltd.

BACKGROUND: Glucocorticoid use has been associated with an increased fracture risk and reduced bone mineral density (BMD), particularly in the trabecular compartment. However the contribution of the underlying inflammatory disease process to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) typically follows a relapsing-remitting course often requiring recurrent courses of glucocorticoids, but with low systemic inflammation during remission. NS therefore represents a useful clinical model to investigate the effects of glucocorticoids on BMD and bone geometry in childhood. METHODS: Children with NS were compared to age and sex matched healthy controls. Body composition and areal BMD (whole body, lumbar spine and hip) were assessed by DXA. Peripheral quantitative computed tomography (pQCT) scans were obtained at metaphyseal (4%) and diaphyseal (66%) sites of the tibia to determine volumetric BMD and bone cross-sectional geometry. Lifetime cumulative glucocorticoid exposure was calculated from medical records. RESULTS: 29 children with NS (55% male, age 10.7±3.1years) were compared to 29 healthy controls (55% male, age 11.0±3.0years). The children with NS were of similar height SDS to controls (p=0.28), but were heavier (0.65±1.28SDS vs -0.04±0.89SDS, p=0.022) and had greater body fat percentage SDS (0.31±1.01 vs -0.52±1.10, p=0.008). Tibial trabecular and cortical vBMD were similar between the two groups but bone cross-sectional area (CSA) was significantly greater in children with NS at both the metaphysis (954±234mm(2) vs 817±197mm(2), p=0.002) and diaphysis (534.9±162.7mm(2) vs 463.2±155.5mm(2), p=0.014). Endosteal and periosteal circumferences were greater in children with NS than controls (both p

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 population.

Objectives: there has been limited success defining environmental factors important in the development of antiphospholipid (Hughes) syndrome (APS). Recent work suggests that the perinatal environment may be important in the development of other autoimmune diseases. We measured anticardiolipin antibodies (aCL) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with aCL positivity in adult life. Methods: aCLs were measured using an ELISA in 1384 individuals from the Hertfordshire cohort study. We investigated associations between the presence of aCL and early growth and infectious exposure in infancy in men and women. Results: ELISA positive aCL (IgM and IgG) was present in 22 (3%) men and 15 (2%) women. Using the highest octile of aCL results, in men higher birth weight (per lb of birth weight: OR 1.18, 95% CI 1.02–1.36, P = 0.02) and diarrhoeal infection in the first year of life (OR 2.55, 95% CI 1.10, 5.92, P = 0.03) were associated with an increased likelihood of being aCL positive. In women, diarrhoeal infection in the first year of life was also associated with an increased likelihood of aCL positivity (OR 2.23, 95% CI 1.01, 4.91, P = 0.05). For IgG titre in men, significant relationships were found with sharing a bedroom (regression coefficient 1.13; 95% CI 1.05, 1.22; P = 0.02) and diarrhoea in the first year (coefficient 1.25; 95% CI 1.00, 1.56; P = 0.05). Conclusion: a developing immune system when exposed to the infectious environment may influence the likelihood of producing aCL in adult life.

OBJECTIVE: to investigate the relationship between grip strength and health-related quality of life (HRQoL). DESIGN: cross-sectional survey within a cohort study design. SETTING: the county of Hertfordshire in the UK. PARTICIPANTS: a total of 2,987 community-dwelling men and women aged 59-73 years of age. MEASUREMENTS: grip strength was used as a marker of sarcopaenia and measured using a Jamar dynamometer. HRQoL was assessed using the eight domain scores of the Short Form-36 (SF-36) questionnaire, and subjects in the lowest sex-specific fifth of the distribution were classified as having 'poor' status for each domain. RESULTS: men and women with lower grip strength were significantly more likely to report a poor as opposed to excellent to fair overall opinion of their general health (GH) [odds ratio (OR) per kilogram decrease in grip strength = 1.13, 95% CI = 1.06-1.19, P < 0.001 in men, 1.13, 95% CI = 1.07-1.20, P < 0.001 in women]. Among men, after adjustment for age, size, physical activity and known co-morbidity, decreased grip strength was associated with increased prevalence of poor SF-36 scores for the physical functioning (PF) (OR per kilogram decrease in grip strength = 1.03, 95% CI = 1.01-1.06, P = 0.007) and GH domains (OR = 1.03, 95% CI = 1.01-1.05, P = 0.01). Similar associations were seen in women. CONCLUSIONS: our findings suggest that lower grip strength is associated with reduced HRQoL in older men and women. This does not appear to be explained by age, size, physical activity or co-morbidity and may reflect the link between sarcopaenia and generalised frailty. Individuals with sarcopaenia may benefit from interventions to improve muscle mass and strength before the onset of chronic disorders usually associated with impaired HRQoL.