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  • Different Indices of Fetal Growth Predict Bone Size and Volumetric Density at 4 Years Old.

    18 September 2018

    Abstract We have previously demonstrated that higher birth-weight is associated with greater peak and later life bone mineral, and that maternal body build, diet and lifestyle influence prenatal bone mineral accrual. To examine further prenatal influences on bone health we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19-34 weeks gestation from ultrasound measurements in participants in the Southampton Women's Survey. 380 of the offspring underwent dual-energy X-ray absorptiometry at age 4-years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD) and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height and weight. A higher velocity of 19-34 week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r=0.30, p<0.0001) but not with volumetric density (vBMD: r=0.03, p=0.51). Conversely, a higher velocity of 19-34 week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r=0.15, p=0.004) but not with skeletal size (BA: r=0.06, p=0.21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19-34 weeks gestation predicted childhood skeletal size at age 4-years whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.

  • The epidemiology of osteoporotic fractures

    18 September 2018

    Osteoporosis is a major public health issue affecting a large proportion of the population aged over fifty years. It leads to a huge burden through the increased morbidity and mortality associated with fragility fractures. Although the age-specific incidence of fractures has been increasing over the last 40 years in the West, this now seems to be plateauing. However, with the predicted increase in the world population, particularly the over 65's, over the next 40 years, the future burden of fractures will increase substantially. There is a large genetic component to peak bone mass, which is polygenic in origin. Increasingly it is recognised that environmental factors not only affect the rate of bone loss, but also affect peak bone mass gained. This has led to a new approach, based on the idea of "foetal programming". Patient assessment has, in the past, been based on bone mineral density and the relative risk of fracture. New approaches involve determining a patient's 5-10 year absolute risk of fracture, which will allow better targeting of today's more effective but expensive treatments.

  • Physical activity in former elite cricketers and strategies for promoting physical activity after retirement from cricket: a qualitative study.

    18 September 2018

    OBJECTIVES: The health benefits of professional sport dissipate after retirement unless an active lifestyle is adopted, yet reasons for adopting an active or inactive lifestyle after retirement from sport are poorly understood. Elite cricket is all-encompassing, requiring a high volume of activity and unique physical demands. We aimed to identify influences on physical activity behaviours in active and insufficiently active former elite cricketers and provide practical strategies for promoting physical activity after cricket retirement. DESIGN: 18 audio-recorded semistructured telephone interviews were performed. An inductive thematic approach was used and coding was iterative and data-driven facilitated by NVivo software. Themes were compared between sufficiently active and insufficiently active participants. SETTING: All participants formerly played professional cricket in the UK. PARTICIPANTS: Participants were male, mean age 57±11 (range 34-77) years, participated in professional cricket for 12±7 seasons and retired on average 23±9 years previously. Ten participants (56%) were classified as sufficiently active according to the UK Physical Activity Guidelines (moderate-intensity activity ≥150 min per week or vigorous-intensity activity ≥75 min per week). Eight participants did not meet these guidelines and were classified as insufficiently active. RESULTS: Key physical activity influences were time constraints, habit formation, intrinsic and extrinsic motivation, physical activity preferences, pain/physical impairment and cricket coaching. Recommendations for optimising physical activity across the lifespan after cricket retirement included; prioritise physical activity, establish a physical activity plan prior to cricket retirement and don't take a break from physical activity, evaluate sources of physical activity motivation and incorporate into a physical activity plan, find multiple forms of satisfying physical activity that can be adapted to accommodate fluctuations in physical capabilities across the lifespan and coach cricket. CONCLUSIONS: Physically active and less active retired cricketers shared contrasting attributes that informed recommendations for promoting a sustainable, physically active lifestyle after retirement from professional cricket.

  • Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

    18 September 2018

    BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

  • Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti-TNF therapy.

    18 September 2018

    BACKGROUND: Inhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability. METHODS: Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI). RESULTS: 31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C-reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant. CONCLUSIONS: Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.

  • Training the next generation of clinical researchers: evaluation of a graduate podiatrist research internship in rheumatology.

    18 September 2018

    BACKGROUND: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. METHODS: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. RESULTS: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees.Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. CONCLUSIONS: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales.