Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

BACKGROUND: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. METHODS: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. RESULTS: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. CONCLUSION: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study.

(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25-50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0-110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = -59.9--7.5, B = -33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.

The Association between 25-Hydroxyvitamin D Concentration and Disability Trajectories in Very Old Adults: The Newcastle 85+ Study.

Background: Low vitamin D status is common in very old adults which may have adverse consequences for muscle function, a major predictor of disability. Aims: To explore the association between 25-hydroxyvitamin D [25(OH)D] concentrations and disability trajectories in very old adults and to determine whether there is an 'adequate' 25(OH)D concentration which might protect against a faster disability trajectory. Methodology: A total of 775 participants from the Newcastle 85+ Study for who 25(OH)D concentration at baseline was available. Serum 25(OH)D concentrations of <25 nmol/L, 25-50 nmol/L and >50 nmol/L were used as cut-offs to define low, moderate and high vitamin D status, respectively. Disability was defined as difficulty in performing 17 activities of daily living, at baseline, after 18, 36 and 60 months. Results: A three-trajectory model was derived (low-to-mild, mild-to-moderate and moderate-to-severe). In partially adjusted models, participants with 25(OH)D concentrations <25 nmol/L were more likely to have moderate and severe disability trajectories, even after adjusting for sex, living in an institution, season, cognitive status, BMI and vitamin D supplement use. However, this association disappeared after further adjustment for physical activity. Conclusions: Vitamin D status does not appear to influence the trajectories of disability in very old adults.

Feasibility and acceptability of a milk and resistance exercise intervention to improve muscle function in community-dwelling older adults (MIlkMAN): Pilot study.

BACKGROUND: Dietary protein supplementation combined with resistance exercise (RE) may counteract declines in muscle strength, mass, and function (sarcopenia), but the role of whole foods rich in protein, such as milk, is less well understood. In the MIlkMAN study, we aimed to examine the feasibility and acceptability of milk+RE as an intervention for muscle function in community-dwelling older adults, and provide exploratory pilot data for future substantive research in population at risk of sarcopenia. METHODS: In a parallel groups design, 30 older adults (71.7±3.6 years; 12 women) were randomised into three groups: WM (whole milk 3.6% fat)+RE, SM (skimmed milk 0.3% fat)+RE, and C (isocaloric carbohydrate drink)+RE. RE was performed twice-weekly over 6 weeks in a community gym, followed by the consumption of 500 ml of milk (~20 g protein) or carbohydrate drink immediately after exercise and a further 500 ml at home within the following 4-5 hours. The feasibility and acceptability of the study was determined by calculating recruitment and attendance rates, compliance with the intervention, rating participants' experiences, and recording adverse health events. RESULTS: The response rate was 49% (out of 400 invitations sent), and the recruitment rate was 73.2% (30 participants recruited out of 41 screened for eligibility). Twenty-nine participants completed the intervention-an attendance rate of 97.1%; 89.7% rated their experience as 'excellent'/very good'. Compliance with taking the drinks was 97.1% (WM), 98.3% (SM), and 95.0% (C); 93.1% rated their drink intake as 'easy'/'very easy' with no adverse effects. Collection of exploratory pilot data to inform future trials was successful. Mean change in grip strength, 5-chair rises, and gait speed were 0.9±3.4 kg, 1.8±2.2 s, 0.1±0.1 m/s, respectively with no differences between the groups. CONCLUSIONS: This community-based milk+RE intervention was feasible and acceptable to older adults. The study successfully collected pilot data for future substantive research.

Milk for Skeletal Muscle Health and Sarcopenia in Older Adults: A Narrative Review.

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50-99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging.

Study of the Older Adults' Motivators and Barriers Engaging in a Nutrition and Resistance Exercise Intervention for Sarcopenia: An Embedded Qualitative Project in the MIlkMAN Pilot Study.

Objectives: The present study aimed to investigate motivators and barriers to older adults engaging in a nutrition and resistance exercise (RE) intervention for sarcopenia. Methods: We conducted a content analysis of structured interviews with 29 community-dwelling older adults (aged 65-80 years) completing the MIlk Intervention Muscle AgeiNg (MIlkMAN) study. Results: Content analysis revealed that self-perceived improved health, knowledge acquisition in nutrition and exercise, social well-being, professional support in a fun environment, and positive reported outcomes were motivators for engagement in the intervention. Peer encouragement, social bonds, and their retention were motivators to continuing engagement after study completion, especially in widowed women. Barriers to maintenance included affordability, environmental factors, and concerns over negative health outcomes. Discussion: Nutrition and RE interventions for sarcopenia should focus on knowledge acquisition about their health benefits, being enjoyable, and offering social opportunities that have the potential to last beyond the study duration to promote and maintain positive health behaviors.

Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

BACKGROUND: On stopping bisphosphonate treatment, bone resorption may increase before evidence of a decrease in bone density. Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday. METHODS: Retrospective analysis of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at discontinuation (baseline), n=138 and 4 months and n=136, and 12 months (n=100). Premenopausal mean CTX levels and the least significant change (LSC) detectable were used to define target thresholds for bone turnover. RESULTS: Following long-term bisphosphonate treatment (69% alendronic acid, 33% risedronate, mean duration 8 years SD 2.7), 32% patients had CTX above target (0.19 µg/L). In those with baseline CTX below threshold, 28% increased CTX to >0.19 µg/L and > LSC (0.06 µg/L) by 4 months (mean CTX increase 0.05 µg/L [95% confidence interval (CI): 0.04-0.06; p<0.0001]) and 53% by 12 months (mean CTX increase 0.09 µg/L [95% CI: 0.07-0.10; p<0.0001]), whilst 47% had no detectable changes in CTX over 12 months. CONCLUSION: A third of patients showed inadequate suppression of CTX at baseline, despite long-term bisphosphonate treatment. Drug holiday may not be appropriate for this group, showing a poor therapeutic response or poor adherence. For more than a quarter of patients, bisphosphonate effects were wearing off at 4 months and around half by 12 months. We suggest CTX monitoring could identify those not experiencing a sustained bisphosphonate effect, including poorly adherence to therapy, and may be used during a drug holiday to prompt recommencement of therapy.

Milk and resistance exercise intervention to improve muscle function in community-dwelling older adults at risk of sarcopenia (MIlkMAN): protocol for a pilot study.

INTRODUCTION: Sarcopenia is a progressive muscle disorder characterised by decline in skeletal muscle mass, strength and function leading to adverse health outcomes, including falls, frailty, poor quality of life and death. It occurs more commonly in older people and can be accelerated by poor diet and low physical activity. Intervention studies incorporating higher dietary protein intakes or protein supplementation combined with resistance exercise (RE) have been shown to limit muscle function decline. However, less is known about the role of whole foods in reducing the risk of sarcopenia. Milk is a source of high-quality nutrients, which may be beneficial for skeletal muscle. This pilot study examines the feasibility and acceptability of milk consumption with RE to improve muscle function in community-dwelling older adults at risk of sarcopenia. METHODS AND ANALYSIS: 30 older adults aged ≥65 years will be randomly allocated to three groups: 'whole milk+RE', 'skimmed milk+RE' or 'control drink+RE'. Assessments will take place in participants' homes, including screening (milk allergies, grip strength, walking speed), baseline and postintervention health and function. All participants will undertake a structured RE intervention twice a week for 6 weeks at a local gym, followed by the consumption of 500 mL of whole or skimmed milk (each ~20 g of protein) or an isocaloric control drink and another 500 mL at home. Participants' views about the study will be assessed using standardised open-ended questions. The primary outcomes include feasibility and acceptability of the intervention with recruitment, retention and intervention response rates. Analyses will include descriptive statistics, exploration of qualitative themes and intervention fidelity. ETHICS AND DISSEMINATION: Outputs include pilot data to support funding applications; public involvement events; presentation at conferences and peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN13398279; Pre-results.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Osteoporosis and the Ageing Skeleton.

Osteoporosis is a "skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture" which, in light of demographic change, is becoming an increasing burden on health care worldwide. Increasing age and female gender are associated with the condition, although a wider range of clinical risk factors are being used increasingly to identify those at risk of osteoporosis and its most important sequelae, fracture.While osteoporosis and fracture have long been associated with women in the post-menopausal age, fracture incidence increases because of the ageing of our population. Interventions to abate the progression of osteoporosis and to prevent fractures must focus on the old and the very old. Evidence associating nutritional factors, particularly calcium and vitamin D are reviewed as are the association of falls risk with fracture and the potential for interventions to prevent falls. Finally, the assessment of frailty in the oldest old, associated sarcopenia and multi-morbidity are considered in the evaluation of fall and fracture risk and the management of osteoporosis in the ninth decade of life and beyond.

Does domiciliary welfare rights advice improve health-related quality of life in independent-living, socio-economically disadvantaged people aged ≥60 years? Randomised controlled trial, economic and process evaluations in the North East of England.

BACKGROUND: There are major socio-economic gradients in health that could be influenced by increasing personal resources. Welfare rights advice can enhance resources but has not been rigorously evaluated for health-related impacts. METHODS: Randomised, wait-list controlled trial with individual allocation, stratified by general practice, of welfare rights advice and assistance with benefit entitlements, delivered in participants' homes by trained advisors. Control was usual care. Participants were volunteers sampled from among all those aged ≥60 years registered with general practices in socio-economically deprived areas of north east England. Outcomes at 24 months were: CASP-19 score (primary), a measure of health-related quality of life; changes in income, social and physical function, and cost-effectiveness (secondary). Intention to treat analysis compared outcomes using multiple regression, with adjustment for stratification and key covariates. Qualitative interviews with purposive samples from both trial arms were thematically analysed. FINDINGS: Of 3912 individuals approached, 755 consented and were randomised (381 Intervention, 374 Control). Results refer to outcomes at 24 months, with data available on 562 (74.4%) participants. Intervention was received as intended by 335 (88%), with 84 (22%) awarded additional benefit entitlements; 46 did not receive any welfare rights advice, and none of these were awarded additional benefits. Mean CASP-19 scores were 42.9 (Intervention) and 42.4 (Control) (adjusted mean difference 0.3 [95%CI -0.8, 1.5]). There were no significant differences in secondary outcomes except Intervention participants reported receiving more care at home at 24m (53.7 (Intervention) vs 42.0 (Control) hours/week (adjusted mean difference 26.3 [95%CIs 0.8, 56.1]). Exploratory analyses did not support an intervention effect and economic evaluation suggested the intervention was unlikely to be cost-effective. Qualitative data from 50 interviews suggested there were improvements in quality of life among those receiving additional benefits. CONCLUSIONS: We found no effects on health outcomes; fewer participants than anticipated received additional benefit entitlements, and participants were more affluent than expected. Our findings do not support delivery of domiciliary welfare rights advice to achieve the health outcomes assessed in this population. However, better intervention targeting may reveal worthwhile health impacts.

Randomized controlled trial of vitamin D supplementation in older people to optimize bone health.

Background: Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results. Objectives: This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry. Methods: A total of 379 adults aged ≥70 y (48% women; mean age: 75 y) from the northeast of England were randomly allocated to 1 of 3 doses of vitamin D3 [12,000 international units (IU), 24,000 IU, or 48,000 IU] given once a month. The primary outcome was change in BMD (ΔBMD) at the hip. Secondary endpoints comprised the dose effects on femoral neck BMD, falls, circulating calciotropic hormones, bone turnover markers, and adverse events. Results: The mean ± SD baseline plasma 25-hydroxyvitamin D [25(OH)D] concentration was 40.0 ± 20.1 nmol/L, which increased after 12 mo to a mean 25(OH)D of 55.9, 64.6, or 79.0 nmol/L for participants receiving a monthly dose of 12,000, 24,000, or 48,000 IU, respectively (P < 0.01 for difference). There was no between-group difference in ΔBMD. However, parathyroid hormone concentrations decreased in all 3 groups, with a significantly greater decrease in the 48,000-IU group compared with the 12,000-IU group (P < 0.01). There were no differences in any adverse events between groups, with 3 cases of hypercalcemia, none of nephrolithiasis, and 249 falls observed. Conclusions: There was no difference in change in BMD over 12 mo between the 3 doses of vitamin D, suggesting no effect of the intervention or a similar attenuation of the anticipated decrease in BMD over 12 mo. The treatment was safe and effective in increasing plasma 25(OH)D concentrations, with no dose-related adverse events. This trial was registered at the EU Clinical Trials Register (EudraCT 2011-004890-10) and the ISRCTN Registry (ISRCTN35648481).

Implications of guidelines for osteoporosis and its treatment.

The development of clinical guidelines is now a more uniform process, with formalised methods to ensure that recommendations are based on current best available evidence from randomised controlled trials and systematic reviews. Over the past 20 years we have seen a growth in guidelines including those relating to osteoporosis, with recommendations varying between and within countries. Some guidelines are concerned with case finding and primary or secondary prevention, such as those produced by the National Institute for Health and Care Excellence (NICE CG146, TA-160, -161, -464), while others focus on specific conditions or risk factors associated with osteoporosis, such as the menopause, coeliac disease and eating disorder. Clinicians can be confused as to which to follow in any particular clinical scenario. International guidelines, such as those from North America (NOF, CAROC, AACE) and Scotland (SIGN 142), differ from those of England, Wales and Northern Ireland, with recent recommendations from NICE (TA464) shifting the focus of treatment from those at greatest fracture risk to an apparent blanket approach, based on cost-effectiveness, rather than clinical effectiveness.Osteoporosis treatment should be targeted at those who can benefit most, outweighing the potential for harm. If the low health economic threshold of NICE TA464 were adopted as a clinical threshold, the most important group-older people at greatest risk of fracture, would not be prioritised. We risk overwhelming clinical services, while causing harm to some at low fracture risk from adverse effects of treatment, yet failing to treat the older population at highest fracture risk.

Assessing the need for arthritis training among paid carers in UK residential care homes: A focus group and interview study.

OBJECTIVE: The aim of the study was to perform an educational and training needs assessment for arthritis care in residential homes. METHODS: Qualitative data were collected from three purposively selected residential homes: one independent, one in a regional chain and one in a national chain. Three researcher-led focus groups were conducted with paid carers (N = 22) using vignette exercises; interviews were undertaken with 12 residents with joint pain (N = 12), five managerial staff and two general practitioners (GPs). Data were compared and analysed thematically around care practices, communication and training. RESULTS: There is a lack of arthritis awareness among paid carers, although they regularly identify and manage arthritic symptoms. Residents rely on paid carers to recognize when pain and mobility problems are treatable. Senior staff and GPs rely on carers to identify arthritic problems. However, paid carers themselves undervalued the health significance of their activities and lacked the confidence to communicate important information to healthcare professionals. Few of the paid carers had received training in arthritis and many expressed a strong desire to learn about it, to improve their ability to provide better care. CONCLUSIONS: Education for paid carers regarding arthritis is lacking and lags behind education about conditions such as dementia and diabetes. To meet the expectations of their care roles fully, paid carers require an awareness of what arthritis is and how to recognize symptoms. We suggest that training should be aimed at improving confidence in communicating with colleagues, residents and health professionals, with senior care staff receiving more in-depth training.

The Role of Vitamin D in Disease Progression in Early Parkinson's Disease.

BACKGROUND: Previous cross-sectional studies have shown that Parkinson's disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients. OBJECTIVE: The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period. METHODS: A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, n = 145; control, n = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study. RESULTS: Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1±21.7 vs. 52.2±22.1 nmol/L, p < 0.05) and 18 months (44.2±23.6 vs. 55.7±28.8 nmol/L, p < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months ((ΔR2 = 0.039, F = 6.6, p < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period. CONCLUSIONS: Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months.