The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial.

BACKGROUND & AIMS: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. METHODS: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. RESULTS: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. CONCLUSION: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. CLINICAL TRIALS REGISTRY: (ACTRN12613000743763).

Association of serum phosphate, calcium and alkaline phosphatase with risk of incident fractures in healthy older adults.

BACKGROUND: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodelling. We examined the associations between levels of phosphate, calcium, and alkaline phosphatase, and fracture risk in initially-healthy older individuals. METHODS: A post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16,703 Australian participants aged ≥70 years and 2,411 US participants aged ≥65 years. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and alkaline phosphatase measurement. Fracture data were collected post-randomization. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). Phosphate, calcium, and alkaline phosphatase were analysed in deciles (D1-D10), with deciles 4-7 (31-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations. RESULTS: Of the 9915 participants, 907 (9·2%) persons had incident fractures recorded over 3·9 (SD 1·4) years. In the fully adjusted model, males in the top decile (D10) of phosphate had 78% higher risk of incident fracture (HR 1·78, 95% CI 1·25-2·54). No such association was observed for females (HR 1·09, 95% CI 0·83-1·44). The population attributable fraction in men within the D10 phosphate category is 6·9%. CONCLUSION: This result confirms that, high-normal serum phosphate levels are associated with increased fracture risk in older men.

Expanding access to fracture liaison services in Australia for people with minimal trauma fractures: a system dynamics modelling study.

OBJECTIVES: To project how many minimal trauma fractures could be averted in Australia by expanding the number and changing the operational characteristics of fracture liaison services (FLS). STUDY DESIGN: System dynamics modelling. SETTING, PARTICIPANTS: People aged 50 years or more who present to hospitals with minimal trauma fractures, Australia, 2020-31. MAIN OUTCOME MEASURES: Numbers of all minimal trauma fractures and of hip fractures averted by increasing the FLS number (from 29 to 58 or 100), patient screening rate (from 30% to 60%), and capacity for accepting new patients (from 40 to 80 per service per month), and reducing the proportion of eligible patients who do not attend FLS (from 30% to 15%); cost per fracture averted. RESULTS: Our model projected a total of 2 441 320 minimal trauma fractures (258 680 hip fractures; 2 182 640 non-hip fractures) in people aged 50 years or older during 2020-31, including 1 211 646 second or later fractures. Increasing the FLS number to 100 averted a projected 5405 fractures (0.22%; $39 510 per fracture averted); doubling FLS capacity averted a projected 3674 fractures (0.15%; $35 835 per fracture averted). Our model projected that neither doubling the screening rate nor reducing by half the proportion of eligible patients who did not attend FLS alone would reduce the number of fractures. Increasing the FLS number to 100, the screening rate to 60%, and capacity to 80 new patients per service per month would together avert a projected 13 672 fractures (0.56%) at a cost of $42 828 per fracture averted. CONCLUSION: Our modelling indicates that increasing the number of hospital-based FLS and changing key operational characteristics would achieve only moderate reductions in the number of minimal trauma fractures among people aged 50 years or more, and the cost would be relatively high. Alternatives to specialist-led, hospital-based FLS should be explored.

Balancing the risks and benefits of sun exposure: A revised position statement for Australian adults.

OBJECTIVE: To describe the development of a new position statement regarding balancing the risks and benefits of sun exposure for Australian adults. METHODS: We conducted a Sun Exposure Summit in March 2021, with presentations from invited experts and a workshop including representation from academic, clinical, policy, and patient stakeholder organisations. The group considered advice about balancing the risks and benefits of sun exposure for Australian adults and developed a revised consensus position statement. RESULTS: The balance of risks and benefits of sun exposure is not the same for everybody. For people at very high risk of skin cancer, the risks of exposure likely outweigh the benefits; sun protection is essential. Conversely, people with deeply pigmented skin are at low risk of skin cancer but at high risk of vitamin D deficiency; routine sun protection is not recommended. For those at intermediate risk of skin cancer, sun protection remains a priority, but individuals may obtain sufficient sun exposure to maintain adequate vitamin D status. CONCLUSIONS: The new position statement provides sun exposure advice that explicitly recognises the differing needs of Australia's diverse population. IMPLICATIONS FOR PUBLIC HEALTH: Mass communication campaigns should retain the focus on skin cancer prevention. The new position statement will support the delivery of personalised advice.

Management of Osteoporosis, Fracture and Falls in People with Multiple Sclerosis: Systematic Review of Guidelines.

People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of osteoporosis, fracture and falls risk may help reduce the burden of musculoskeletal disease in this population. We aimed to systematically review current guidelines regarding osteoporosis prevention, screening, diagnosis and management in people with MS. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic review of scientific databases (MEDLINE, CINAHL, Embase and Scopus) was performed (n = 208). In addition, websites from MS organisations and societies were screened for clinical guidelines (n = 28). Following duplicate removal, screening and exclusions (n = 230), in total six guidelines were included in this review. Three of the identified guidelines were specific to managing osteoporosis in MS, while two linked vitamin D to bone health and one was focused on the effect of acute glucocorticoid use for MS exacerbations on bone health. All guidelines were found to contain inadequate recommendations for osteoporosis screening, management and treatment in people with MS given the evidence of higher prevalence of osteoporosis at an earlier age and compounding risk factors in this population. Early diagnosis and treatment of osteoporosis in people with MS is necessary as fractures lead to significant morbidity and mortality. Development of structured clinical guidelines directed at specific healthcare services will ensure screening, appropriate management, and care of bone health in people with MS.

Femora of women with premature ovarian insufficiency exhibit reduced strength and misalignment with the transmitted vertical forces from the upper body.

BACKGROUND: Women with premature ovarian insufficiency (POI) lack oestrogen, which is a key determinant of bone growth, epiphyseal closure, and bone tissue organisation. Although dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the gold standard for fracture risk evaluation, it does not fully characterise the skeletal abnormalities present in these women. Hence, we aimed to assess hip/femur anatomy, strength, and geometry and femoral alignment using advanced hip analysis (AHA). METHODS: We conducted a cross-sectional, case-control study including 89 women with spontaneous normal karyotype POI (s-POI) or iatrogenic POI (i-POI), aged 20-50 years compared with 89 age- and body mass index (BMI)-matched population-based female controls. Hip anatomy, strength, geometrical parameters, and femur alignment were measured using hip DXA images and Lunar AHA software. Femoral orientation angle (FOA) was quantified as the overall orientation of the femur with respect to the axis of the forces transmitted from the upper body. RESULTS: The median age of POI diagnosis was 35 (18-40) years; the mean POI duration at the time of DXA was 2.07 (range 0-13) years, and 84% of POI women received oestrogen therapy. Areal BMD at all sites was significantly lower in the POI group (all P < .05). Indices of compressive and bending strength were lower in women with POI compared with controls, specifically the cross-sectional area (CSA, mm2) and section modulus (SM, mm3) (139.30 ± 29.08 vs 157.29 ± 22.26, P < .001 and 665.21 ± 129.54 vs 575.53 ± 150.88, P < .001, respectively). The FOA was smaller (124.99 ± 3.18) in women with POI as compared with controls (128.04 ± 3.80; P < .001) at baseline and after adjusting for height and femoral neck BMD. CONCLUSION: Alongside lower BMD at multiple sites, the femora of women with POI demonstrate reduced strength and a misalignment with forces transmitted from the upper body. Further research is needed to establish the role of these newly identified features and their role in fracture risk prediction in this population.

The value of whole-body dual-energy x-ray absorptiometry in assessing body composition in patients with inflammatory bowel disease: a prospective study.

OBJECTIVES: Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged. METHODS: Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150 µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks. RESULTS: Total fat mass was higher in 54 patients with IBD (56% Crohn's disease, 61% male) than in 30 controls (median 25.1 vs. 18.7 kg, P  = 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P  = 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% ( P  = 0.004) and BMI by 6.4% ( P  = 0.012) in 9 responders to therapy. CONCLUSION: DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice.

Australian clinicians' perceptions of patients with very high risk of fracture.

BACKGROUND: International osteoporosis guidelines have recommended treatment approaches based on fracture risk stratification, in particular, anabolic therapy for patients with very high risk (VHR) of fragility fracture. AIM: To summarise Australian clinicians' perceptions of patients at VHR of fracture. METHODS: Australian clinicians invited to educational webinars on anabolic treatments for osteoporosis were surveyed in March and April 2021 about a typical patient they had most recently seen and identified as at VHR of fracture. RESULTS: Of the 268 clinician attendees who were invited to complete the post-webinar surveys, 67 (25%) responded and permitted the publication of aggregated data. A typical patient perceived to have a VHR of fracture was a woman in her 80's, living at home, who had been diagnosed with osteoporosis between 5 and 10 years ago, and received treatment for 1-5 years' duration, most commonly denosumab. The patient frequently had a T-score below -3.0 SD (standard deviation), multiple fragility fractures and most commonly suffered a vertebral fracture in the past 12 months, whereas on an adequate regimen of osteoporosis medication. There was a mismatch between the patient being eligible for anabolic therapy (64.2%) and actually having been prescribed an anabolic treatment in the past (20.9%). CONCLUSIONS: Australian clinicians' perceptions of patients with a VHR of fracture and the use of anabolic agents appear to be heavily influenced by local reimbursement criteria. The mismatch between patients deemed eligible for reimbursed anabolic therapy and those prescribed an anabolic agent suggests treatment inertia.

Bone health in rural Australia: a mixed methods study of consumer needs.

This mixed methods study explores osteoporosis among adults living in a regional area of Victoria, Australia. Three major themes emerged from interviews, which reflected the findings of surveys, concerns regarding the adequacy of care in rural areas, a desire for tailored, local care, and a desire for hybrid telemedicine or in-person services. PURPOSE: Osteoporosis or osteopenia affects over half of adults aged over 50 years. People living outside major cities in Australia have higher hip fracture rates than people living in cities, along with reduced access to bone densitometry and osteoporosis specialists. This study explores osteoporosis risk factors, knowledge, experiences of and preferences for care in people living in a regional area, to inform development of osteoporosis care programs. METHODS: Adults living in a large non-metropolitan region of Australia were invited to participate in a mixed methods study: a survey (phase 1) followed by semi-structured interviews (phase 2) with triangulation of results. Data collected included osteoporosis diagnosis, risk factors, management, knowledge, preferences for care and experience using telemedicine. Surveys were analysed quantitatively, with linear and logistic regression used to assess factors related to osteoporosis knowledge or satisfaction with telemedicine. Interview transcripts were analysed using thematic analysis by two researchers, with in-depth discussion to identify themes. RESULTS: Sixty-two participants completed the survey, and 15 completed interviews. The mean (SD) age of survey participants was 62.2 (14.1) years, 57% had a screening test for osteoporosis, and 12 (19%) had a diagnosis of osteoporosis. The mean osteoporosis knowledge score was 8.4 / 19 and did not differ with age, education, or history of osteoporosis. The majority wanted access to more information about osteoporosis but preferred method differed, and the majority preferred in-person medical consultations to telemedicine. Interview participants were aged between 57 and 87 years, and included 8 with osteoporosis or osteopenia. Three major themes emerged: concerns regarding the adequacy of care in rural areas, a desire for tailored local car and a desire for hybrid telemedicine or in-person services. CONCLUSION: Gaps exist in rural osteoporosis care, including knowledge, screening and management. People have differing experiences of care, access to services and preferences for care. High-quality care, tailored to their needs, was preferred. Improving osteoporosis services for regional Australia will require a flexible, multi-faceted approach, addressing needs of the local community and providers.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

Electrocardiogram Changes Following Intravenous Bisphosphonate Infusion: A Systematic Review and Meta-Analysis.

Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients receiving bisphosphonates; however, uncertainty remains as to whether electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting electrocardiogram (ECG) findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE from inception until January 14, 2023, for studies reporting ECG parameters after intravenous bisphosphonate infusion. We excluded studies that only reported atrial fibrillation. Study quality was assessed using the Newcastle-Ottawa scale. Continuous data were meta-analyzed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95% CIs). We found 1083 unique records, of which 11 met our inclusion and exclusion criteria. Studies had a low to low/moderate risk of bias. Six prospective cohort studies were included in the meta-analysis. Five studies used zoledronic acid, whereas one study used pamidronate. Most studies (n = 4) were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases, and one study in children with osteoporosis secondary to cerebral palsy. Study populations ranged from n = 15 to n = 116. Heart rate-corrected QT (QTc) was significantly longer post-infusion (SMD = 0.46 ms [95% CI 0.80 to 0.11]; n = 67 patients, k = 2 studies, τ2 = 0). There were no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc, QTc (maximum), QTc (minimum), and QTc dispersion. The correlation between pre- and post-infusion QTc was not significant (p = 0.93). Overall, there is a weak association between intravenous bisphosphonate infusion and a QTc interval prolongation. However, there is insufficient evidence to support an association between intravenous bisphosphonate and any ECG variable changes, which may precipitate atrial fibrillation. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Novel RUNX1 Genetic Variant Identified in a Young Male with Severe Osteoporosis.

This case describes a young man with an unusual cause of severe osteoporosis and markedly deranged bone microarchitecture resulting in multiple fractures. A potentially pathogenic germline variant in the runt-related transcription factor 1 (RUNX1) gene was discovered by a focused 51-gene myeloid malignancy panel during investigation for his unexplained normochromic normocytic anemia. Further bone-specific genetic testing and a pedigree analysis were declined by the patient. Recent experimental evidence demonstrates that RUNX1 plays a key role in the regulation of osteogenesis and bone homeostasis during skeletal development, mediated by the bone morphogenic protein and Wnt signaling pathways. Therefore, rarer causes of osteoporosis, including those affecting bone formation, should be considered in young patients with multiple unexpected minimal trauma fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial.

Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.

Effects of Moderate- to High-Impact Exercise Training on Bone Structure Across the Lifespan: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Moderate- to high-impact exercise improves bone mineral density (BMD) across the lifespan, but its effects on bone structure, which predicts fracture independent of areal BMD, are unclear. This systematic review and meta-analysis investigated effects of impact exercise on volumetric BMD (vBMD) and bone structure. Four databases (PubMed, Embase, SPORTDiscus, Web of Science) were searched up to March 2022 for randomized controlled trials (RCTs) investigating the effects of impact exercise, with ground reaction forces equal to or greater than running, compared with sham or habitual activity, on bone vBMD and structure. Bone variables were measured by quantitative computed tomography or magnetic resonance imaging at the tibia, radius, lumbar spine, and femur. Percentage changes in bone variables were compared among groups using mean differences (MD) and 95% confidence intervals (CI) calculated via random effects meta-analyses. Subgroup analyses were performed in children/adolescents (<18 years), adults (18-50 years), postmenopausal women, and older men. Twenty-eight RCTs (n = 2985) were included. Across all studies, impact exercise improved trabecular vBMD at the distal tibia (MD = 0.54% [95% CI 0.17, 0.90%]), total vBMD at the proximal femur (3.11% [1.07, 5.14%]), and cortical thickness at the mid/proximal radius (1.78% [0.21, 3.36%]). There was no effect on vBMD and bone structure at the distal radius, femoral shaft, or lumbar spine across all studies or in any subgroup. In adults, impact exercise decreased mid/proximal tibia cortical vBMD (-0.20% [-0.24, -0.15%]). In postmenopausal women, impact exercise improved distal tibia trabecular vBMD (0.79% [0.32, 1.25%]). There was no effect on bone parameters in children/adolescents in overall analyses, and there were insufficient studies in older men to perform meta-analyses. Impact exercise may have beneficial effects on bone structure and vBMD at various skeletal sites, but additional high-quality RCTs in different age and sex subgroups are needed to identify optimal exercise protocols for improving bone health across the lifespan. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Fracture Risk Increases After Stroke or Transient Ischemic Attack and Is Associated With Reduced Quality of Life.

BACKGROUND: Fractures are a serious consequence following stroke, but it is unclear how these events influence health-related quality of life (HRQoL). We aimed to compare annualized rates of fractures before and after stroke or transient ischemic attack (TIA), identify associated factors, and examine the relationship with HRQoL after stroke/TIA. METHODS: Retrospective cohort study using data from the Australian Stroke Clinical Registry (2009-2013) linked with hospital administrative and mortality data. Rates of fractures were assessed in the 1-year period before and after stroke/TIA. Negative binomial regression, with censoring at death, was used to identify factors associated with fractures after stroke/TIA. Respondents provided HRQoL data once between 90 and 180 days after stroke/TIA using the EuroQoL 5-dimensional 3-level instrument. Adjusted logistic regression was used to assess differences in HRQoL at 90 to 180 days by previous fracture. RESULTS: Among 13 594 adult survivors of stroke/TIA (49.7% aged ≥75 years, 45.5% female, 47.9% unable to walk on admission), 618 fractures occurred in the year before stroke/TIA (45 fractures per 1000 person-years) compared with 888 fractures in the year after stroke/TIA (74 fractures per 1000 person-years). This represented a relative increase of 63% (95% CI, 47%-80%). Factors associated with poststroke fractures included being female (incidence rate ratio [IRR], 1.34 [95% CI, 1.05-1.72]), increased age (per 10-year increase, IRR, 1.35 [95% CI, 1.21-1.50]), history of prior fracture(s; IRR, 2.56 [95% CI, 1.77-3.70]), and higher Charlson Comorbidity Scores (per 1-point increase, IRR, 1.18 [95% CI, 1.10-1.27]). Receipt of stroke unit care was associated with fewer poststroke fractures (IRR, 0.67 [95% CI, 0.49-0.93]). HRQoL at 90 to 180 days was worse among patients with prior fracture across the domains of mobility, self-care, usual activities, and pain/discomfort. CONCLUSIONS: Fracture risk increases substantially after stroke/TIA, and a history of these events is associated with poorer HRQoL at 90 to 180 days after stroke/TIA.

The effect of vitamin D supplementation on the gut microbiome in older Australians - Results from analyses of the D-Health Trial.

Observational studies suggest a link between vitamin D and the composition of the gut microbiome, but there is little evidence from randomized controlled trials of vitamin D supplementation. We analyzed data from the D-Health Trial, a randomized, double-blind, placebo-controlled trial. We recruited 21,315 Australians aged 60-84 y and randomized them to 60,000 IU of vitamin D3 or placebo monthly for 5 y. Stool samples were collected from a sample of 835 participants (417 in the placebo and 418 in the vitamin D group) approximately 5 y after randomization. We characterized the gut microbiome using 16S rRNA gene sequencing. We used linear regression to compare alpha diversity indices (i.e. Shannon index (primary outcome), richness, inverse Simpson index), and the ratio of Firmicutes to Bacteroidetes between the two groups. We analyzed between-sample (beta) diversity (i.e. Bray Curtis distance and UniFrac index) using principal coordinate analysis and used PERMANOVA to test for significant clustering according to randomization group. We also assessed the difference in the abundance of the 20 most abundant genera between the two groups using negative binomial regression model with adjustment for multiple testing. Approximately half the participants included in this analysis were women (mean age 69.4 y). Vitamin D supplementation did not alter the Shannon diversity index (mean 3.51 versus 3.52 in the placebo and vitamin D groups, respectively, p = 0.50). Similarly, there was little difference between the groups for other alpha diversity indices, the abundance of different genera, and the Firmicutes-to-Bacteroidetes ratio. We did not observe clustering of bacterial communities according to randomization group. In conlusion, monthly doses of 60,000 IU of vitamin D supplementation for 5 y did not alter the composition of the gut microbiome in older Australians.

Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.

OBJECTIVE: To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events. DESIGN: Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments. SETTING: Australia from 2014 to 2020. PARTICIPANTS: 21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment. INTERVENTION: 60 000 IU/month vitamin D3 (n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%). MAIN OUTCOME MEASURES: The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: 21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was -5.8 events per 1000 participants (95% confidence interval -12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23). CONCLUSIONS: Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease. TRIAL REGISTRATION: ACTRN12613000743763.

Accuracy of ultrasound, bioelectrical impedance analysis and anthropometry as point-of-care measurements of skeletal muscle mass in patients with inflammatory bowel disease.

BACKGROUND: Disturbance of skeletal muscle mass has clinically important implications in patients with inflammatory bowel disease (IBD), but accurate quantification requires radiation-intense techniques. AIMS: We aimed to compare point-of-care muscle assessments and their change with therapy with those using reference-standard whole-body dual energy X-ray absorptiometry (DXA). METHODS: Adult patients with IBD and healthy controls underwent prospective assessment of muscularity by ultrasound of the dominant arm and both thighs, bioelectrical impedance analysis (BIA), anthropometric measurements, and DXA. Patients with active IBD were assessed again ≥13 weeks after initiating biologic induction therapy. RESULTS: In 54 patients with IBD and 30 controls, all muscle assessments correlated significantly with DXA-derived skeletal muscle index (SMI). In IBD, ultrasound of the arm and legs had the best agreement with DXA-derived SMI (mean difference 0 kg/m2 , 95% limits of agreement -1.3 to 1.3), while BIA overestimated DXA-derived SMI by 1.07 (-0.16 to +2.30) kg/m2 . In 17 patients who underwent biologic therapy, the percentage change in DXA-derived SMI correlated significantly with the percentage change in all other muscle assessment techniques. Responders (n = 9) increased SMI from baseline to follow-up when derived from DXA (mean 7.8-8.5 kg/m2 , p = 0.004), ultrasound of the arm and legs (300-343 cm2 , p = 0.021) and BIA (9.2-9.6 kg/m2 , p = 0.011). CONCLUSIONS: Ultrasound of the arm and legs out-performed other point-of-care methods in its accuracy of measuring muscle mass. All methods, except mid-arm circumference, were responsive to therapy-induced change. Ultrasound is the preferred non-invasive test for measuring muscle mass in patients with IBD.