Osteoporosis and fracture risk assessment in adults with ischaemic stroke.

PURPOSE: To study the prevalence of osteoporosis, falls and fractures in adults with ischaemic stroke. METHODS: Observational cohort study of adults aged ≥ 50 years admitted with ischaemic stroke over a 12-month period were invited to participate in a telephone interview one-year post-stroke to ascertain falls and fracture. A Fracture Risk After Ischaemic Stroke (FRAC-stroke) score was calculated. RESULTS: Of the 1267 patients admitted to the stroke unit between 1 January 2020 and 31 December 2020, 624 had a modified Rankin Score documented. Of these, 316 adults ≥ 50 years had ischaemic stroke and 131 consented to a telephone interview. Mean age was 72.4 ± 10.7 years and 36.6% were female. 34 patients (25.9%) had a FRAC-stroke score of ≥ 15, equating to ≥ 5% risk of fracture in the year following stroke. Eleven (8.4%) patients (6 female) had a minimal trauma fracture in the 12 months post-stroke. There was a significant difference in patients experiencing falls pre- and post-stroke (19.8% vs 31.3%, p = 0.04). FRAC-stroke score was higher in those who had a fracture post stroke compared those who did not (20.4 vs 8.9, p < 0.001). Receiver operating characteristic analysis found an area under the curve of 0.867 for FRAC-stroke score (95% CI 0.785-0.949, p < 0.005). The optimal cutoff value for FRAC-stroke score predicting fracture was 12 with a sensitivity of 90.9% and specificity of 70%. CONCLUSION: The FRAC-stroke score is a simple clinical tool that can be used to identify patients at high risk of fracture post-stroke who would most benefit from osteoporosis therapy. Stroke is a risk factor for fracture due to immobilisation, vitamin D deficiency and increased falls risk. This study found that a simple bedside tool, the FRAC-stroke score, can predict fracture after ischaemic stroke. This will allow clinicians to plan treatment of osteoporosis prior to discharge from a stroke unit.

IOF position on scientists and societies operating in conflict zones.

This position paper of the International Osteoporosis Foundation reports the findings of an IOF Commission to consider to recommend rules of partnership with scientists belonging to a country which is currently responsible for an armed conflict, anywhere in the world. The findings and recommendations have been adopted unanimously by the Board of IOF.

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.

Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFÉ£ on human gingival mesenchymal stem cells properties.

AIMS: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes. METHODS: Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1ß[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 µg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR. RESULTS: G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p > .05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10-5 (Q25/Q75)] were utmost in control - [2.6607 (2.0804/4.5357)], followed by cytokine - [0.0433 (0.0026/1.4215)] and significantly lowered in the oxLDL group [0.0274 (0.0023/0.7290); p = .0047]. Osteogenic differentiation [median relative Ca2+ content(Q25/Q75)] was significantly lower in cytokine - [0.0066 (0.0052/0.0105)] compared to oxLDL - [0.0144 (0.0108/0.0216)] (p = .0133), with no differences notable for chondrogenic and adipogenic differentiation (p > .05). CONCLUSIONS: Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.

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.

Challenges for trainee physician-scientists during their PhD candidature: a cross-sectional study.

BACKGROUND: Physician-scientists are important drivers of research, in both knowledge acquisition and research translation. In Australia, many newly qualified physicians and advanced physician trainees enrol in PhD studies, with a view to training as physician-scientists. However, data on perceived challenges and ways to support them are limited. METHODS: This single-centre study surveyed trainee physician-scientists undertaking PhD studies within the Monash University Department of Medicine in 2020. Following discussions with PhD students and a qualitative written questionnaire, trainee physician-scientists were invited to complete a quantitative survey that aimed to identify current and future career challenges and determine the type of enrichment and support mechanisms they value most and would most likely use. RESULTS: From 45 eligible participants, 25 responses were received (76% female). Participants identified multiple substantial challenges (median of 6) during their candidature relating to their project, changes in roles and their personal lives. They also envisaged future challenges post-PhD in establishing themselves as an independent investigator, further changes in their identity and their personal lives. Of potential support mechanisms during their candidature, a mentoring program was the most favoured, with an online discussion forum being the least popular. CONCLUSIONS: Trainee physician-scientists report multiple challenges during their PhD candidature and envisage significant challenges in establishing their research independence after PhD completion. They valued several potential support mechanisms, particularly a mentoring program. Australian universities and their associated academic health services should consider establishing programs to support trainee physician-scientists.

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.

Recommendations for the optimal use of bone forming agents in osteoporosis.

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.

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.

Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults.

PURPOSE: Observational studies suggest that higher serum 25-hydroxy vitamin D (25(OH)D) concentration may be associated with lower risk of cataract. However, no randomized controlled trials have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. DESIGN: We conducted an ancillary study of the D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D conducted from 2014 through 2020 within the Australian general population. PARTICIPANTS: We invited 421 207 men and women 60 to 84 years of age to participate; including an additional 1896 volunteers, 40 824 expressed interest. Those with hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis or those who were taking more than 500 international units (IU) supplemental vitamin D per day were excluded. A total of 21 315 were randomized, and 1390 participants did not fulfil the eligibility criteria for this analysis (linked data available, no cataract within first 6 months), leaving 19 925 included. The median follow-up was 5 years. METHODS: Participants took 60 000 IU of vitamin D3 (n = 10 662) or placebo (n = 10 653) orally once per month for a maximum of 5 years. MAIN OUTCOME MEASURES: The primary outcome for this analysis was the first surgical treatment for cataract, ascertained through linkage to universal health insurance records and hospital data. RESULTS: Among 19 925 participants eligible for this analysis (mean age, 69.3 years; 46% women) 3668 participants (18.4%) underwent cataract surgery during follow-up (vitamin D: n = 1841 [18.5%]; placebo: n = 1827 [18.3%] ). The incidence of cataract surgery was similar between the two groups (incidence rate, 41.6 and 41.1 per 1000 person-years in the vitamin D and placebo groups, respectively; hazard ratio, 1.02; 95% confidence interval, 0.95-1.09). In prespecified subgroup analyses, the effect of vitamin D supplementation on the incidence of cataract surgery was not modified by age, sex, body mass index, predicted serum 25(OH)D concentration, or ambient ultraviolet radiation. CONCLUSIONS: Routinely supplementing older adults who live in an area with a low prevalence of vitamin D deficiency with high-dose vitamin D is unlikely to reduce the need for cataract surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients.

Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy. INTRODUCTION: Hypophosphatasia (HPP) is an inherited disorder associated with impaired primary mineralisation of osteoid (osteomalacia). HPP may be misdiagnosed as osteoporosis, a reduction in the volume of normally mineralized bone. Both illnesses may result in fragility fractures, although stress and atypical fractures are more common in HPP. Antiresorptive therapy, first-line treatment for osteoporosis, is relatively contraindicated in HPP. Misdiagnosis and mistreatment can be avoided by recognising a low serum alkaline phosphatase (ALP). Our aim was to determine the prevalence of a low ALP (< 30 IU/L) in patients attending an osteoporosis clinic, in a hospital-wide setting, and in a group of patients with atypical femoral fractures (AFF). METHODS: This was a retrospective study of patients attending an osteoporosis clinic at a tertiary hospital during 8 years (2012-2020). Patients were categorised into those with a transiently low ALP, those with low ALP on ≥ 2 occasions but not the majority of measurements, and those with a persistently low ALP. ALP levels were also assessed in hospital-wide records and a group of patients with AFF. RESULTS: Of 1839 patients attending an osteoporosis clinic, 168 (9%) had ≥ 1 low ALP, 50 (2.7%) had low ALP for ≥ 2 months, and seven (0.4%) had persistently low ALP levels. HPP was diagnosed in five patients, four of whom had persistently low ALP levels. The prevalence of HPP was 0.3% in the osteoporosis clinic and 3% in patients with ≥ 1 low ALP. Low ALP occurred in 0.6% of all hospital patients and 2/22 with AFF. CONCLUSION: Persistently low ALP in osteoporosis clinic attendees is easy to identify and signals the possibility of hypophosphatasia, a condition that may be mistaken for osteoporosis and incorrectly treated with antiresorptive therapy.

Effects of an 18-month community-based, multifaceted, exercise program on patient-reported outcomes in older adults at risk of fracture: secondary analysis of a randomised controlled trial.

This study identified that an 18-month community-based, multifaceted, exercise program consisting of resistance, weight-bearing impact, and balance/mobility training combined with osteoporosis education and behavioural support can improve health-related quality of life (HRQoL) and osteoporosis knowledge in older adults at risk of fracture, but only for those adherent to the exercise regime. PURPOSE: To evaluate the effects of an 18-month community-based exercise, osteoporosis education and behaviour change program (Osteo-cise: Strong Bones for Life) on HRQoL, osteoporosis knowledge and osteoporosis health beliefs. METHODS: This was a secondary analysis of an 18-month randomised controlled trial in which 162 older adults aged ≥ 60 years with osteopenia or increased falls/fracture risk were randomized to the Osteo-cise program (n = 81) or control group (n = 81). The program consisted of progressive resistance, weight-bearing impact and balance training (3 days/week); osteoporosis education to facilitate self-management of musculoskeletal health and behavioural support to enhance adherence to exercise. HRQoL, osteoporosis knowledge and osteoporosis health beliefs were assessed using the EuroQoL questionnaire (EQ-5D-3L), Osteoporosis Knowledge Assessment Tool and Osteoporosis Health Belief Scale, respectively. RESULTS: Overall, 148 participants (91%) completed the trial. Mean exercise adherence was 55% and mean attendance for the three osteoporosis educational sessions ranged from 63-82%. After 12 and 18 months, there were no significant effects of the Osteo-cise program on HRQoL, osteoporosis knowledge or health beliefs relative to controls. Per protocol analyses (≥ 66% exercise adherence; n = 41) revealed a significant net benefit in EQ-5D-3L utility for the Osteo-cise group relative to controls after 12 months (P = 0.024) and 18 months (P = 0.029) and a significant net improvement in osteoporosis knowledge scores at 18 months (P = 0.014). CONCLUSION: This study supports the importance of adherence to exercise regimes, as adherence to the Osteo-cise: Strong Bones for Life program was associated with improvements in HRQoL and osteoporosis knowledge in older adults at increased risk for falls and fractures. TRIAL REGISTRATION NUMBER: ACTRN12609000100291.

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.

The effect of vitamin D supplementation on pain: an analysis of data from the D-Health randomised controlled trial.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60-84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely 'some or more pain impact' and 'presence of any bodily pain') to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year), the mean (sd) 25(OH)D concentrations were 77 (sd 25) and 115 (sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration >50 nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (-0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D3/month had negligible effect on bodily pain.

Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.

PURPOSE: Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS: Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS: Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION: Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.

Effect of vitamin D supplementation on depression in older Australian adults.

OBJECTIVES: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. METHODS: We used data from the D-Health Trial (N = 21,315), a randomized double-blind placebo-controlled trial of monthly vitamin D3 for the prevention of all-cause mortality. Participants were Australians aged 60-84 years. Participants completed the Patient Health Questionnaire (PHQ-9) at 1, 2 and 5 years after randomization to measure depressive symptoms; national prescribing records were used to capture antidepressant use. We used mixed models and survival models. RESULTS: Analyses of PHQ-9 scores included 20,487 participants (mean age 69·3 years, 46% women); the mean difference (MD) in PHQ-9 score (vitamin D vs. placebo) was 0·02 (95% CI -0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ-9 score ≥10) (odds ratio 0·99; 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04; 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ-9 scores in those taking antidepressants at baseline (MD -0·25; 95% CI -0·49, -0·01; p-interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration <50 nmol/L (HR 0·88; 95% CI 0·75, 1·02; p-interaction = 0·01) and increased risk in those with predicted 25(OH)D ≥ 50 nmol/L (HR 1·10; 95% CI 1·01, 1·20). CONCLUSION: Monthly supplementation with high-dose vitamin D3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. CLINICAL TRIAL REGISTRATION: The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.

Disorganization and Musculoskeletal Diseases: Novel Insights into the Enigma of Unexplained Bone Abnormalities and Fragility Fractures.

PURPOSE OF REVIEW: Describe the potential contribution of disorganized tissue to the pathogenesis of bone abnormalities and fractures. Especially, fractures that are unexplained by bone loss (osteoporosis) or structural deterioration. RECENT FINDINGS: Currently, bone fragility is primarily viewed as due to loss, or decay (osteoporosis). However, it is also acknowledged that this view is limited because it does not explain many fractures or abnormalities such as necrosis, sclerosis, or infarcts. Atypical femoral fractures (AFFs) during antiresorptive therapy are an example. Hence, it is proposed that another distinct mechanism is responsible for bone diseases. A remarkable bone property distinct from mass and decay is the organization (arrangement) of its components. Components must be perfectly assembled or well-stacked to ensure "the right amount of bone, at the right place". Disorganization is an aberration that is conspicuous in many diseases, more so in conditions poorly associated with bone mass and decay such as osteogenesis imperfecta, hypophosphatasia, and AFFs. However, despite the likely critical role of disorganization, this feature has received limited clinical attention. This review focuses on the potential contribution of disorganization to bone in health and diseases. Particularly, we propose that disorganization, by causing ineffective transfer of loads, may produce not only bone abnormalities (pain, necrosis, infarct, sclerosis, delayed healing) but also fractures, especially AFFs or stress fractures. A disorganized element is one that is where it shouldn't be (improperly stacked elements). Hence, disorganization can be measured by quantifying the extent to which a tissue (pixel within an image) is at an incorrect location.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Vitamin D Supplementation and Antibiotic Use in Older Australian Adults: An Analysis of Data From the D-Health Trial.

BACKGROUND: Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection. METHODS: The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60-84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years. For this analysis, the primary outcome was the number of antibiotic prescription episodes; secondary outcomes were total number of prescriptions, repeat prescription episodes, and antibiotics for urinary tract infection. We estimated incidence rate ratios (IRRs) using negative binomial regression, and odds ratios using logistic regression. RESULTS: Vitamin D supplementation slightly reduced the number of prescription episodes (IRR, 0.98; 95% confidence interval [CI], .95-1.01), total prescriptions (IRR, 0.97; 95% CI, .93-1.00), and repeat prescription episodes (IRR, 0.96; 95% CI, .93-1.00). There was stronger evidence of benefit in people predicted to have insufficient vitamin D at baseline (prescription episodes IRR, 0.93; 95% CI, .87-.99). CONCLUSIONS: Vitamin D may reduce the number of antibiotic prescriptions, particularly in people with low vitamin D status. This supports the hypothesis that vitamin D has a clinically relevant effect on the immune system. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.

Challenges in the diagnosis and management of glucocorticoid-induced osteoporosis in younger and older adults.

OBJECTIVE: Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture-risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals. DESIGN: A narrative review is presented, following a systematic search of the literature from 2000 to 2021. RESULTS: Our current appreciation of glucocorticoid-induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood. CONCLUSION: Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.