Search

Summary: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.IntroductionThe aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).MethodsWe studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted & beta;-coefficients.ResultsA previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.ConclusionA previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitati

INTRODUCTION: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia's Home Medicine Review (HMR) can reduce patients' intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. METHOD AND ANALYSIS: Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants' cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. ETHICS AND DISSEMINATION: Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-r

BACKGROUND: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking. OBJECTIVE: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI. METHOD: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years. RESULTS: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p<0.05), respectively. CONCLUSION: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI

Patients with end-stage kidney disease (ESKD) have higher fracture rates and post-fracture mortality than the general population, but bone mineral density by dual energy X-ray absorptiometry (DXA) is less predictive of fracture in this population. Data from bone biopsy and high-resolution imaging indicate that patients on dialysis have reduced cortical thickness and increased cortical porosity, which contribute to fracture risk. The aim of this study was to assess cortical parameters using DXA in patients with ESKD. Using advanced hip analysis, normal age-related ranges were determined from 752 female and 861 male femur scans, and were compared to scans of 226 dialysis patients at time of transplantation. Female dialysis patients had lower cortical thickness (mm) at the femoral neck (2.59 +/- 1.42 vs. 5.23 +/- 1.85), calcar (3.46 +/- 1.07 vs. 5.09 +/- 1.30) and femoral shaft (4.42 +/- 1.21 vs. 7.44 +/- 2.07); p= 0.001 for each site. Buckling ratios (BR), higher values indicating greater femoral neck instability, were also higher for these women (8.21 +/- 4.6 vs. 3.63 +/- 1.42, P = 0.001). All findings were similar for men. Prevalent fracture was documented in 29% of dialysis patients, and in adjusted models, lower femoral neck cortical thickness and a higher BR were associated respectively with a 1.73 (1.22-2.46) and 1.82 (1.49-2.86) fold increased risk of prevalent vertebral fracture per standard deviation change. Cortical parameters measured by DXA are markedly abnormal in dialysis patients and are associated with prevalent vertebral fracture. These parameters should be assessed prospectively in patients with ESKD for utility in fracture prediction and targeting treatment.

BACKGROUND: It is unclear whether obesity and type 2 diabetes (T2D), either alone or in combination, induce left ventricular hypertrophy (LVH) independent of hypertension. In the current study, we provide clarity on this issue by rigorously analysing patient left ventricular (LV) structure via clinical indices and via LV geometric patterns (more commonly used in research settings). Importantly, our sample consisted of hypertensive patients that are routinely screened for LVH via echocardiography and normotensive patients that would normally be deemed low risk with no further action required. METHODS: This cross sectional study comprised a total of 353 Caucasian patients, grouped based on diagnosis of obesity, T2D and hypertension, with normotensive obese patients further separated based on metabolic health. Basic metabolic parameters were collected and LV structure and function were assessed via transthoracic echocardiography. Multivariable logistic and linear regression analyses were used to identify predictors of LVH and diastolic dysfunction. RESULTS: Metabolically healthy normotensive obese patients exhibited relatively low risk of LVH. However, normotensive metabolically non-healthy obese, T2D and obese/T2D patients all presented with reduced normal LV geometry that coincided with increased LV concentric remodelling. Furthermore, normotensive patients presenting with both obesity and T2D had a higher incidence of concentric hypertrophy and grade 3 diastolic dysfunction than normotensive patients with either condition alone, indicating an additive effect of obesity and T2D. Alarmingly these alterations were at a comparable prevalence to that observed in hypertensive patients. Interestingly, assessment of LVPWd, a traditional index of LVH, underestimated the presence of LV concentric remodelling. The implications for which were demonstrated by concentric remodelling and concentric hypertrophy strongly associating with grade 1 and 3 diastolic dysfunction respectiv

UNLABELLED: A 51 year old man presented with sepsis in the setting of thioamide-induced agranulocytosis. Empiric broad-spectrum antibiotics was followed by directed narrow-spectrum antibiotics, and his neutrophil count recovered with support from granulocyte-colony stimulating factor (G-CSF) analogue transfusions. After a brief period of multi-modal therapy for nine days including potassium iodide (Lugol's iodine), cholestyramine, propanolol and lithium to temper his persisting hyperthyroidism, a total thyroidectomy was performed while thyroid hormone levels remained at thyrotoxic levels. Postoperative recovery was uncomplicated and he was discharged home on thyroxine. There is limited available evidence to guide treatment in this unique cohort of patients who require prompt management to avert impending clinical deterioration. This case report summarises the successful emergent control of thyrotoxicosis in the setting of thioamide-induced agranulocytosis complicated by sepsis, and demonstrates the safe use of multi-modal pharmacological therapies in preparation for total thyroidectomy. LEARNING POINTS: Thioamide-induced agranulocytosis is an uncommon but potentially life-threatening complication of which all prescribers and patients need to be aware.A multi-modal preoperative pharmacological approach can be successful, even when thioamides are contraindicated, when needing to prepare a thyrotoxic patient for semi-urgent total thyroidectomy.There is not enough evidence to confidently predict the safe timing when considering total thyroidectomy in this patient cohort, and therefore it should be undertaken when attempts have first been made to safely reduce thyroid hormone levels.Thyroid storm is frequently cited as a potentially severe complication of thyroid surgery undertaken in thyrotoxic patients, although the evidence does not demonstrate this as a common occurrence.