Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures

Summary Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods /clinical perspective and updated literature search. Results The following areas are reviewed: categorisation of fracture risk; general pharmacological management of osteoporosis. Conclusions A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions

Are people following hip and knee arthroplasty at greater risk of experiencing a fall and fracture? Data from the Osteoarthritis Initiative

Introduction: Falls are a major challenge for older people and are a significant source of mortality and morbidity. There has been uncertainty as to whether people with total hip (THA) or knee (TKA) arthroplasty have a greater risk of falls and associated fractures. This analysis was to explore this question with a large community dataset. Materials and Methods: Data from all people enrolled onto the US Osteoarthritis Initiative programme who had undergone a THA (n=104) or TKA (n=165), within a 12 month period, were compared to those who had not undergone an arthroplasty (n=4631). Data was collected on: the number of participants who reported a fall within a 12 month period; the frequency of falls in this period; and whether a fracture was sustained during this period. Odd ratios were calculated for the probability of experiencing a fall or fracture between the groups. Results: There was no statistical difference in falls between people following THA (OR 0.90; 95% CI: 0.58 to 1.41) or TKA (OR: 0.95; 0.67 to 1.35) compared to a non-arthroplasty cohort. Whilst there was no statistical difference in fracture risk between people following TKA compared to non-arthroplasty individuals (OR: 1.25; 95% CI: 0.57 to 2.70), those who underwent THA had a 65% lower chance of experiencing a fracture in the initial 12 post-operative months compared to the non-THA cohort (OR 0.35; 95% CI: 0.19 to 0.65; p<0.01). Conclusions: There appears a lower chance of experiencing a fracture for people following THA compared to those who have not

Dupuytren’s disease predicts increased all-cause and cancer-specific mortality: analysis of a large cohort from the UK Clinical Practice Research Datalink

Objectives: Dupuytren’s disease (DD) is a common, chronic, fibroproliferative disease of the palmar fascia. The aetiology is unclear, but includes genetic predisposition alongside environmental factors. Several studies have suggested an association between DD and excess mortality. We aimed to evaluate this association in adult patients in the United Kingdom, and identify the causes of mortality. Methods: We used a large primary care database (Clinical Practice Research Datalink) linked to the Office of National Statistics to identify DD patients between 01/01/1995-31/12/2013. Each patient was matched by age, sex and GP practice to five DD-free controls. We used Cox regression models to study the association between DD and all-cause and cause-specific mortality, adjusting for confounders. Results: We identified 41965 DD patients and 209825 controls. All-cause mortality was increased in both unadjusted (HR 1.48, 99% CI 1.29-1.70, p<0.0001) and multivariable adjusted (HR 1.43, 1.25-1.65, p<0.0001) models in patients with DD, 12 years following diagnosis. Excess mortality was secondary to a wide range of causes, including cancer (HR 1.66,1.27-2.17, p<0.0001), an effect that persisted after adjustment for confounders. Conclusion: There is excess mortality associated with DD that can be partially explained through environmental factors. From time of diagnosis in primary care, there is a 12-year window of opportunity for intervention to reduce the impact of these factors. We observed an increased risk of cancer mortality independent of confounders, and hypothesise a shared genetic risk between DD and cancer

The challenges and opportunities of pharmacoepidemiology in bone diseases

Pharmacoepidemiology is used extensively in osteoporosis research and involves the study of the use and effects of drugs in large numbers of people. Randomized controlled trials are considered the gold standard in assessing treatment efficacy and safety. However, their results can have limited external validity when applied to day-to-day patients. Pharmacoepidemiological studies aim to assess the effect/s of treatments in actual practice conditions, but they are limited by the quality, completeness, and inherent bias due to confounding. Sources of information include prospectively collected (primary) as well as readily available routinely collected (secondary) (eg, electronic medical records, administrative/claims databases) data. Although the former enable the collection of ad hoc measurements, the latter provide a unique opportunity for the study of large representative populations and for the assessment of rare events at relatively low cost. Observational cohort and case-control studies, the most commonly implemented study designs in pharmacoepidemiology, each have their strengths and limitations. However, the choice of the study design depends on the research question that needs to be answered. Despite the many advantages of observational studies, they also have limitations. First, missing data is a common issue in routine data, frequently dealt with using multiple imputation. Second, confounding by indication arises because of the lack of randomization; multivariable regression and more specific techniques such as propensity scores (adjustment, matching, stratification, trimming, or weighting) are used to minimize such biases. In addition, immortal time bias (time period during which a subject is artefactually event-free by study design) and time-varying confounding (patient characteristics changing over time) are other types of biases usually accounted for using time-dependent modeling. Finally, residual "uncontrolled" confounding is difficult to assess, and hence to account for it, sensitivity analyses and specific methods (eg, instrumental variables) should be considered

Brief report: HIV infection is associated with worse bone material properties, independently of bone mineral density

Low bone mineral density (BMD) in HIV-infected individuals has been documented in an increasing number of studies. However, it is not clear whether it is the infection itself or the treatment that causes bone impairment. Microindentation measures bone material strength (Bone Material Strength index) directly. We recruited 85 patients, 50 infected with HIV and 35 controls. Median Bone Material Strength index was 84.5 (interquartile range 83-87) in HIV-infected patients and 90 (88.5-93) in controls (P < 0.001). No significant differences in BMD between cases and controls at any of the sites examined (total hip, femoral neck, and lumbar spine). HIV infection is associated with bone damage, independently of BMD

Clinical and genetic risk factors for acute incident venous Thromboembolism in ambulatory patients with COVID-19.

Importance: The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19-related VTE and relevant clinical and genetic risk factors remain to be elucidated. Objective: To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post-COVID-19 VTE. Design, Setting, and Participants: This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19-naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded. Exposures: First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia. Main Outcomes and Measures: The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models. Results: In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post-COVID-19 VTE. Conclusions and Relevance: In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19

Time Series Methods to Assess the Impact of Regulatory Action: A Study of UK Primary Care and Hospital Data on the Use of Fluoroquinolones

Purpose To illustrate the interest in using interrupted time series (ITS) methods, this study evaluated the impact of the UK MHRA's March 2019 Risk Minimisation Measures (RMM) on fluoroquinolone usage. Methods Monthly and quarterly fluoroquinolone use incidence rates from 2012 to 2022 were analysed across hospital care (Barts Health NHS Trust), primary care (Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD), and linked records from both settings (East Scotland). Rates were stratified by age (19–59 and ≥ 60 years old). Seasonality-adjusted segmented regression and ARIMA models were employed to model quarterly and monthly rates, respectively. Results Post-RMM, with segmented regression, both age groups in Barts Health experienced nearly complete reductions (> 99%); CPRD Aurum saw 20.19% (19–59) and 19.29% (  60) reductions; no significant changes in CPRD GOLD; East Scotland had 45.43% (19–59) and 41.47% (  60) decreases. Slope analysis indicated increases for East Scotland (19–59) and both CPRD Aurum groups, but a decrease for CPRD GOLD's  60; ARIMA detected significant step changes in CPRD GOLD not identified by segmented regression and noted a significant slope increase in Barts Health's 19–59 group. Both models showed no post-modelling autocorrelations across databases, yet Barts Health's residuals were non-normally distributed with non-constant variance. Conclusions Both segmented regression and ARIMA confirmed the reduction of fluoroquinolones use after RMM across four different UK primary care and hospital databases. Model diagnostics showed good performance in eliminating residual autocorrelation for both methods. However, diagnostics for hospital databases with low incident use revealed the presence of heteroscedasticity and non-normal white noise using both methods