A Sami

Bio: A Sami is an academic researcher from University of Oxford. The author has contributed to research in topics: Osteoporosis & Population. The author has an hindex of 2, co-authored 2 publications receiving 21 citations.

A patient-level key performance indicator set to measure the effectiveness of fracture liaison services and guide quality improvement: a position paper of the IOF Capture the Fracture Working Group, National Osteoporosis Foundation and Fragility Fracture Network

Abstract: The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement. Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level. The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs. Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the 80% levels except for treatment recommendation where a level of 50% was used. This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.

Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR alliance

Abstract: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). Participants: the database source populations were included for population-based analyses, and SR users for patient-level analyses. Intervention: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4–62.9) in the reference to 8.5 (8.5–8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4–7.4) to 0.2 (0.2–0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database

Abstract: The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting.This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed.A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk.This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

Anti‐osteoporosis medication dispensing by clinical commissioning groups in England – an ecological study of variability in practice and of the effect of the Covid‐19 pandemic

Abstract: To investigate whether the rate of Anti‐Osteoporosis Medication (AOM) dispensing was related to prevalence of risk factors and hip fracture incidence in the local population.

Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development

Abstract: CDATA[Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents, such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services.

Abstract: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

The role of the Fracture Liaison Service (FLS) in subsequent fracture prevention in the extreme elderly.

Abstract: Several guidelines recommend a bone and fall-related osteoporosis risk assessment in all patients with fracture and age > 50 years. In practice, however, there is no consensus whether screening > 85 years is useful. To evaluate the subsequent fracture risk in all patient > 85 years, comparing the two populations of Fracture Liaison Service (FLS) attenders and non-attenders. All patients > 85 years that presented at the FLS with a non-vertebral fracture were included in the study during a 5-year period (September 2004 and December 2009). Excluded were pathologic fractures, death 85 years seems to be limited. In practice a large proportion of these patients are not screened.

Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK

Abstract: The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94–1.18) and 0.96 (0.78–1.18)], strontium [0.90 (0.61–1.34) and 1.19 (0.82–1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25–12.66)] and teriparatide [1.27 (0.59–2.71)] in Spain, did not differ versus alendronate. Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy). Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000–2014 (CPRD) or 2001–2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used. Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94–1.18) and 0.96 (0.78–1.18) for other bisphosphonates, and 0.90 (0.61–1.34) and 1.19 (0.82–1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25–12.66) for denosumab and 1.27 (0.59–2.71) for teriparatide in BIFAP. VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.