Abstract Summary Rates of fracture worldwide are changing. Using the Clinical Practice Research Datalink (CPRD), age, and gender, geographical, ethnic and socioeconomic trends in fracture rates ...across the United Kingdom were studied over a 24-year period 1988–2012. Previously observed patterns in fracture incidence by age and fracture site were evident. New data on the influence of geographic location, ethnic group and socioeconomic status were obtained. Introduction With secular changes in age- and sex-specific fracture incidence observed in many populations, and global shifts towards an elderly demography, it is vital for health care planners to have an accurate understanding of fracture incidence nationally. We aimed to present up to date fracture incidence data in the UK, stratified by age, sex, geographic location, ethnicity and socioeconomic status. Methods The Clinical Practice Research Datalink (CPRD) contains anonymised electronic health records for approximately 6.9% of the UK population. Information comes from General Practitioners, and covers 11.3 million people from 674 practices across the UK, demonstrated to be representative of the national population. The study population consisted of all permanently registered individuals aged ≥ 18 years. Validated data on fracture incidence were obtained from their medical records, as was information on socioeconomic deprivation, ethnicity and geographic location. Age and sex-specific fracture incidence rates were calculated. Results Fracture incidence rates by age and sex were comparable to those documented in previous studies and demonstrated a bimodal distribution. Substantial geographic heterogeneity in age and sex adjusted fracture incidence was observed, with rates in Scotland almost 50% greater than those in London and South East England. Lowest rates of fracture were observed in black individuals of both sexes; rates of fragility fracture in white women were 4.7 times greater than in black women. Strong associations between deprivation and fracture risk were observed in hip fracture in men, with a relative risk of 1.3 (95% CI 1.21–1.41) in Index of Multiple Deprivation category 5 (representing the most deprived) compared to category 1. Conclusions This study presents robust estimates of fracture incidence across the UK, which will aid decisions regarding allocation of healthcare provision to populations of greatest need. It will also assist the implementation and design of strategies to reduce fracture incidence and its personal and financial impact on individuals and health services.
Osteoporotic fragility fractures, that are common in men and women, signal increased risk of future fractures and of premature mortality. Less than one-third of postmenopausal women and fewer men are ...prescribed active treatments to reduce fracture risk. Therefore, in this study the association of oral bisphosphonate recommendation with subsequent fracture and mortality over eight years in a fracture liaison service setting was analysed.
In this prospective cohort study, 5011 men and women aged >50 years, who sustained a clinical fracture, accepted the invitation to attend the fracture liaison service of the West Glasgow health service between 1999 and 2007. These patients were fully assessed and all were recommended calcium and vitamin D. Based on pre-defined fracture risk criteria, 2534 (50.7%) patients were additionally also recommended oral bisphosphonates. Mortality and subsequent fracture risk were the pre-defined outcomes analysed using Cox proportional hazard models.
Those recommended bisphosphonates were more often female (82.9 vs. 72.4%), were older (73.4 vs. 64.4 years), had lower bone mineral density T-score (-3.1 vs. -1.5) and more had sustained hip fractures (21.7 vs. 6.2%; p < 0.001). After adjustments, patients recommended bisphosphonates had lower subsequent fracture risk (Hazard Ratio (HR): 0.60; 95% confidence interval (CI): 0.49-0.73) and lower mortality risk (HR: 0.79, 95%CI: 0.64-0.97).
Of the patients, who are fully assessed after a fracture at the fracture liaison service, those with higher fracture risk and a recommendation for bisphosphonates had worse baseline characteristics. However, after adjusting for these differences, those recommended bisphosphonate treatment had a substantially lower risk for subsequent fragility fracture and lower risk for mortality. These community-based data indicate the adverse public health outcomes and mortality impacts of the current low treatment levels post fracture could be improved by bisphosphonate recommendation for both subsequent fracture and mortality.
Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs ...(AOD).
We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py).
In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 2.3 to 169.7 per 10,000py), followed by a plateau and a 12% decrease in the last three years. In men, a less steep increase from 1990 to 2007 (from 1.4 to 45.3 per 10,000py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85–89years (248.9 per 10,000py in women and 119.3 in men). There were marked differences between ethnic groups and regions. Bisphosphonates were the most frequently prescribed AODs: etidronate till 2000, and then subsequently alendronate.
We have demonstrated marked secular changes in rates of anti-osteoporosis drug prescription over the last two decades. The plateau (and decrease amongst women) in rates in recent years, set against an ever ageing population, is worrying, suggesting that the well-documented care gap in osteoporosis treatment persists. The differences in prescription rates by geographic location and ethnicity raise intriguing questions in relation to underlying fracture rates, provision of care and health behaviour.
We studied the prescription incidence of anti-osteoporosis drugs (AOD) from 1990 to 2012 in the UK CPRD. Overall AOD prescription incidence showed a strong increase from 1990 to 2006, followed by a plateau in both sexes and a decrease amongst women in the last three years.
•In UK CPRD we documented rates of anti-osteoporosis treatment by age, sex, ethnicity, geographic location and calendar time.•In women, annual rates of first prescription increased from 1990-2006 followed by a plateau and a 12% decrease 2009-2012.•In men, prescription rates increased less steeply from 1990-2007 and then levelled from 2008 onwards.•There were marked differences in anti-osteoporosis treatment rates by ethnicity and geographic location within the UK.
Summary
We studied sex-specific incidence rates in a population 50 years or older in the UK. In the period of 1990–2012, the overall rate of fracture did not change, but there were marked secular ...alterations in the rates of individual fracture types, particularly hip and spine fractures in the elderly.
Introduction
There is increasing evidence of secular changes in age- and sex- adjusted fracture incidence globally. Such observations broadly suggest decreasing rates in developed countries and increasing rates in transitioning populations. Since altered fracture rates have major implications for healthcare provision and planning, we investigated secular changes to age- and sex-adjusted fracture risk amongst the UK population aged 50 years or above from 1990 till 2012.
Methods
We undertook a retrospective observational study using the Clinical Practice Research Datalink (CPRD), which contains the health records of 6.9 % of the UK population. Site-specific fracture incidence was calculated by calendar year for men and women separately, with fracture type categorised according to ICD-9 classification. Linear regression analysis was used to calculate mean annualised change in absolute incidence. For presentational purposes, mean rates in the first 5 years and last 5 years of the period were calculated.
Results
Overall fracture incidence was unchanged in both women and men from 1990 to 2012. The incidence of hip fracture remained stable amongst women (1990–1994 33.8 per 10,000 py; 2008–2012 33.5 per 10,000 py;
p
trend annualised change in incidence = 0.80) but rose in men across the same period (10.8 to 13.4 per 10,000 py;
p
= 0.002). Clinical vertebral fractures became more common in women (8.9 to 11.8 per 10,000 py;
p
= 0.005) but remained comparable in men (4.6 to 5.9 per 10,000 py;
p
= 0.72). Similarly, the frequency of radius/ulna fractures did not change in men (9.6 to 9.6 per 10,000 py;
p
= 0.25), but, in contrast, became less frequent in women (50.4 to 41.2 per 10,000 py;
p
= 0.001). Secular trends amongst fractures of the carpus, scapula, humerus, foot, pelvis, skull, clavicle, ankle, patella, and ribs varied according to fracture site and sex.
Conclusion
Although overall sex-specific fracture incidence in the UK population 50 years or over appears to have remained stable over the last two decades, there have been noticeable changes in rates of individual fracture types. Given that the impact of a fracture on morbidity, mortality, and health economy varies according to fracture site, these data inform the provision of healthcare services in the UK and elsewhere.
At presentation with a fracture, 26.5% of evaluated patients have previously unknown contributors to secondary osteoporosis and metabolic bone diseases and 63.9% vitamin D deficiency.
Background:
...Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown.
Methods:
All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50–97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T4, serum and urine protein electrophoresis, and in men also serum testosterone).
Results:
Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density.
Conclusion:
At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present.
Summary
Vertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of ...VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs.
Introduction
Vertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7–T8 and T11–T12 (“cVFs”) and less commonly at T4–T6 and T9–T10 (“lcVF”). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs.
Methods
Chest CT images of T4–T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex).
Results
On vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (
p
< 0.0001), 25% lower in subjects with lcVFs (
p
< 0.0001) and lowest in subjects with cVFs and lcVFs (− 32%,
p
< 0.0001). The highest ORs for presence of VFs per − 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6).
Conclusions
The association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution.
Trial registration
Clinicaltrials.gov
identifier: NCT00292552
Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are ...clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting.
In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting.
The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs.
Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.
•Of 103,871 ICU patients, 38% are exposed to a clinically relevant potential drug-drug interaction.•The most frequent interactions involve QT-prolonging agents, digoxin or NSAIDs.•Tailoring computerized decision support systems to the ICU may improve medication safety by reducing alert fatigue.
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
Summary
In this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent ...treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures.
Introduction
Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population.
Methods
A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids.
Results
Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified.
Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06–2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77–0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20–1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07–2.02).
Conclusions
Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk.
Background
Long‐term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic ...antiseizure drugs is limited. Therefore, the aim of this cross‐sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID).
Methods
A dual‐energy X‐ray absorptiometry of lumbar spine (L1–L4) and hip was performed in 24 children, residing in a long‐stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25‐hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files.
Results
Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z‐score > − 2.0). Of the 16 children with a low BMD (Z‐score ≤ − 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin‐corrected calcium (2.28–2.50 mmol/L) and (supplemented) vitamin D (16–137 nmol/L) were within the normal range.
Conclusions
This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.
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