751 research outputs found
Risk of fractures in patients with multiple sclerosis: a population-based cohort study.
Get PDFOBJECTIVE: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. METHODS: A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998-2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. RESULTS: During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls. CONCLUSIONS: Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics
Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database
No full textBACKGROUND: Two recent case-control studies by Meier et al. and van Staa et al. used the UK General Practice Research Database (GPRD) to examine the association between the use of statins and the risk of fractures, with different results. The objective of the present study was to examine methodological explanations for the discrepant results. METHODS: We created two datasets, which mimicked the previous study designs: a 'selected population' (SP) case-control dataset, with fracture cases matched to controls nested within a selected cohort (Meier et al.), and an 'entire population' (EP) case-control dataset, with both cases and controls sampled from the total GPRD population (van Staa et al.). Cases and controls were matched by gender, age (year of birth or 5 year age bands), and general practice. RESULTS: The study included 131 855 fracture cases. The crude odds ratio (OR) for hip fracture in statin users was 0.37 (95% CI 0.27-0.52) in the SP and 0.54 (95% CI 0.39-0.74) in the EP dataset. This difference was reduced when matching by year of birth, rather than by 5 year age bands: crude ORs were 0.58 (95% CI 0.43-0.79) and 0.61 (95% CI 0.44-0.88), respectively. In the SP dataset, 37% of the cases could be matched by year of birth, while this was achieved for 99% in the 'EP' dataset. The exposure time-window, the selection of confounders, and exclusion of high-risk patients also influenced results. CONCLUSION: Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered
Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy
No full textObjective: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). Methods: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1-year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials. Results: The study population comprised 306 patients with baseline and 1-year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1-point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06-3.21) and the daily GC dose (for each 10-mg dose increase, RR 1.62, 95% CI 1.11-2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57-12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present. Conclusion: The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture
The limitations of using simple definitions of glucocorticoid exposure to predict fracture risk: A cohort study
Get PDFPurpose To evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset. Methods Data from patients with rheumatoid arthritis (RA) were extracted from the Clinical Practice Research Datalink, a primary care database with electronic health records in the United Kingdom. Patients exposed to oral GCs were matched to up to two unexposed patients by age, gender and location. The first osteoporotic fracture was identified and adjusted and unadjusted cox proportional hazard ratios (HR) and 95% confidence intervals (CI) produced for fracture risk following GC therapy using different models of risk attribution. These include models demonstrating the effect of dose, duration and recency of GC exposure. Results There were 16,507 patients included. Exposed patients were older and had more comorbidities. GC therapy was associated with an increased risk of fracture, with the effect size influenced by risk attribution model. The risk of fracture decreased with less recent exposure from HR (95% CI) 1.66 (1.27, 2.16) during the first month of stopping GCs to 1.11 (0.79, 1.57) for between 1 and 3 months. The risk of fracture increased with current daily dose, HR 1.44 (1.17, 1.77) for 5–9.9 mg prednisolone equivalent dose (PEQ) to 3.02 (1.77, 5.15) for 15–19.9 mg PEQ. Risk of fracture increased with cumulative dose, a function of dose and duration, from HR 1.22 (1.03, 1.44) for <1 g to 1.83 (1.35, 2.48) for 7.5–10 g. Conclusion GC exposure was associated with excess fracture risk, with effect size differing according to definition of exposure. This highlights the need to incorporate all exposure dimensions (dose, duration and recency) in these patient's fracture risk assessments
Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study.
No full textBACKGROUND AND AIMS: Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not of non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database. METHODS: In a primary care-based nested case-control study, 231,778 patients with fracture and 231,778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index when known. RESULTS: AS was diagnosed in 758 subjects. The prevalence of AS was 0.18% in patients with fracture and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR 3.26; 95% CI 1.51 to 7.02). The risk of fractures of the forearm and hip was not significantly increased (OR 1.21; 95% CI 0.87 to 1.69 and OR 0.77; 95% CI 0.43 to 1.37, respectively). The risk of any clinical fracture was increased in patients with AS with a history of inflammatory bowel disease (OR 2.79; 95% CI 1.10 to 7.08), whereas it was decreased in patients with AS taking non-steroidal anti-inflammatory drugs (OR 0.65; 95% CI 0.50 to 0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine. CONCLUSIONS: Patients with AS have an increased risk of clinical vertebral fracture but not of non-vertebral fractures, while the risk of any clinical fracture is increased in patients with concomitant inflammatory bowel disease. The mechanism by which non-steroidal anti-inflammatory drugs reduce the risk of any clinical fracture warrants further research
Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids
No full textOBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses
Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates
No full textSummary: previous studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants.Introduction: previous studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects.Methods: a retrospective cohort study using the GPRD was conducted in patients aged 40 years and older starting proton pump inhibitors (PPI, N?=?234,144), H2 receptor antagonists (H2RA, N?=?166,798) or bisphosphonates (N?=?67,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression.Results: in the 6 months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H2RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10–1.20), hip (ARR 1.22, 95% CI 1.10–1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11–1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01–1.16) and hip fracture (ARR 1.24, 95% CI 1.08–1.42).Conclusions: ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigatio
Long acting beta2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: the general practice research database
No full textThe objective of this study was to describe risks of death and asthma outcomes with prescription of long-acting beta2-agonists (LABA), short-acting beta2-agonists (SABA) or inhaled corticosteroids (ICS) in general practice.The study population included beta2-agonist users aged 18+ in the UK General Practice Research Database linked to the national registry of hospitalisations. The study included 507,966 patients with 5.5 million SABA, 4.0 million ICS and 1.3 million LABA prescriptions. Rates of asthma outcomes increased with more severe treatment steps. The mortality rate was increased with least and most severe treatment steps. Higher relative rates (RR) of outcomes were found in recent starters and heavy long-term users with LABA, SABA and ICS. The RRs in heavy long-term users were 1.9 for all-cause mortality and 3.0 for asthma death with SABA, 1.4 and 1.6 with LABA and 1.7 and 2.2 with ICS. The RR of death was statistically similar over time between LABA and ICS despite changes in exposure.Risks for death and asthma outcomes varied substantially with exposure characteristics. The statistical power for detecting increases in asthma death was low. The results of this study did not indicate that LABA exposure was associated with an increased risk for all-cause mortality.<br/
Children and the risk of fractures caused by oral corticosteroids
No full textOral corticosteroids are known to increase the risk of fracture in adults, but their effects in children remain uncertain. The medical records of general practitioners in the United Kingdom (from the General Practice Research Database) were used to estimate the incidence rates of fracture of children ages 4-17 years taking oral corticosteroids (n = 37,562) and of control children taking nonsystemic corticosteroids (n = 345,748). Each child with a fracture (n = 22,846) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. The average duration of treatment was 6.4 days (median, 5 days). The risk of fracture was increased in children with a history of frequent use of oral corticosteroids; children who received four or more courses of oral corticosteroids had an adjusted odds ratio (OR) for fracture of 1.32 (95% CI, 1.03-1.69). Of the various fracture types, the risk of humerus fracture was doubled in children who received four or more courses of oral corticosteroids (adjusted OR, 2.17 [1.01-4.67]). Fracture risk was also increased among children using 30 mg prednisolone or more each day (adjusted OR for fracture, 1.24 [1.00-1.52]) and among those receiving four or more courses of oral corticosteroids (OR, 1.32 [1.03-1.69]). Children who stopped taking oral corticosteroids had a comparable risk of fracture to those in the control group. Our findings suggest that children who require more than four courses of oral corticosteroid as treatment for underlying disease are at increased risk of fracture. It is not entirely clear whether this relates directly to oral corticosteroid use or the underlying disease and its severity. Irrespective of these issues, this group of children is at increased risk of fracture
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