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Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands.

ABSTRACT: Data from in vivo studies have indicated a role for beta-blockers in the prevention of bone loss. Some epidemiological studies have found protective effects of beta-blockers on fracture risk. However, there is limited information on the association with cumulative dose and type of beta-blockers used. We conducted two case-control studies using data from the UK General Practice Research Database (GPRD) and the Dutch PHARMO Record Linkage System (RLS). Cases were patients with a first hip or femur fracture; controls were individually matched on practice/region, gender, year of birth, and calendar time. Current use of beta-blockers was defined as a prescription in 90 days before the index date. We adjusted for medical conditions and drugs associated with falling or bone mineral density. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression analysis. The study population included 22,247 cases and controls in the GPRD and 6,763 cases and 26,341 controls in the PHARMO RLS. Current use of beta-blockers was associated with a reduced risk of hip/femur fracture in both the GPRD (adjusted OR = 0.82, 95% CI 0.74-0.91) and PHARMO RLS (adjusted OR = 0.87, 95% CI 0.80-0.95) study populations. However, this reduction of risk was not associated with cumulative dose, lipophilicity, or receptor selectivity of beta-blockers. The protective effect of beta-blockers was only present among patients with a history of use of other antihypertensive agents (GPRD adjusted OR = 0.72, 95% CI 0.64-0.83; PHARMO RLS adjusted OR = 0.76, 95% CI 0.67-0.86) but not in patients using beta-blockers only (GPRD adjusted OR = 0.97, 95% CI 0.82-1.14; PHARMO RLS adjusted OR = 1.01, 95% CI 0.90-1.14). Also, in patients with a history of use of other antihypertensive agents, no dose-response relationship with beta-blocker use was found. The effect was constant with cumulative dose and the OR was below 1.0 even among patients who just started treatment with beta-blockers. As the mechanism by which beta-blockers could influence bone mineral density is likely to need some time to exert a clinically relevant effect, all these finding suggests that the association between beta-blockers and fracture risk is not causal.

SUBMITTER: de Vries F

PROVIDER: S-EPMC1914229 | biostudies-other | 2007 Feb

REPOSITORIES: biostudies-other

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Project description:Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

Project description:BackgroundHealth economic evaluations rely on the accurate measurement of health service resource use in order to calculate costs. These are usually measured with patient completed questionnaires using instruments such as the Client Service Receipt Inventory (CSRI). These rely on participants' recall and can be burdensome to complete. Health service activity data are routinely captured by electronic databases.The aim was to test methods for obtaining these data and compare with those data collected using the CSRI, within a feasibility study of an enhanced rehabilitation intervention following hip fracture (Fracture in the Elderly Multidisciplinary Rehabilitation: FEMuR).MethodsPrimary care activity including prescribing data was obtained from the Secure Anonymised Information Linkage (SAIL) Databank and secondary care activity (Emergency Department attendances, out-patient visits and in-patient days) directly from Betsi Cadwaladr University Health Board (BCUHB), North Wales, UK. These data were compared with patient responses from the CSRI using descriptive statistics and the intraclass correlation coefficient (ICC).ResultsIt was possible to compare health service resource use data for 49 out of 61 participants in the FEMuR study. For emergency department (ED) attendances, records matched in 23 (47%) cases, 21 (43%) over-reported on electronic records compared with CSRI and five participants (10%) under-reported, with an overall ICC of 0.42. For out-patient episodes, records matched in only six cases, 28 participants over-reported on electronic records compared with CSRI and 15 (12%) under-reported, with an overall ICC of only 0.27. For in-patient days, records matched exactly in only five cases (10%), but if an error margin of 7 days was allowed, then agreement rose to 39 (66%) cases, and the overall ICC for all data was 0.88.It was only possible to compare prescribing data for 12 participants. For prescribing data, the SAIL data reported 117 out of 118 items (99%) and the CSRI only 89 (79%) items.ConclusionsThe use of routinely collected data has the potential to improve the efficiency of trials and other studies. Although the methodology to make the data available has been demonstrated, the data obtained was incomplete and the validity of using this method remains to be demonstrated.Trial registrationTrial registration: ISRCTN22464643 Registered 21 July 2014.

Project description:ImportanceOral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.ObjectiveTo investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects.Design, setting, and participantsRetrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014.ExposuresAlendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation.Main outcomes and measuresThe primary outcome was incident hip fracture.ResultsOf the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group.Conclusions and relevanceAmong older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

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Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands.

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