RESUMO
BACKGROUND: The use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been linked to adverse effects on bone health, but findings are conflicting. This study aimed to quantify the associations between newer antidepressants and bone mineral density (BMD) and fracture risk through a comprehensive meta-analysis. METHODS: Observational studies on the association between the use of novel antidepressants and BMD and hip fracture were systematically searched in PubMed, Embase, CINAHL, Cochrane Library, and Scopus. Random effects meta-analyses were conducted to pool results across the eligible studies. The heterogeneity, publication bias, and influence were assessed extensively. RESULTS: 14 eligible studies with 1,417,134 participants were identified. Antidepressant use was associated with significantly lower BMD compared to non-use at all skeletal sites examined, with pooled standardized mean differences (SMD) ranging from -0.02 (total hip) to -0.04 (femoral neck). Importantly, antidepressant use was associated with a 2.5-fold increased risk of hip fracture (pooled odds ratio (OR) 2.50, 95% CI 2.26-2.76). While heterogeneity was detected, the overall findings were robust in sensitivity analyses. CONCLUSIONS: This meta-analysis provided strong evidence that novel antidepressants, especially widely used SSRIs, have detrimental impacts on bone health. The observed associations with decreased BMD and doubled hip fracture risk have important clinical implications.
Assuntos
Antidepressivos , Densidade Óssea , Fraturas do Quadril , Osteoporose , Humanos , Densidade Óssea/efeitos dos fármacos , Antidepressivos/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Fatores de RiscoRESUMO
This Viewpoint discusses the ongoing lawsuit between plaintiffs who had been affected by atypical femoral fractures while receiving alendronate and the drug manufacturer.
Assuntos
Alendronato , Conservadores da Densidade Óssea , Rotulagem de Medicamentos , Fraturas Ósseas , Fraturas do Quadril , Humanos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/prevenção & controle , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normas , Alendronato/efeitos adversos , Alendronato/farmacologia , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/fisiopatologia , Remodelação Óssea/efeitos dos fármacos , Fraturas Espontâneas/induzido quimicamente , Fraturas Espontâneas/fisiopatologia , Aprovação de Drogas/legislação & jurisprudência , Rotulagem de Medicamentos/legislação & jurisprudência , Rotulagem de Medicamentos/normasRESUMO
BACKGROUND: To enhance postoperative patient survival, particularly in older adults, understanding the predictors of mortality following hip fracture becomes paramount. Air pollution, a prominent global environmental issue, has been linked to heightened morbidity and mortality across a spectrum of diseases. Nevertheless, the precise impact of air pollution on hip fracture outcomes remains elusive. OBJECTIVE: This retrospective study aims to comprehensively investigate the profound influence of a decade-long exposure to 12 diverse air pollutants on the risk of post-hip fracture mortality among older Taiwanese patients (older than 60 years). We hypothesized that enduring long-term exposure to air pollution would significantly elevate the 1-year mortality rate following hip fracture surgery. METHODS: From Taiwan's National Health Insurance Research Database, we obtained the data of patients who underwent hip fracture surgery between July 1, 2003, and December 31, 2013. Using patients' insurance registration data, we estimated their cumulative exposure levels to sulfur dioxide (SO2), carbon dioxide (CO2), carbon monoxide (CO), ozone (O3), particulate matter having a size of <10 µm (PM10), particulate matter having a size of <2.5 µm (PM2.5), nitrogen oxides (NOX), nitrogen monoxide (NO), nitrogen dioxide (NO2), total hydrocarbons (THC), nonmethane hydrocarbons (NMHC), and methane (CH4). We quantified the dose-response relationship between these air pollutants and the risk of mortality by calculating hazard ratios associated with a 1 SD increase in exposure levels over a decade. RESULTS: Long-term exposure to SO2, CO, PM10, PM2.5, NOX, NO, NO2, THC, NMHC, and CH4 demonstrated significant associations with heightened all-cause mortality risk within 1 year post hip fracture surgery among older adults. For older adults, each 1 SD increment in the average exposure levels of SO2, CO, PM10, PM2.5, NOX, NO, NO2, THC, NMHC, and CH4 corresponded to a substantial escalation in mortality risk, with increments of 14%, 49%, 18%, 12%, 41%, 33%, 38%, 20%, 9%, and 26%, respectively. We further noted a 35% reduction in the hazard ratio for O3 exposure suggesting a potential protective effect, along with a trend of potentially protective effects of CO2. CONCLUSIONS: This comprehensive nationwide retrospective study, grounded in a population-based approach, demonstrated that long-term exposure to specific air pollutants significantly increased the risk of all-cause mortality within 1 year after hip fracture surgery in older Taiwanese adults. A reduction in the levels of SO2, CO, PM10, PM2.5, NOX, NO, NO2, THC, NMHC, and CH4 may reduce the risk of mortality after hip fracture surgery. This study provides robust evidence and highlights the substantial impact of air pollution on the outcomes of hip fractures.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Fraturas do Quadril , Humanos , Idoso , Estudos de Coortes , Dióxido de Nitrogênio/análise , Estudos Retrospectivos , Taiwan/epidemiologia , Dióxido de Carbono , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Fraturas do Quadril/cirurgia , Fraturas do Quadril/induzido quimicamente , Óxido Nítrico , HidrocarbonetosRESUMO
PURPOSE: Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90 days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC (≥ 70 mg prednisolone or equivalent; PSL) in the initial 90 days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080 days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90 days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC ≥ 5 mg PSL/day had a significantly increased fracture risk in the stratum of 30-59 days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5 mg PSL/day) for 90 days in the initial 90 days of GC therapy had a significantly increased fracture risk. CONCLUSIONS: GC exposure in the initial 90 days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90 days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.
Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Masculino , Humanos , Feminino , Idoso , Glucocorticoides/efeitos adversos , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos Retrospectivos , Japão/epidemiologia , Seguro Saúde , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: Many studies have reported conflicting results for the use of tramadol with the risk of fractures, especially hip fractures. This systematic review and meta-analysis study aimed to evaluate the association of tramadol use versus codeine use with the risk of hip fracture for the first time. METHODS: PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find studies that examined the association of tramadol use with hip fracture risk in patients with osteoarthritis up to May 2023. The risk of hip fracture secondary to tramadol versus codeine use was estimated based on age and sex. This systematic review was conducted based on the PRISMA checklist. Heterogeneity between studies was evaluated using Cochran's Q and I2 tests. Egger's test was used to check publication bias. The Newcastle-Ottawa Checklist (NOS) was used to assess the quality of the studies. FINDINGS: Ten studies with 1,939,293 participants were reviewed. The majority of participants were female. Based on the study evaluation checklist, most studies were of good quality. Tramadol use significantly increases the overall risk of hip fracture. (HR: 1.32, 95% CI: 1.14, 1.51, P: 0.001, I2:19.3%) Tramadol use significantly increases the risk of hip fracture in men (HR: 1.48, 95% CI: 1.24, 1.73, P: 0.001 I2:35%) and age ≤65 years (HR: 1.63, 95% CI: 1.45, 1.80, P: 0.001, I2:0%). CONCLUSION: The use of tramadol significantly increases the risk of hip fracture. This increased risk of hip fracture was greater in males younger than 65 years.
Assuntos
Fraturas do Quadril , Osteoartrite , Tramadol , Humanos , Codeína , Fraturas do Quadril/induzido quimicamente , Osteoartrite/tratamento farmacológico , Tramadol/efeitos adversos , Estudos Observacionais como AssuntoRESUMO
Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904-0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628-0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures.
Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Humanos , Vitamina D/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Incidência , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/induzido quimicamente , Vitaminas/uso terapêutico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Fraturas do Quadril/induzido quimicamenteRESUMO
BACKGROUND: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING: French Ministry of Health, HiFIT trial.
Assuntos
Anemia , Fraturas do Quadril , Ácido Tranexâmico , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ácido Tranexâmico/uso terapêutico , Ácido Tranexâmico/efeitos adversos , Fraturas do Quadril/cirurgia , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/tratamento farmacológico , Transfusão de Sangue , Ferro/uso terapêutico , Anemia/tratamento farmacológico , Anemia/etiologia , Hemoglobinas , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of anti- diabetic drugs on fractures. But so far, no meta-analysis study has been conducted to investigate the effect of diabetic drugs on hip fractures. Therefore, this study investigated the relationship between anti-diabetic drugs (Metformin, Sulfonylurea, and insulin) with hip fractures. METHODS: In this systematic review and meta analysis study, PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find relevant studies. Two researchers included related studies after screening based on the title and full text. Cochran's Q and I2 tests were used to assess heterogeneity between studies. Publication bias between studies was evaluated for each drug using Egger's test. A 95% confidence interval was used for effect size significance. Overall, 49 studies, including 6,631,297 participants, were reviewed. RESULTS: The results showed that metformin significantly reduced the risk of hip fracture (HR: 0.833, 95% CI: 0.759, 0.914, P:0.001). Consumption of sulfonylurea compounds was significantly associated with an increased risk of hip fracture. (HR: 1.175, 95% CI:1.068,1.293, P:0.001), The risk of hip fracture in patients receiving insulin was significantly higher than in diabetic patients who did not receive insulin. (HR:1.366, 95% CI:1.226,1.522, P:0.001). CONCLUSION: The results of this study showed that taking metformin reduces the risk of hip fracture, and insulin and Sulfonylurea increase the risk of hip fracture.
Assuntos
Diabetes Mellitus , Fraturas do Quadril , Metformina , Idoso , Humanos , Insulina/efeitos adversos , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Bases de Dados Factuais , Metformina/efeitos adversos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologiaRESUMO
AIM: Some clinical trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with fracture risk. However, this notion remains controversial. This study aimed to evaluate hip fracture risk after the use of SGLT2 inhibitors while controlling for factors that may affect fracture risk. Furthermore, hip fracture risk is evaluated in relation to the SGLT2 inhibitors component and its concomitant use with other antidiabetic agents. METHODS: Using large-scale real-world data, this case-control study investigated hospitalized patients between January 2018 and December 2020. Patients were aged 65-89 years and had been prescribed with SGLT2 inhibitors at least twice. Patients with hip fracture (cases) and those without (controls) were identified via 1:3 matching according to sex, age (±3 years), hospital size classification, and number of concomitant antidiabetic agents. Exposure to SGLT2 inhibitors of the cases and controls was compared with the use of multivariate conditional logistic regression. RESULTS: After matching, 396 cases and 1081 controls were identified. The adjusted odds ratio for patients receiving treatment with SGLT2 inhibitors was 0.83 (95% confidence interval: 0.55-1.26), indicating no increase in hip fracture risk. Additionally, no increased risk was observed with respect to SGLT2 inhibitors by component or concomitant use with other antidiabetic agents. CONCLUSION: Our study showed that SGLT2 inhibitors do not increase hip fractures in older patients. However, because the risk assessment of SGLT2 inhibitors by component and their concomitant use with other antidiabetic agents is based on a limited number of patients, it is important to interpret the results with caution. Geriatr Gerontol Int 2023; 23: 418-425.
Assuntos
Diabetes Mellitus Tipo 2 , Fraturas do Quadril , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Casos e Controles , Japão/epidemiologia , Hipoglicemiantes/efeitos adversos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/induzido quimicamente , Glucose , SódioRESUMO
By using propensity-score matched cohorts, we compared the risk of incident hip fracture between melatonin initiators and hypnotic benzodiazepines initiators. The initiation of melatonin was not associated with an increased risk of hip fracture. INTRODUCTION: Melatonin is hypothesized to suppress bone loss, but a previous study reported an increased risk of hip fracture among melatonin users compared with non-users, which was however susceptible to confounding by indication. This study aimed to compare the risk of hip fracture between melatonin initiators and initiators of its active comparators, i.e., hypnotic benzodiazepines. METHODS: Among individuals aged 40 years or older without a history of hip fracture or cancer in the IQVIA Medical Research Database (IMRD) in the UK (2000-2018), a propensity score-matched cohort study was conducted to examine the association of melatonin initiation vs. hypnotic benzodiazepines initiation with the risk of hip fracture. RESULTS: After propensity score matching, 9,038 patients were included (4,519 melatonin initiators and 4,519 hypnotic benzodiazepines initiators). During the entire follow-up, 41 cases of hip fracture occurred in the melatonin cohort, and 51 cases occurred in the hypnotic benzodiazepines cohort. The absolute rate difference in hip fracture between melatonin initiators and hypnotic benzodiazepines initiators was -0.8 (95% CI: -1.9 to 0.3) per 1000 person-years and the multivariable-adjusted hazard ratio (HR) of hip fracture for melatonin initiators was 0.78 (95% CI: 0.51 to 1.17). CONCLUSION: In this population-based cohort study, the risk of hip fracture among melatonin initiators was not higher, if not lower, than that among hypnotic benzodiazepines initiators.
Assuntos
Fraturas do Quadril , Melatonina , Humanos , Benzodiazepinas/efeitos adversos , Estudos de Coortes , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Melatonina/efeitos adversos , AdultoRESUMO
BACKGROUND AND OBJECTIVE: The use of benzodiazepines and nonbenzodiazepines increases the risk for hip fracture, but the effect of suvorexant, an orexin receptor antagonist, is not clear. The objective of this study was to investigate the association between suvorexant use and hip fractures in older adults. METHODS: A case-control study was conducted using real-world data (RWD) from Medical Data Vision Co., Ltd. with patients hospitalized between January 2019 and December 2020. Patients were aged 65-84 years and had been prescribed suvorexant at least once. Patients with hip fracture (cases) and those without (controls) were identified by matching up to 1:4 for sex, age (± 2 years), and hospital size category. Suvorexant exposure was identified the day before hospitalization. Hip fracture risk associated with suvorexant was presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI) using conditional logistic regression analysis. RESULTS: Matching identified 389 cases and 1509 controls. The risk of hip fracture was not increased in patients treated with suvorexant [aOR: 0.86, 95% confidence interval (CI) 0.61-1.20]. Additionally, concomitant use of suvorexant with other hypnotics did not increase the risk. Benzodiazepines (1.01, 0.46-2.22), nonbenzodiazepines (1.16, 0.57-2.34), and melatonin (1.80, 0.82-3.94) were combined with suvorexant. The risk was increased for the use of benzodiazepine without suvorexant (1.88, 1.10-3.21). CONCLUSIONS: Using RWD in Japanese older adults, we showed that sleep therapy with suvorexant was not associated with an increased risk of hip fracture. The results provide evidence-based drug safety information for the selection of hypnotics for sleep disorders, which increase with age.
Assuntos
Fraturas do Quadril , Humanos , Idoso , Estudos de Casos e Controles , Japão/epidemiologia , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Benzodiazepinas/efeitos adversosRESUMO
INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.
Assuntos
Demência , Inibidores da Dipeptidil Peptidase IV , Fraturas do Quadril , Fraturas da Coluna Vertebral , Idoso , Humanos , Hipoglicemiantes/efeitos adversos , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/induzido quimicamente , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores de Glicosídeo Hidrolases , População do Leste Asiático , Tiazolidinas , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/induzido quimicamente , Biguanidas/efeitos adversos , Insulina , Demência/induzido quimicamente , Fatores de RiscoRESUMO
BACKGROUND: An increased risk of fracture has been reported in older adults taking hypnotics. However, few studies have reported the comparative safety of hypnotics with different mechanisms of action. We examined the risk of fracture in older adults initiating suvorexant compared to those initiating Z-drugs. METHODS: We conducted a retrospective cohort study using a claims database within a longevity improvement and fair evidence (LIFE) study in Japan (1.5 million beneficiaries). People aged ≥65 years were included in this study. Exposure was defined as the initiation of either suvorexant or Z-drugs (eszopiclone, zolpidem, or zopiclone). The evaluated outcomes were hip fracture and all-cause fracture requiring hospitalization. We used inverse probability of treatment weights to adjust for confounding and followed the incidence of the outcome for three different periods: 30, 90, and 365 days. Cox proportional hazards models were fitted to the weighted population to estimate hazard ratios (HRs). Sensitivity analyses were performed with narrowed outcome definitions and inverse probability of censoring weights. RESULTS: We identified 16,148 suvorexant new users and 54,327 Z-drugs new users. During the 30-day follow-up, 21 (16.6 events per 1000 person-years) and 53 hip fractures (12.2 events per 1000 person-years) were identified among suvorexant and Z-drugs new users, respectively (HR: 1.01, 95% confidence interval [CI]: 0.58-1.76). The analysis for all-cause fracture showed an HR of 1.03 (95% CI: 0.78-1.36). Extended follow-up (90 and 365 days) showed similar results for both outcomes. Sensitivity analyses showed consistent results except for an increased risk of all-cause fracture requiring surgery (HR: 1.41, 95% CI: 0.87-2.29) during the 30-day follow-up. CONCLUSIONS: This is the first study to show that suvorexant has a generally comparable risk of fracture as compared to Z-drugs. Further research is needed to investigate the potential short-term increased risk of all-cause fracture requiring surgery among suvorexant initiators.
Assuntos
Fraturas do Quadril , Longevidade , Humanos , Idoso , Estudos Retrospectivos , Vida Independente , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Hipnóticos e Sedativos/efeitos adversosRESUMO
INTRODUCTION: Hip fractures among older people are a major public health issue, which can impact quality of life and increase mortality within the year after they occur. A recent observational study found an increased risk of hip fracture in subjects who were new users of tramadol compared with codeine. These drugs have somewhat different indications. Tramadol is indicated for moderate to severe pain and can be used for an extended period; codeine is indicated for mild to moderate pain and cough suppression. OBJECTIVE: In this observational study, we compared the risk of hip fracture in new users of tramadol or codeine, using multiple databases and analytical methods. METHODS: Using data from the Clinical Practice Research Datalink and three US claims databases, we compared the risk of hip fracture after exposure to tramadol or codeine in subjects aged 50-89 years. To ensure comparability, large-scale propensity scores were used to adjust for confounding. RESULTS: We observed a calibrated hazard ratio of 1.10 (95% calibrated confidence interval 0.99-1.21) in the Clinical Practice Research Datalink database, and a pooled estimate across the US databases yielded a calibrated hazard ratio of 1.06 (95% calibrated confidence interval 0.97-1.16). CONCLUSIONS: Our results did not demonstrate a statistically significant difference between subjects treated for pain with tramadol compared with codeine for the outcome of hip fracture risk.
Assuntos
Fraturas do Quadril , Tramadol , Idoso , Analgésicos Opioides/efeitos adversos , Codeína/efeitos adversos , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/epidemiologia , Humanos , Dor/tratamento farmacológico , Qualidade de Vida , Tramadol/efeitos adversosRESUMO
BACKGROUND AND AIM: Association between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases. METHODS: This was a population-based, propensity-matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta-analysis in the electronic health record (EHR) databases. RESULTS: In the Korean National Health Insurance Service (NHIS)-CDM database, long-term PPI users had greater risk of osteoporosis [PPIs vs non-PPIs groups, 28.42/1000 person-years vs 19.29/1000 person-years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22-2.15; P = 0.001]. The meta-analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28-1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS-CDM database (PPI vs non-PPI groups, 3.09/1000 person-years vs 2.26/1000 person-years; HR, 1.45; 95% CI, 0.74-2.80; P = 0.27). However, in the meta-analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04-3.19). CONCLUSIONS: Long-term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.
Assuntos
Fraturas do Quadril , Osteoporose , Estudos de Coortes , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Humanos , Estudos Multicêntricos como Assunto , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine. METHODS: Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death. RESULTS: Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0-6.7) to 8.1 (4.9-11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0-1.4) to 1.5 (1.3-1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7-3.7) and HR (95% CI) of 1.7 (1.3-2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4-3.4) and 1.7 (0.2-3.3), respectively, and HRs (95% CI) of 1.6 (1.2-2.0) and 1.4 (1.1-1.9), respectively. No differences were observed between tramadol and NSAIDs for all events. CONCLUSIONS: OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.
Assuntos
Doenças Cardiovasculares , Fraturas do Quadril , Osteoartrite , Tramadol , Tromboembolia Venosa , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Codeína/efeitos adversos , Estudos de Coortes , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diclofenaco/uso terapêutico , Feminino , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/epidemiologia , Humanos , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Tramadol/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologiaRESUMO
OBJECTIVE: Once-yearly infusions of zoledronic acid (ZA) 5 mg may be optimal for secondary fracture prevention after hip fracture (HF), but there are crucial side effects of ZA. This study assessed the tolerability of the first infusion of once-yearly ZA within one to two weeks after HF surgery and to identify risk factors for acute-phase reactions (APRs) and the decrease in serum calcium (Ca) concentration. METHODS: We analyzed 84 patients (average age: 83 years, 18 men and 66 women) who met the inclusion criteria. The patients underwent the first infusion of ZA one to two weeks after HF surgery and received antipyretic analgesics and active vitamin D analog. RESULTS: APRs occurred in ten patients (11.9%) and all these patients had pyrexia (>37.5 °C) and/or other symptoms. The asymptomatic hypocalcemia (serum Ca < 8.3 mg/dL) incidence was 6.0% at 7 days after ZA infusion. Compared with female patients without APRs, female patients with APRs had significantly higher levels of serum 25-dihydroxyvitamin D at baseline and serum C-reactive protein on the day ZA was administered (day 0). Multiple linear regression analyses showed that serum level of tartrate-resistant acid phosphatase-5b were significantly associated with an absolute decrease in serum corrected Ca from day 0 to day 7. CONCLUSIONS: The first infusion of ZA within one to two weeks after HF surgery was well tolerated with the combined use of antipyretic analgesics and active vitamin D analog. Higher inflammatory condition after surgery which is more likely sensitized by ZA administration may increase the risk of APRs, and high bone turnover may increase hypocalcemia risk.
Assuntos
Antipiréticos , Conservadores da Densidade Óssea , Fraturas do Quadril , Hipocalcemia , Osteoporose , Idoso de 80 Anos ou mais , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/cirurgia , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/tratamento farmacológico , Imidazóis/efeitos adversos , Masculino , Osteoporose/tratamento farmacológico , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Ácido Zoledrônico/efeitos adversosRESUMO
Concerns have been raised over the association between bisphosphonates and atypical fractures in subtrochanteric and femoral shaft regions, but the potential risk of these fractures due to bisphosphonate use in asthma has not been examined. INTRODUCTION: Bisphosphonates are used as first-line treatment for osteoporosis; however, concerns have been raised over their association with atypical subtrochanteric (ST) and femoral shaft (FS) fractures. The potential risk of atypical ST/FS fractures from bisphosphonate use in asthma has not been examined. METHODS: A nested case-control study was conducted using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we identified patients with atypical ST/FS fractures and sex, age, and practice-matched controls. Conditional logistic regression was used to determine the association between bisphosphonate exposure and atypical ST/FS fractures. RESULTS: From a cohort of 69,074 people with asthma, 67 patients with atypical ST/FS fractures and 260 matched control subjects were identified. Of the case patients, 40.3% had received bisphosphonates as compared with 14.2% of the controls corresponding to an adjusted odds ratio (aOR) of 4.42 (95%CI, 2.98 to 8.53). The duration of use influenced the risk with long-term users to be at a greater risk (> 5 years vs no exposure; aOR = 7.67; 95%CI, 1.75 to 33.91). Drug withdrawal was associated with diminished odds of atypical ST/FS fractures. CONCLUSION: Regular review of bisphosphonates should occur in patients with asthma. The risks and benefits of bisphosphonate therapy should be carefully considered in consultation with the patient. To improve AFF prevention, early signs which may warrant imaging, such as prodromal thigh pain, should be discussed.
Assuntos
Asma , Conservadores da Densidade Óssea , Fraturas do Fêmur , Fraturas do Quadril , Asma/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Estudos de Casos e Controles , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Quadril/induzido quimicamente , HumanosRESUMO
The aim of this study is to investigate the impact of bisphosphonate treatment on the prognosis of patients with initial hip fracture. Patients aged fifty years and older with initial hip fracture were identified from the Taiwan National Health Insurance Research Database between 2002 and 2011. A multi-state model was established to evaluate the transition between "first to second hip fracture", "first hip fracture to death", and "second hip fracture to death". Transition probability and cumulative hazards were used to compare the prognosis of initial hip fracture in a bisphosphonate treated cohort versus non-treated cohort. In addition, Deyo-Charlson comorbidities, both vertebral and non-vertebral fractures, and cataracts were also included for analysis. After 10-year follow-up, there is decreased cumulative transition probability for both second hip fracture and mortality after both first and second hip fracture in the bisphosphonate treated cohort. Multivariable, transition-specific time-dependent Cox model revealed that bisphosphonate treatment significantly reduced risk for second hip fracture in the first 5 years of the treatment (HR 0.88; 95% CI 0.79-0.99; P: 0.034), first hip fracture mortality (HR 0.88; 95% CI 0.83-0.93; P < 0.001), and second hip fracture mortality in the first 2 years of the treatment (HR 0.78; 95% CI 0.65-0.95; P = 0.011). Female sex, both vertebral and non-vertebral fractures, cataracts, dementia in the first 2 years, and DM with complication were all significantly associated with risk of a second hip fracture. Cerebrovascular disease and hemiplegia comorbidities had less risk of a second hip fracture. The risk of mortality after both first and second hip fracture was significantly associated with congestive heart failure, renal disease, myocardial infarction, and moderate to severe liver disease. Our study demonstrated that bisphosphonate treatment and strict management of comorbidities after the initial hip fracture significantly decrease the risk for a second hip fracture and mortality.
Assuntos
Difosfonatos , Fraturas do Quadril , Idoso , Estudos de Coortes , Difosfonatos/uso terapêutico , Feminino , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Coluna VertebralRESUMO
BACKGROUND: People with dementia are a high-risk group for hip fractures. Although the increased risk of hip fractures associated with antipsychotic drugs (APD) is found in older populations, little is known about the risk for people with dementia living in Asia. We aimed to investigate the association between hip fractures and the characteristics of APD use in patients with dementia. METHODS: A nested case-control analysis was conducted on a nationwide cohort in Taiwan. People with diagnoses of dementia during 2003-2012 were identified. Conditional logistic regression analysis was performed, and adjusted odds ratios (aORs) were calculated with a 95% confidence interval (CI) to estimate the risk of hip fractures. RESULTS: APD use was associated with an increased risk of hip fractures in patients with dementia; current use or combined use of first and second generations of APDs had even higher risks. Regarding the duration of APD use, a U-shape curve of hip fracture risk was noted, and the risk peaked during 0-15 days and >215 days of exposure (aOR = 1.46, 95% CI 1.37-1.57; aOR = 1.47, 95% CI 1.37-1.58; respectively). Considering the doses of APDs, the hip fracture risk was significantly increased with all four levels of the cumulative doses and average daily doses and peaked in the group with the highest average daily dose. CONCLUSIONS: The findings suggest that caution must be taken when initiating APD use in patients with dementia, even in a small dose, and mixed types of APD prescriptions should be administered with care. Furthermore, frequent evaluation of the possibility of tapering or withdrawal of the medication is necessary, as the risk does not attenuate after long-term use.