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Association of Tramadol Use With Risk of Hip Fracture.

ABSTRACT: 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.

SUBMITTER: Wei J

PROVIDER: S-EPMC8282603 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:Importance:Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown. Objective:To estimate hip fracture risk associated with concurrent exposure to multiple FADs. Design, Setting, and Participants:This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019. Exposure:Receipt of prescription FADs. Main Outcomes and Measures:Hip fracture hospitalization. Results:A total of 11.3 million person-years were observed, reflecting 2 646 255 individuals (mean [SD] age, 77.2 [7.3] years, 1 615 613 [61.1%] women, 2 136 585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2 827 284 person-years (25.1%) involved receipt of 1 FAD; 1 322 296 (11.7%), 2 FADs; and 954 506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P < .001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P < .001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P < .001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P < .001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P < .001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P < .001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P < .001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P < .001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P < .001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P < .001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P < .001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P < .001). Conclusions and Relevance:Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.

Project description:ImportanceTreatment with antidepressants has been associated with hip fracture. This association could restrict the treatment options, especially in older patients.ObjectiveTo investigate the association between antidepressant drug treatment and hip fracture starting 1 year before the initiation of treatment.Design, setting, and participantsIn this nationwide cohort study, 204 072 individuals in the Prescribed Drugs Register of Sweden's National Board of Health and Welfare aged 65 years or older who had a prescription of antidepressants filled between July 1, 2006, and December 31, 2011, were matched by birth year and sex to 1 control participant who was not prescribed antidepressants (for a total of 408 144 people in the register). Outcome data were collected from 1 year before to 1 year after the index date (date of prescription being filled). Data analysis was performed from July 1, 2005, to December 31, 2012.ExposuresFirst filled prescription of an antidepressant drug.Main outcomes and measuresIncident hip fractures occurring in the year before and year after initiation of antidepressant therapy were registered. Associations were investigated using multivariable conditional logistic regression models and flexible parametric models.ResultsOf the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.Conclusions and relevanceThe present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.

Project description:ObjectivesTo determine whether the use of total hip arthroplasty (THA) among individuals with a displaced intracapsular fracture of the femoral neck is based on national guidelines or if there are systematic inequalities.DesignObservational cohort study using the National Hip Fracture Database (NHFD).SettingAll hospitals that treat adults with hip fractures in England, Wales, and Northern Ireland.ParticipantsPatients within the national database (all aged ≥60) who received operative treatment for a non-pathological displaced intracapsular hip fracture from 1 July 2011 to 31 April 2015.Main outcome measuresProvision of THA to patients considered eligible under criteria published by the National Institute for Health and Care Excellence (NICE).Results114 119 patients with hip fracture were included, 11 683 (10.2%) of whom underwent THA. Of those who satisfied the NICE criteria, 32% (6780) : received a THA. Of patients who underwent THA, 42% (4903) did not satisfy the NICE criteria. A recursive partitioning algorithm found that the NICE eligibility criteria did not optimally explain which patients underwent THA. A model with superior explanatory power drew distinctions that are not supported by NICE, which were an age cut off at 76 and a different ambulation cut off. Among patients who satisfied the NICE eligibility, the use of THA was less likely with higher age (odds ratio 0.88, 95% confidence interval 0.87 to 0.88), worsening abbreviated mental test scores (0.49 (0.41 to 0.58) for normal cognition v borderline cognitive impairment)), worsening American Society of Anesthesiologists score (0.74, 0.66 to 0.84), male sex (0.85, 0.77 to 0.93), worsening ambulatory status (0.32, 0.28 to 0.35 for walking with a stick v independent ambulation), and fifths of worsening socioeconomic area deprivation (0.76 (0.66 to 0.88) for least v most deprived fifth). Patients receiving treatment during the working week were more likely to receive THA than at the weekend (0.90, 0.83 to 0.98).ConclusionsThere are wide disparities in the use of THA among individuals with hip fractures, and compliance with NICE guidance is poor. Patients with higher levels of socioeconomic deprivation and those who require surgery at the weekend were less likely to receive THA. Inconsistent compliance with NICE recommendations means that the optimal treatment for older adults with hip fractures can depend on where and when they present to hospital.

Project description:ObjectiveTo examine the risk factors for new chronic opioid use in elderly patients who underwent hip fracture surgery.DesignProspective population-based cohort study.Setting and participantsUsing Danish nationwide health registries, we identified all opioid non-user patients aged ≥65 years who had undergone hip fracture surgery from 2005 to 2016 and were alive within the first year following surgery.Main outcome measuresNew chronic opioid use defined by the dispensing of at least two prescription opioids within two of the last three quarters during the first year following surgery.ResultsWe identified 37 202 opioid non-user patients who underwent hip fracture surgery. Of these, 5497 (15%) developed new chronic opioid user within 1 year of surgery. Risk factors for new chronic opioid use were Body Mass Index (BMI) of <18.5 (adjusted OR (aOR) 1.22, 95% CI 1.09 to 1.36), BMI of 25.0-29.9 (aOR 1.12, 95% CI 1.04 to 1.21) and BMI of ≥30 (aOR 1.57, 95% CI 1.40 to 1.76) with BMI 18.6-24.9 as reference, a pertrochanteric/subtrochanteric fracture (aOR 1.27, 95% CI 1.20 to 1.34) with femoral neck fracture as reference, preoperative use (vs no-use) of non-steroidal anti-inflammatory drug (aOR 1.68, 95% CI 1.55 to 1.83), selective serotonin reuptake inhibitor (aOR 1.42, 95% CI 1.32 to 1.53), antidepressants (aOR 1.36, 95% CI 1.24 to 1.49), antipsychotics (aOR 1.21, 95% CI 1.07 to 1.35), corticosteroids (aOR 1.54, 95% CI 1.35 to 1.76), statins (aOR 1.09, 95% CI 1.02 to 1.18), antibiotics (aOR 1.32, 95% CI 1.22 to 1.42), antiosteoporosis drugs (aOR 1.33, 95% CI 1.19 to 1.49) and anticoagulatives (aOR 1.24, 95% CI 1.17 to 1.32). Presence of cardiovascular comorbidities, diabetes, gastrointestinal diseases, dementia, chronic obstructive pulmonary disease or renal diseases was further identified as a risk factor.ConclusionIn this large nationwide cohort study, we identified several risk factors associated with new chronic opioid use after hip fracture surgery among patients who were alive within the first year following surgery. Although not all factors are modifiable preoperative, this will allow clinicians to appropriately counsel patients preoperatively and tailor postoperative treatment.

Project description:BackgroundHip fractures are a significant post-stroke complication. We examined predictors of hip fracture risk after stroke using data from the Women's Health Initiative (WHI). In particular, we examined the association between post-stroke disability levels and hip fracture risk.MethodsThe WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. Trained physicians adjudicated stroke events and hip fractures. Our study included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Scale of good recovery, moderately disabled, or severely disabled and survived more than 7 days post-stroke. Hip fracture-free status was compared across disability levels. Secondary analysis examined hip fracture risk while accounting for competing risk of death.ResultsAverage age at time of stroke was 74.6±7.2 years; 84.3% were white. There were 124 hip fractures among 4,640 stroke survivors over a mean follow-up time of 3.1±1.8 years. Mortality rate was 23.3%. Severe disability at discharge (Hazard Ratio (HR): 2.1 (95% Confidence Interval (CI): 1.4-3.2), but not moderate disability (HR: 1.1 (95%CI: 0.7-1.7), was significantly associated with an increased risk of hip fracture compared to good recovery status. This association was attenuated after accounting for mortality. White race, increasing age and higher Fracture Risk Assessment Tool (FRAX)-predicted hip fracture risk (without bone density information) were associated with an increased hip fracture risk. After accounting for mortality, higher FRAX risk and white race remained significant.ConclusionSevere disability after stroke and a higher FRAX risk score were associated with risk of subsequent hip fracture. After accounting for mortality, only the FRAX risk score remained significant. The FRAX risk score appears to identify stroke survivors at high risk of fractures. Our results suggest that stroke units can consider the incorporation of osteoporosis screening into care pathways.

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Association of Tramadol Use With Risk of Hip Fracture.

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