Dataset Information

Hip Fracture Risk After Treatment with Tramadol or Codeine: An Observational Study.

ABSTRACT:

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.

SUBMITTER: Voss EA

PROVIDER: S-EPMC9296392 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Hip Fracture Risk After Treatment with Tramadol or Codeine: An Observational Study.

Voss Erica A EA Ali Saberi Rana SR Singh Arun A Rijnbeek Peter R PR Schuemie Martijn J MJ Fife Daniel D

Drug safety 20220709 7

<h4>Introduction</h4>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 an ...[more]

PMID: 35810265

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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:Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ -2.5, measured from the CT scan using VirtuOst). We defined "treated" as at least six months of any osteoporosis medication by prescription fill data during follow-up; "not-treated" was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21-0.33) for women and 0.21 (0.13-0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47-1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.

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Project description:ImportanceThe increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.ObjectiveTo investigate the overall association between gabapentinoids and the risk of hip fractures and the stratified association across age groups, frailty status, and history of chronic kidney disease.Design, setting, and participantsThis was a case-case-time-control study in patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least 1 prescription for a gabapentinoid before fracture. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% CI for gabapentinoid dispensing in the index (1-60 days prefracture) compared with the reference (121-180 days prefracture) period. To adjust for the underlying time trend in gabapentinoid use, each index case was matched with up to 5 controls, selected from future cases of the same age and sex. Subgroup analyses were conducted in subgroups with or without chronic kidney disease (CKD), frailty scores less than 5, and frailty scores 5 and above. Frailty was computed using the Hospital Frailty Risk Score (HFRS). Data were analyzed from November 2023 to April 2024.ExposureGabapentinoids (pregabalin or gabapentin).Main outcome and measureHip fracture.ResultsOf 28 293 patients hospitalized for hip fractures, 2946 (1752 [59.5%] aged ≥80 years; 2099 [71.2%] female) were dispensed a gabapentinoid before hip fracture. Gabapentinoid dispensing was associated with increased odds of hip fractures (OR, 1.96; 95% CI, 1.66-2.32). After adjusting for the exposure-time trend and concomitant use of other central nervous system medications, the odds of hip fractures remained elevated (OR, 1.30; 95% CI, 1.07-1.57). The association between gabapentinoid dispensing and hip fracture was higher in patients with HFRS 5 and above (OR, 1.75; 95% CI, 1.31-2.33) and CKD (OR, 2.41; 95% CI, 1.65-3.52).Conclusions and relevanceIn this case-case-time-control study of Australian residents hospitalized for hip fracture, gabapentinoid use was associated with an increased risk of hip fractures, especially in patients who were frail or had chronic kidney disease. In addition to the known risk associated with kidney impairment, frailty status may be an important risk factor when considering use of gabapentinoids.

Dataset Information

Hip Fracture Risk After Treatment with Tramadol or Codeine: An Observational Study.

Introduction

Objective

Methods

Results

Conclusions

Publications

Hip Fracture Risk After Treatment with Tramadol or Codeine: An Observational Study.

Similar Datasets

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