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A 72-year-old woman newly diagnosed with Alzheimer disease is prescribed an opioid for the management of back pain. According to a matched cohort study conducted to evaluate the risk of opioids in patients with Alzheimer disease, which of the following is MOST likely regarding this patient’s risk of hip fracture compared to a woman of similar age with Alzheimer disease who is not taking an opioid medication?
(A) There will be no difference.
(B) It will be increased regardless of whether she is taking a weak or strong opioid.
(C) It will be increased for the duration of her treatment with an opioid.
(D) It will not be increased if she is taking a weak opioid such as codeine or tramadol.
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Discussion
Pain is a common diagnosis in patients with dementia, including Alzheimer disease. As a result, chronic opioids are prescribed to a large number of patients with dementia. Because of altered pharmacokinetics and polypharmacy, elderly patients are thought to be more prone to the central nervous system side effects of opioids, including sedation and confusion. These side effects may increase the risk of falls among a population already at risk for falls. Previous studies have demonstrated that patients with Alzheimer disease have 2-fold the risk of hip fracture compared with age- and sex-matched controls. The authors of a recent study sought to evaluate whether opioid use in community-dwelling patients with Alzheimer disease is associated with an increased risk of hip fracture.
A matched cohort study was undertaken using patients from the MEDALZ (Medication use and Alzheimer disease) cohort, which includes people in Finland who were diagnosed with Alzheimer disease from 2005 to 2011. Patients with a history of hip fracture, prolonged hospitalization during the study period, and those taking opioids at the time of diagnosis were excluded from the study. Opioid users were matched with nonusers in a 1:1 ratio. Individuals were matched based on age, sex, and time since diagnosis of Alzheimer disease, which served as a proxy of disease severity.
A total of 4,570 patients were identified as initiating opioids during the study period and matched with 4,570 nonopioid users. Patients were followed until one of these events occurred: hip fracture, hospitalization for more than 90 days, death, or study completion (December 31, 2015). The age-adjusted incidence rate of hip fractures was 3.47 per 100 person years (95% CI, 2.62–4.33) among opioid users and 1.94 per 100 person years (95% CI, 1.65–2.22) among nonopioid users. An increased risk of hip fracture was present only during the first 2 months of opioid use.
Opioid exposure was further categorized based on class of opioids administered: mild opioids (codeine and tramadol); buprenorphine; or strong opioids (oxycodone, fentanyl, morphine, and hydromorphone). An increased risk of fracture was only present among patients who were prescribed either buprenorphine or a strong opioid.
Interestingly, patients with Alzheimer disease who were prescribed opioids were more likely to have comorbid conditions such as a history of non-hip fractures and active cancer. They were also more likely to be using other psychoactive drugs such as benzodiazepines, antidepressants, and antipsychotics. The impact of these baseline differences between the patient cohorts is not fully addressed in the statistical analysis and therefore may affect interpretation of the results. Nevertheless, this study emphasizes that the benefits of prescribing opioids for pain management need to be weighed against the potential risks, especially in a high-risk population.
Reference
1. Taipale H, Hamina A, Karttunen N, et al. Incident opioid use and risk of hip fracture among persons with Alzheimer disease: a nationwide matched cohort study. Pain. 2019;160(2):417-423. doi:10.1097/j.pain.0000000000001412
