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Association of Gabapentinoid Use With Risk of Hip Fracture
TAKE-HOME MESSAGE
- This study involving nearly 30,000 participants evaluated whether gabapentinoid use is associated with an increased risk of hip fracture. The results showed that individuals taking gabapentinoids had an increased risk of hip fracture, and this elevated risk persisted after controlling for factors such as concomitant use of other central nervous system medications. The risk was even higher among individuals with higher frailty scores or chronic kidney disease.
- Clinicians should be cautious when prescribing gabapentinoids for older adults with chronic kidney disease or those at higher risk of falls.
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
The increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.
OBJECTIVE
To 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 PARTICIPANTS
This 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.
EXPOSURE
Gabapentinoids (pregabalin or gabapentin).
MAIN OUTCOME AND MEASURE
Hip fracture.
RESULTS
Of 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 RELEVANCE
In 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.
Additional Info
Disclosure statements are available on the authors' profiles:
Gabapentinoids and Risk of Hip Fracture
JAMA Netw Open 2024 Nov 04;7(11)e2444488, MTY Leung, JP Turner, C Marquina, J Ilomäki, T Tran, K Bykov, JS BellFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Saravanan et al1 should be commended for giving us a good comparison of the efficacy of gabapentin and pregabalin. Looking at the actual results, not the commentary on the results, my take is that pregabalin was no more effective than gabapentin (a 5-point improvement in the Visual Analogue Scale with pregabalin compared with a 4-point improvement with gabapentin at 6 weeks but only a 10-point improvement in the Dermatology Life Quality Index with pregabalin compared with a 13-point improvement with gabapentin at 6 weeks) but was associated with substantially more side effects (22% of patients reporting dizziness on pregabalin compared with 9% of those on gabapentin).
The finding of more dizziness is particularly important in light of this article by Leung et al that highlights a significantly increased risk of hip fracture in older patients who are prescribed gabapentinoids. My belief is that this increased risk is due to the increased risk of falls associated with dizziness owing to the use of gabapentinoids.
Given the above considerations, my practice has started to avoid both gabapentinoids and sedating antihistamines (doxepin, hydroxyzine, and diphenhydramine) in older patients with pruritus. Instead, I use oral mirtazapine or trazodone, both of which I've found to be at least as equally effective as gabapentinoids and more effective than sedating antihistamines in relieving itch. Additionally, they are very effective sleep aids, with a much better side-effect profile that largely avoids both the risk of dizziness (and subsequent falls) and anticholinergic effects that can often present at worsening cognitive function (even at low doses of gabapentinoids or sedating antihistamines).
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