Abstract
BackgroundAnticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales.MethodsPrimary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg’s test.ResultsA total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1–2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18–1.39], 1 point; 1.12 [1.06–1.18], 2 points; 1.15 [1.08–1.23]).ConclusionsThis result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.
Highlights
Anticholinergic burden potentially increases the risk of fracture
Study selection The inclusion criteria of the present study were: (1) cohort studies or case-control studies that evaluated the association between anticholinergic drugs and fracture risk; (2) studies in which patients were administered anticholinergic drugs defined by anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale (ADS) or drug burden index-anticholinergic component (DBI-Ach); (3) fracture was defined by objective measures such as the International Classification of Diseases; (4) the association between anticholinergic drugs and fracture was assessed using either the hazard ratio (HR), risk ratio (RR) or odds ratio (OR)
ACB 1 point and ACB 2 points were associated with similar fracture risk
Summary
Anticholinergic burden potentially increases the risk of fracture. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales. A study of the trend of anticholinergic drug prescriptions from 1995 to 2010 reported an increase in prescriptions of these agents from 20.7% in 1995 to 23.7% in 2010 [1]. Patients who receive prescriptions from more than one physician potentially have an increased anticholinergic burden due to concomitant use of anticholinergic drugs. Other studies found no significant fracture risk of anticholinergic drugs [8, 9]. Whether the use of anticholinergic drugs increases the fracture risk remains controversial
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