anticholinergic burden (ACB) and hip fracture risk

Cumulative effect of taking multiple medications with anticholinergic properties is termed anticholinergic burden (ACB) or anticholinergic load (1,2,3,4):

• common anticholinergic agents prescribed in primary care include tricyclic antidepressants, first-generation antihistamines, sedatives, antispasmodics, and medications for overactive bladder
• anticholinergic burden is increasingly recognized as a significant, modifiable risk factor for falls, associated hip fractures, and overall mortality in older adults

Mechanism of increased fracture risk

• central nervous system effects lead to cognitive impairment, sedation, confusion, slowed reaction times, and dizziness
• peripheral anticholinergic adverse effects include blurred vision (due to impaired accommodation) and orthostatic hypotension, directly increasing fall risk
• emerging evidence suggests potential long-term impacts of chronic anticholinergic exposure on bone mineral density reduction

Clinical evidence and findings

• observational cohort and case-control studies consistently report an elevated risk of hip and major osteoporotic fractures associated with rising anticholinergic scores
• systematic reviews demonstrate a clear dose-response relationship: higher scores on standardized tools (such as the Anticholinergic Risk Scale or Anticholinergic Cognitive Burden scale) correlate with exponentially higher fracture rates
• hospital-based studies indicate that an acute increase in anticholinergic burden during admission significantly elevates immediate post-discharge fracture risk
• analysis of 5 cohort studies (n=65,435) found high anticholinergic burden (HAB) linked to increased 12-month (HR 1.47; 95% CI 1.11–1.94; p=0.006) and 36-month (HR 1.45; 95% CI 1.05–2.00; p=0.02) mortality, with an overall 40% higher mortality risk in patients with HAB (HR 1.40; 95% CI 1.22–1.61; p<0.001)

Management and primary care implications

• routinely audit prescribed and over-the-counter medications in older adults using validated scoring tools (e.g., ACB scale)
• prioritize deprescribing or substituting high-risk anticholinergic agents with lower-risk alternatives during annual medication reviews
• consider co-existing risk factors such as osteoporosis, frailty, visual impairment, and environmental fall hazards when prescribing new agents

References

1. Reinold J, et al. Anticholinergic burden and fractures: a systematic review with methodological appraisal. Drugs Aging. 2020;37(12):885–897.
2. Coupland CAC, et al. Anticholinergic drug exposure and the risk of falls and fractures in older people: a population-based cohort study. BMJ. 2019;365:l2315.
3. Jamieson HA, et al. Drug burden index and the risk of fracture in older adults: a national population cohort study. J Am Med Dir Assoc. 2019;20(5):576–580.
4. British Journal of Clinical Pharmacology. Anticholinergic drug burden and adverse outcomes in clinical practice. Br J Clin Pharmacol. August 14th 2026.