A Five Year Follow Up Study of 32,000 Older Adults Found that Long Term Use of Anticholinergic Medications Increased Fracture Risk by up to 65 Percent

Professor Ki Young Son of the Department of Family Medicine at Asan Medical Center Emphasized that Efforts Should Be Made To Minimize Both the Number of Medications and the Duration of Use

▲ Professor Ki Young Son of the Department of Family Medicine at Asan Medical Center

Older adults with chronic conditions such as hypertension and diabetes often take multiple medications every day. While this is often unavoidable for disease management, a recent study has found that long-term use of multiple medications may actually increase the risk of fractures.

A research team led by Professor Ki Young Son of the Department of Family Medicine at Asan Medical Center and Professor Yeon Heo of the Department of Family Medicine at The Catholic University of Korea, Seoul St. Mary's Hospital, analyzed data from the National Health Insurance Service, tracking 32,771 adults aged 66 for up to five years. The findings showed that individuals who took medications for more than six months had a 43 percent higher risk of fractures compared to those who did not.

The risk increased further with higher exposure to anticholinergic medications. In patients with a high anticholinergic burden who continued taking such medications for more than six months, fracture risk rose by as much as 65 percent. Anticholinergic agents are commonly found in a wide range of medications, including antihistamines used for colds and allergic rhinitis, as well as treatments for overactive bladder, gastrointestinal disorders, Parkinson disease, and depression. When these substances accumulate in the body, they can cause severe dizziness, increasing the likelihood of falls and fractures.

This study is significant in that it demonstrates, using large scale national data, that long term medication use may increase the risk of fractures. While previous studies have primarily focused on the types and number of medications, this study highlights that the duration of use itself can be a key determinant of fracture risk.

The research team analyzed data from the National Health Insurance Service senior database, following 32,771 adults aged 66 who participated in the national health screening program between 2007 and 2008 for up to five years. The number of medications was categorized into four groups: 0 to 1, 2 to 4, 5 to 9, and 10 or more. Medication burden was assessed using the Korean 

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Anticholinergic Burden Scale, which quantifies the cumulative anticholinergic effects of prescribed drugs. The duration of medication use was classified into short term and long term based on a cutoff of 183 days, and its association with fracture risk was analyzed.

When analyzed by the number of medications, individuals taking five to nine drugs had a 29 percent higher risk of fractures compared to those taking zero to one medication. The researchers explained that as the number of medications increases, so does the likelihood of exposure to drugs that raise the risk of falls. Commonly prescribed medications among patients with polypharmacy, such as loop diuretics and steroids, may directly contribute to fracture risk by increasing anticholinergic burden or reducing bone density.

The impact of medication duration was even more pronounced. Among all medication users, the incidence of fractures was 7.8 percent in those who used medications for more than six months, compared to 4.9 percent in the short term use group, representing a 43 percent higher risk. Similarly, among users of anticholinergic medications, the incidence of fractures was 5.1 percent in those who took them for less than six months, but increased to 7.8 percent in those who used them for longer, corresponding to a 45 percent rise in risk. These findings suggest that even older adults who take relatively few medications may still face an elevated risk of fractures if the duration of use is prolonged.

When both medication duration and anticholinergic burden were considered together, the risk increased even further. Even among those with a low anticholinergic burden (KABS score 1 to 2), taking medications for more than six months was associated with a 55 percent higher risk of fractures. In contrast, patients with a high anticholinergic burden (KABS score of 3 or higher) who continued medication use beyond six months experienced an increase in fracture risk of up to 65 percent.

Notably, in the case of hip fractures, which are particularly serious in older adults, the number of medications alone did not show a significant association with risk. However, long term use of medications for more than six months led to a sharp increase in hip fracture risk, rising by as much as 4.25 times.

Professor Ki Young Son of the Department of Family Medicine at Asan Medical Center stated, “While previous studies have focused on the association between the number and types of medications and fracture risk, this study is meaningful in that it confirms the impact of medication duration on fracture risk through long term observation.” He added, “Healthcare providers should make efforts not only to reduce the number of prescribed medications but also to minimize the duration of use.”

The findings of this study were recently published in 'BMC Geriatrics', a leading international journal in the field of geriatric medicine.