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Abstract

Background:

This study aims to investigate how prescriptions change in hospitals and communities, as well as to assess the impact on the elderly with fall-related fractures.

Methods:

We retrospectively analyzed data from a single center between 2014 and 2019. The observation outcomes included the number and proportion of all FRIDs and polypharmacy used and divided into 3 cohorts based on FRIDs risk level.

Results:

In total, 109 patients were included. At admission, 76.1% were used FRIDs and 59.6% were polypharmacy. Six months later, 71.6% continued to use FRIDs and 57.8% were receiving multiple medications. There was no statistically significant difference. The results of the stratified analysis according to risk levels showed a decrease in the number of high-risk FRIDs use during hospital treatment (16.5%) compared to the before hospitalization (31.2%). However, recurrent prescribing occurred in 6 months follow-up periods (29.4%) .

Conclusions:

There was a high prevalence of FRIDs and polypharmacy in elderly patients following a fall-related fracture. Despite prescription simplification during hospitalization, FRIDs will be utilized again in the community within 6 months. Both physicians and the elderly should pay closer attention to enhance medication management and facilitate appropriate deprescribing in high-risk fall older population.

Keywords

falls elderly aged fall risk-increasing drugs (FRIDs)polypharmacy fractures

Introduction

Fall-related issues are a major worry for the elderly population and their caregivers, as well as doctors, nurses, and pharmacists, because of their high incidence and mortality rate, which increasing the burden of health care and creates new challenges for medical insurance system (Ganz & Latham, 2020; Leslie & Roe, 2003; Phelan & Ritchey, 2018). Fall-related injuries, such as fractures, are the leading cause of increased hospitalization and medical costs (Sjöberg et al., 2010). Risk factors for falling are categorized as intrinsic and extrinsic; intrinsic risk factors include characteristics of the individual such as age, gender, chronic diseases and gait disturbances; extrinsic risk factors include medications, living environment and footwear (Ambrose et al., 2013). Medication is an important modifiable risk factor for falls, including the use of fall risk-increasing drugs (FRIDs) and polypharmacy (Shaver et al., 2021). Recent studies suggested that FRIDs and polypharmacy are prevalent in patients with fall-related fractures, and the use of FRIDs did not decrease after the injuries (Hart et al., 2020). Perez and colleagues reported that FRIDs and polypharmacy were common in patients released from orthogeriatric care after hip fracture surgery in Spain (Correa-Perez et al., 2019). Kragh found that two-thirds of participants with hip fracture were prescribed FRIDs before fracture, and the number increased significantly after fracture in Sweden (Kragh et al., 2011). Another large retrospective cohort study in the United States reported an infrequently reduce of exposure to prescription drugs associated with fracture risk following fragility fracture (Munson et al., 2016).

While studies have explored these patterns in various countries, no studies have yet investigated the use of FRIDs and polypharmacy in Chinese older adults hospitalized due to fall-related fractures. Therefore, we designed this study to explore the use of FRIDs and polypharmacy before and after fall-related fractures, to determine the prevalence and changes of medication use as a potentially modifiable risk factor for falls in China.

Methods

Setting and Patients

This single-center, retrospective study included patients from November 1, 2014 to October 31, 2019: ①diagnosed with fracture due to accidental fall [according to the International Classification of diseases (ICD), the discharge diagnosis was consistent with S42, S43 S52, S62, S72, S82, S92, T84 (Supplementary)], ②over 65 years old and able to live on their own before inpatient, ③not participating in hospice care, ④patient information available in the hospital information system. Exclusion criteria: ①admission to the Intensive Care Unit (ICU) during hospitalization; ②death; ③hospitalization over 90 days; ④inpatient not due to fall or fall caused by external force; ⑤follow-up information (e.g. outpatient medication prescription) was not available 6 months before inpatient or 6 months after discharge.

Data Collection

Patients’ electronic cases were accessed in the hospital information system, and those who met the inclusion and exclusion criteria were recorded in detail in Microsoft Excel with the patient's hospitalization number, name, sex, age, height, weight, history of smoking, history of alcohol consumption, history of previous falls, history of osteoporosis, comorbid diseases (related to falls), outpatient prescribed medications within 6 months before the fall fracture, medication regimen at the time of fall admission, and after discharge from the hospital Outpatient medication prescriptions within 6 months after discharge. If the patient had multiple fracture admissions, only the information from the first fracture was recorded. Outpatient prescriptions excluded medications used for acute symptoms (e.g., flu) that were not for long-term use. Drugs were counted by drug generic name, or separately if a drug contained two or more active compounds.

Definition of FRIDs and Polypharmacy

The types of FRIDs were listed in Table 1 and could be found in the literature as well (de Vries et al., 2018; Seppala, van de Glind, et al., 2018; Seppala, Wermelink, et al., 2018). The level of fall risk was adapted from the 2018 Scottish polypharmacy guidance (third edition) (https://www.napier.ac.uk/research-and-innovation/research-search/outputs/polypharmacy-guidance-realistic-prescribing-3rd-edition), and FRIDs not listed in this guideline were considered as other risk FRIDs. FRIDs are divided into three fall-risk grades: highest-risk, moderate-risk, and lower-risk. This classification has been upon a review of the clinical evidence of medicines most commonly implicated in falls. The list of FRIDs fall risk levels and recommended dosage for the elderly are shown in supplementary Tables 2 and 3. Polypharmacy was defined as the use of ≥5 drugs, and extreme polypharmacy was considered to be the use of ≥10 drugs.

Table 1.

Use of Different Types of FRIDs Before and After Falls.

Fall risk level	Medication	Within 6 months before hospitalizationN (%)	During inpatientN (%)	Within 6 months after dischargesN (%)	p value
Fall risk level	Medication	Within 6 months before hospitalizationN (%)	During inpatientN (%)	Within 6 months after dischargesN (%)	Within 6 months before hospitalizationversusDuring inpatient	During inpatientversusWithin 6 months after discharges	Within 6 months before hospitalizationversusWithin 6 months after discharges
High-risk FRIDs	Anti-muscarinic	0 (0.0)	5 (4.6)	0 (0.0)	.063	.063	–
	Antipsychotics	4 (3.7)	0 (0.0)	3 (2.8)	.125	.250	1.000
	Antidepressants	6 (5.5)	1 (0.9)	3 (2.8)	.125	.625	.375
	hypnotics	23 (21.1)	12 (11.0)	26 (23.9)	.035^*	.018^*	.607
	Dopaminergic	5 (4.6)	1 (0.9)	5 (4.6)	.125	.125	1.000
Moderate-risk FRIDs	ACEI	6 (5.5)	1 (0.9)	5 (4.6)	.063	.125	1.000
	ARB	33 (30.3)	14 (12.8)	25 (22.9)	.001^*	.043^*	.039
	Alpha-blockers	6 (5.5)	3 (2.8)	6 (5.5)	.375	.453	–
	Beta-blockers	24 (22.0)	11 (10.1)	26 (23.9)	.011*	.007^*	.727
	Opiate analgesics	0 (0.0)	33 (30.3)	1 (0.9)	<.001^*	<.001^*	1.000
	Anti-epileptics	2 (1.8)	1 (0.9)	2 (1.8)	1.000	1.000	1.000
	Anti-arrhythmics	2 (1.8)	2 (1.8)	1 (0.9)	1.000	1.000	1.000
	Antihistamines	4 (3.7)	3 (2.8)	4 (3.7)	1.000	1.000	1.000
	Diuretics	11 (10.1)	1 (0.9)	9 (8.3)	.002^*	.021^*	.625
Low-risk FRIDs	CCB	37 (33.9)	31 (28.4)	33 (30.3)	.345	.860	.388
	H2 Antagonists	4 (3.7)	1 (0.9)	3 (2.8)	.250	.625	1.000
	PPI	9 (8.3)	23 (21.1)	7 (6.4)	.016^*	.003^*	.727
	Oral antidiabetic drugs	19 (17.4)	9 (8.3)	21 (19.3)	.021^*	.004^*	.727
	Nitrates	0 (0.0)	1 (0.9)	1 (0.9)	1.000	1.000	1.000

Note. *p < .05.

Study Variables and Analysis

The main outcome was the proportion of patients who used FRIDs and polypharmacy within 6 months before fracture, admitted to the hospital and 6 months after discharge. The secondary outcome was the dosage form and the dosage of the highest-, moderate- and lower-risk FRIDs used before fracturing. Recommend geriatric dosages were based on the Geriatrics Society 2014 edition of Geriatrics at Your Fingertip or from Uptodate or Drug Labels. Continuous variables were presented in mean ± standard deviation (Mean ± SD), and categorical variables were shown in percentages. The McNemar’s test was used to compare categorical variables. The Chi-square test was used for pairwise comparison. p < .05 indicated that the difference was statistically significant.

Results

Baseline characteristics

A total of 109 patients were included, and the basic patients information shown in Table 2. The number of female (79, 72.5%) was 2.6 times higher than male (30, 27.5%). The mean age of the patients was 79 ± 7 years, with more than half of the patients aged over 80 years (55, 50.5%). Among them, patients aged 80-84 years (33, 30.3%) were especially predominant, accounting for more than 30% of the overall. 11.5% of the patients had a history of smoking and 7.3% of the patients had a history of alcohol consumption. The percentage of patients with a previous history of falls was 6.4%. 86.2% of patients had a combination of fall-related diseases, mainly hypertension, diabetes mellitus, and coronary heart disease, at 60.6%, 30.3%, and 16.5%, respectively. Among the types of fractures in patients, femur fracture (S72) accounted for the highest percentage, which could reach 82.6%, followed by shoulder and upper arm fracture (S42) with 7.3%.

Table 2.

Basic Characteristics of the Study Population.

Characteristic	Patients (%)
Female	79 (72.5)
male	30 (27.5)
Age	years
65–69	16 (14.7)
70–74	16 (14.7)
75–79	22 (20.2)
80–84	33 (30.3)
≥85	22 (20.2)
Smoking history	12 (11.0)
Drinking history	8 (7.3)
Fall history	7 (6.4)
Combination fall-related diseases *	94 (86.2)
Hypertension	66 (60.6)
Diabetes mellitus	33 (30.3)
Dementia	6 (5.5)
Chronic obstructive pulmonary disease	2 (1.8)
Atrial fibrillation	2 (1.8)
Coronary Heart Disease	18 (16.5)
Malignant lymphatic	1 (0.9)
Cancer	10 (9.2)
Osteoarthritis	4 (3.7)
Benign prostatic hyperplasia	12 (11.0)
Moderate to severe chronic kidney disease	4 (3.7)
Cerebral infarction	9 (8.3)
Osteoporosis	13 (11.9)
Hypothyroidism	1 (0.9)
Parkinson's Disease	7 (6.4)
Epilepsy	1 (0.9)
Fracture site
S42 (shoulder and upper arm fractures)	8 (7.3)
S52 (forearm fractures)	6 (5.5)
S72 (femur fractures)	90 (82.6)
S82 (calf fractures (including ankles) fractures)	4 (3.7)
S92 (foot fractures, excluding ankles)	1 (0.9)

Combined diseases refer to diseases that increase the risk of falling, including hypertension, diabetes mellitus, dementia, chronic obstructive pulmonary disease (COPD), atrial fibrillation, coronary heart disease, malignant lymphatic disease, cancer, osteoarthritis, benign prostatic hyperplasia, moderate to severe chronic kidney disease, peptic ulcer, cerebral infarction, osteoporosis, hyperthyroidism, hypothyroidism, Parkinson's disease and epilepsy.

Use of FRIDs and polypharmacy

76.1% patients had used FRIDs and 59.6% were on multiple medications during the 6 months before they had fall-related fractures, 76.1% continued to use FRIDs during hospitalization, and 71.6% and 57.8% continued to use FRIDs and multiple medications during the six-month follow-up period after discharge, and these data were not statistically different. The results of the stratified analysis according to risk levels showed a decrease in the number of high-risk FRIDs use during hospital treatment (18, 16.5%) compared to the before hospitalization (34, 31.2%), and 6 months after discharge (32, 29.4%) (p < .05). Interestingly, there was no significant difference in the number of high-risk FRIDs users before admission (34, 31.2%) and 6 months after discharge in community (32, 29.4%). The same trend occurred for the stratified analysis of multiple (36, 33.0%) and extreme multiple (7, 6.4%) drug use, during hospitalization only, but the number of people on multiple (65, 59.6%) and extreme multiple (24, 22.0%) drugs before inpatient and 6 months after discharge (63, 57.8%; 28, 25.7%) were similar within and not significantly different. The number of people using the other subgroups (all FRIDs, intermediate risk FRIDs, low risk FRIDs, other risk FRIDs) was not significantly different before admission, during hospitalization and 6 months after discharge, and the results were presented in Table 3.

Table 3.

Number and Proportion of People Using FRIDs and Polypharmacy Before and After Falls.

Medication	Within 6 months before hospitalizationN (%)	During inpatientN (%)	Within 6 months after dischargesN (%)	p value
Medication	Within 6 months before hospitalizationN (%)	During inpatientN (%)	Within 6 months after dischargesN (%)	Within 6 months before hospitalizationversusDuring inpatient	During inpatientversusWithin 6 months after discharge	Within 6 months before hospitalizationversusWithin 6 months after discharge
FRIDs	83 (76.1)	83 (76.1)	78 (71.6)	1.000	.560	.359
High-risk FRIDs	34 (31.2)	18 (16.5)	32 (29.4)	.007^*	.034^*	.815
Moderate-risk FRIDs	55 (50.5)	53 (48.6)	49 (45.0)	.888	.689	.210
Low-risk FRIDs	48 (44.0)	52 (47.7)	46 (42.2)	.678	.488	.791
Other risk FRIDs	58 (53.2)	61 (56.0)	53 (48.6)	.771	.332	.424
Polypharmacy
≥5	65 (59.6)	36 (33.0)	63 (57.8)	<.001^*	<.001^*	.824
5~9	41 (37.6)	29 (26.6)	35 (32.1)	.081	.461	.362
≥10	24 (22.0)	7 (6.4)	28 (25.7)	.002^*	<.001^*	.424

Note. *p < .05.

Specific Analysis of Medication

The top three FRIDs used in the 6 months before fall-related fractures were calcium channel blockers (CCBs) (33.9%), angiotensin receptor antagonist (ARB) (30.3%), and beta-blocker (22.0%). During hospitalization, the top three FRIDs used were Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (not include aspirin) (39.4%), opioid analgesics (30.3%), and CCBs (28.4%). The top three FRIDs used discharge within 6 months in community were CCBs (30.3%), sedative-hypnotics (23.9%), and beta-blockers (23.9%).

Hypnotics were the most frequently prescribed medications among those using high-risk FRIDs. The present study showed a significant decrease in the use of hypnotics during hospitalization (12, 11.0%) compared with before (23, 21.1%). However, the proportion of medication users returned to the previous level within 6 months after patients were discharged to the community (26, 23.9%). Among low-risk FRIDs, the use of Proton-Pump Inhibitor (PPI) during hospitalization (23, 21.1%) was significantly increased compared to pre-hospitalization (9, 8.3%) (P < 0.05), while the use of oral hypoglycemic agents was significantly increased compared to pre-hospitalization (19, 17.4%) (P < 0.05). CCBs use was consistently the highest in the low-risk FRIDs subgroup.

Discussion

This one single center retrospective study in Chinese older adults hospitalized due to fall-related fractures found that 75% of patients were treated with FRIDS (the mean number is 2.8 ± 2.2) and 59.6% of patients were polypharmacy (the mean number is 6.3 ± 3.7) before fracture. Although the number of medicine was reduced during the hospitalization, the prevalence of consumption increased significantly at 6 months after discharge which might be associated with an increased risk of recurrent falls and fractures.

In our study, the mean number of drugs used by each elderly patients before fracture was 6.3, with a mean number of 2.8 of FRIDs, accounting for almost 44% of all the drugs used by each patient. The results are consistent with those described in other previous studies (Bennett et al., 2014; Beunza-Sola et al., 2018; Correa-Perez et al., 2019; Kragh et al., 2011). Indeed, polypharmacy is one of the risk factors associated with falls, particularly when one of the components is FRID. It is worth pointing out that the reduction of number of medicine during hospitalisation was observed while little change on the total use of FRIDs. The findings may be explained by the greater sensitisation of medical professionals in reconsidering treatment with polypharmacy when elderly patients have sustained a fall related bone fracture. It has previously been reported that the consumption of two or more FRIDs rather than polypharmacy was associated with falls (Zia et al., 2017). Other studies indicated that fall risk is associated with the use of polypharmacy, but only when at least one established FRID was part of the daily regimen (Ziere et al., 2006). This contrasts with earlier findings that using more than one medication affects the risk of injurious falls among elderly individuals whether it contains FRIDs (Helgadóttir et al., 2014). In fact, the more drugs are prescribed, higher the likelihood of FRIDs prescriptions. Recently, A longitudinal study showed that the association between polypharmacy and falls was significantly attenuated after the adjustment for FRIDs, and users of two or more FRIDs had higher risk of falls (Ramos et al., 2023). Further research is needed to determine whether the risk of falls can be effectively reduced by deprescripbing FRIDs alone, regardless of polypharmacy.

Falls can be caused by almost any drug that acts on the brain or on the circulation. Different classes of FRIDs can yield varying effects on falls due to the mechanisms of action and adverse reactions (Seppala et al., 2021). Psychotropics have been consistently associated with increased risk of falls (Seppala, Wermelink, et al., 2018; Park et al., 2015). Benzodiazepines may contribute to falls by affecting cognition and the ability to control posture (Berry et al., 2016; Rothberg et al., 2013). Antipsychotics may contribute to falls by affecting cognition, regulating blood pressure, or extrapyramidal reactions (Berry et al., 2016). While antihypertensive drugs may cause postural hypotension, balance and gait disturbances, dizziness, etc, which also associated increased risk of fall (de Vries et al., 2018). So far, clinical evidence on the effect of FRIDs on fall is spare and a majority of the studies were restricted to a limited set of mainly broad medication groups. Like in class of antihypertensive drugs as potential FRIDs, beta-blocking agents seem to have reduced fall risk, but recent evidence indicated that a subgroup of beta-blocking agents, that is, nonselective, increase a risk of falling (de Vries et al., 2018). Although the understanding the effect of FRIDs in fall risk are not fully comprehensive, it is intended to raise awareness in medicine review in high risk of fall population by classified the FRIDs in risk rank. Therefore, more intervention studies are needed to reach a better understanding of the association between FRIDs by the pharmacologic subgroups and fall risk.

Not surprisingly, in line with previous studies, the number of FRIDs used and multiple medication which was reduced during hospitalisation were reverted to pre-admission levels within 6 months of discharge, suggesting long-term drug reduction can be difficult to maintain after fracture (Boyé et al., 2017). It appears challenging to reduce the use of FRIDs. A narrative review of randomized controlled trials, which focused on interventions to reduce FRIDs use and examined fall-related outcomes as the primary outcome, revealed that most of these interventions were ineffective in diminishing FRIDs use or altering fall-related outcomes (Gray et al., 2021). A lack of compliance with the withdrawal or prescription of medications for new conditions mainly explain the finding. It is imperative not only to focus on discontinuing the use of existing FRIDs but also to proactively prevent the issuance of new FRID prescriptions. Despite recognition of this problem, our medical physicians struggles with a widespread solution. First, some FRIDs was reused mainly due to anticipation of withdrawal or relapse symptoms such as hypnotic medications in our high-risk FRIDs category. Hance, stepwise withdrawal is generally recommended in clinic practice when deprescribing antipsychotics (van der Velde et al., 2023). Second, physicians should conduct a comprehensive fall risk assessment. And non-pharmacologic treatment options may be conducted first when the patients have the problem such as insomnia and constipation. Thirdly, pharmacists need to provide medication education to patients and their cares about the possible increased risk of falls with such medications. Fourth, the high mean age of our elderly patients suggests the presence of multiple comorbidities in our study. It is very hard to withdrawal the antihypertensive drugs as the potential harm. Reducing the dose of hypotensive medications, in line with recommendations, also helps avoid hypotonia and contributes to better control of heart rhythm and, hence, reduced fall risk (Wabe et al., 2024). More research evidence was need.

Our study also had some limitations. For one thing, generalisability was limited by it being conducted at a single hospital, although rate of FRIDs and polypharmacy was relatively consistent with findings from other studies (Beunza-Sola et al., 2018; Correa-Perez et al., 2019; Kragh et al., 2011). Also medications purchased over the counter or dispensed in certain care facilities for elderly individuals were not included, although this does not substantially influence the results. Moreover, the type or quantity of FRIDs may still change with the longer following-up. Such as an increase in depression has been described in elderly patients with bone fractures which lead to a new prescription of antidepression drug (Kamholz & Unützer, 2007). Additionally, it was recently reported that 10.6% of older adults being diagnosed with Alzheimer disease related dementias in the first year after a fall contributing to new prescription (Ordoobadi et al., 2024). Hence, a long time following-up of observation or intervention for FRIDs and polypharmacy in the elderly individuals is needed.

Conclusion

There was a high prevalence of FRIDs and polypharmacy in elderly patients following a fall-related fracture. Although there was not statistical significance in the total prevalence of FRIDS before and during hospitalisation, the actual reduction was observed in almost all the FRIDs during hospitalisation which was prescribed before the fracture, particularly in the high-risk of FRIDs. However, recurrent prescribing of FRIDs occurred in spite of the known high risk of falls and fractures in these people in 6 months follow-up periods. These findings call for increased attention from care providers and health professionals to enhance medication management and facilitate appropriate deprescribing in high-risk fall older population.

Supplemental Material

sj-doc-1-ggm-10.1177_30495334251385879 – Supplemental material for Patterns of Fall Risk-Increasing Drugs and Polypharmacy in Chinese Older Adults Before and After Fall-Related Fractures: A Single Center Retrospective Cohort Study

Supplemental material, sj-doc-1-ggm-10.1177_30495334251385879 for Patterns of Fall Risk-Increasing Drugs and Polypharmacy in Chinese Older Adults Before and After Fall-Related Fractures: A Single Center Retrospective Cohort Study by Yingying Gong, Kemin Yan, Hui Zhou, Xiang Gao, Yanan Huang, Mi Yao, Liping Cui, Xiaoman Liu, Jiawei Zeng and Gang Yuan in Sage Open Aging

Footnotes

ORCID iD

Yingying Gong

Ethics Considerations

The study was granted approval by the First Affiliated Hospital, Sun Yat-sen University Ethics Committee (FAH Ethics Committee No.[2021]495).

Authors’ Contributions

Study concept and design: G.Y, J.Z. Acquisition of data/analysis and interpretation of data: Y.G, K.Y, H.Z, Y.H, XG, L.C. Drafting of the manuscript: H.Z, K.Y, X.L. Literature search: Y.G, M.Y. Critical revision of the manuscript for important intellectual content: Y.G, J.Z, G.Y. All authors have read and agreed to the published version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

No datasets were generated or analysed during the current study.

Supplemental Material

Supplemental material for this article is available online.

Disclaimer

This article reflects the views of the authors and should not be construed to represent any authorities’ views or policies.

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