Bisphosphonates and the risk of dementia in patients with osteoporosis or fragility fracture: A population-based study in Hong Kong.

INTRODUCTION

Emerging evidence suggests neuroprotective effects of bisphosphonates. We aim to investigate whether nitrogen-containing bisphosphonates (NBPs) could reduce the risk of Alzheimer's disease and related dementia (ADRD).

METHODS

We identified patients aged 60+ with osteoporosis or fragility fracture in 2005-2020 from a healthcare database in Hong Kong. Patients receiving NBPs were 1:1 matched with untreated patients and those receiving other anti-osteoporosis medications ("non-NBPs") by time-dependent propensity score. Follow-up was conducted until December 31, 2021. Cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model.

RESULTS

Among 121,492 patients (NBP = 15,654, non-NBP = 6331), we matched 10,833 pairs for NBPs-vs-untreated and 3080 pairs for NBPs-vs-non-NBPs. NBP use was associated with a lower risk of ADRD compared to untreated (HR = 0.84, 95% CI = 0.78-0.90) and non-NBP (HR = 0.76, 95% CI = 0.66-0.89).

DISCUSSION: NBP use was associated with a lower risk of dementia, suggesting further studies are warranted on its potential to improve cognitive function.

HIGHLIGHTS: Nitrogen-containing bisphosphonates (NBPs) are associated with a reduced risk of Alzheimer's disease and related dementia. NBPs resulted in an absolute risk reduction of 0.007, 0.018, and 0.021 at 1, 3, and 5 years, respectively. The number needed to treat (NNT) with NBPs at 1, 3, and 5 years were 133, 56, and 48. There is potential for repurposing NBPs as a therapeutic agent for Alzheimer's disease.