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A research team from the Department of Pharmacology and Pharmacy, LKS Faculty of Medicine of the University of Hong Kong (HKUMed), has found that nitrogen-containing bisphosphonates (NBPs), a medication widely used in the treatment of osteoporosis, may significantly reduce the risk of Alzheimer’s disease and related dementias (ADRD) in older adults with osteoporosis or fragility fractures. This drug repurposing approach offers a promising avenue for the prevention of ADRD, potentially alleviating the global burden of these conditions. The research findings were published in Alzheimer’s & Dementia [link to the publication].

Dementia, including ADRD, affects over 55 million people worldwide, and is projected to reach 139 million by 2050. Recognising its profound impact, the World Health Organization has identified it as a critical health priority. Although the first batch of disease-modifying drugs to slow the progression of ADRD has recently been approved, concerns about their cost, applicability and efficacy persist. These limitations highlight the urgent need for preventive approaches that are both effective and affordable. Repurposing existing medications represents a promising and efficient strategy to address this unmet need.

Osteoporosis drug shows promise in preventing dementia
Osteoporosis and dementia frequently coexist in older adults and share several risk factors, such as advanced age, female sex and reduced physical activity. Notably, the same research team has confirmed that osteoporosis and fractures are independent risk factors for dementia and that patients with dementia are at a higher risk of falls and fractures. This interconnected relationship suggests that treating osteoporosis may help alleviate the burden of dementia.

NBPs, such as alendronate and zoledronate, are well established and commonly prescribed medications for osteoporosis. Emerging biological research indicates that the pathways affected by NBPs may also play a role in ADRD pathogenesis, implying the potential for repurposing NBPs in ADRD prevention.

Large-scale study demonstrates dual benefits of NBPs
Researchers at HKUMed conducted a large-scale study using Hong Kong’s city-wide electronic medical records, involving over 120,000 patients aged 60 and above with osteoporosis or fragility fractures between 2005 and 2020. The team found that NBP users had a 16% lower risk of developing ADRD compared to untreated patients, and a 24% lower risk compared to those who received other osteoporosis medications. The association was especially pronounced in women and patients with hip fractures. The research estimated that treating 48 patients with NBPs for five years could potentially prevent one case of dementia, underscoring the potential public health value of NBPs in high-risk populations.

Professor Cheung Ching-lung, Associate Professor, Department of Pharmacology and Pharmacy, HKUMed, remarked, ‘Our study provides evidence that NBPs may offer dual benefits in strengthening bones and reducing fracture risk, as well as potentially preventing ADRD. Their potential neuroprotective role provides an empirical basis and supports future research on the actual effectiveness of this medication in preventing or delaying cognitive decline associated with ADRD.’

‘These findings are significant as they demonstrate a potential approach for reducing dementia risk in a vulnerable population using safe and widely available NBPs. In our rapidly ageing society, these findings suggest that while waiting for the novel therapies, existing medications can also provide additional protection for high-risk populations,’ said Professor Cheung.

About the research team
The study was led by Professor Cheung Ching-lung, Associate Professor from the Department of Pharmacology and Pharmacy, HKUMed. The first author is Dr Sing Chor-wing, from the same department. Other co-authors include Professor Chan Koon-ho, Dr Patrick Chiu Ka-chun and Professor Kathryn Tan Choon-beng, from the Department of Medicine, School of Clinical Medicine, HKUMed.

Media enquiries 
Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).