When a patient in her seventies brings me her medication list, alendronate is often on it, usually tucked between a blood pressure pill and a vitamin D supplement. She thinks of it as a bone drug, and her primary care physician prescribed it because of a DEXA scan or a broken wrist. Neither of them was thinking about her brain. A large study from Hong Kong, which drew fresh press coverage this month, suggests that the brain may be worth thinking about as well.
What the Hong Kong Study Found
The study, led by Ching-Lung Cheung and first author Chor-Wing Sing in the Department of Pharmacology and Pharmacy at the University of Hong Kong, was published in Alzheimer's & Dementia in July 2025, and the university released its summary of the findings on November 9, 2026. The team used Hong Kong's territory-wide electronic health record system to follow 121,492 adults aged 60 and older who had been newly diagnosed with osteoporosis or a fragility fracture of the spine, hip, wrist, or upper arm between 2005 and 2020. Anyone with a prior dementia diagnosis, dementia medication, or cancer was excluded.
The researchers compared people who started a nitrogen-containing bisphosphonate (alendronate, ibandronate, risedronate, or zoledronate) against two groups. The first group received no osteoporosis medication. The second group received a different class of osteoporosis drug: denosumab, salmon calcitonin, strontium ranelate, or teriparatide. Patients were matched one to one on a propensity score that accounted for age, sex, calendar year, fracture type, nursing home residence, medical history, and recent medications, and the analysis did not begin counting dementia cases until six months after treatment started.
Compared with untreated patients, bisphosphonate users had a hazard ratio for Alzheimer's disease and related dementias of 0.84 (95% CI 0.78 to 0.90), which is a 16 percent lower relative risk. Compared with users of other osteoporosis drugs, the hazard ratio was 0.76 (95% CI 0.66 to 0.89), or 24 percent lower. The absolute numbers are more useful to a patient. Over five years, the cumulative incidence of dementia was 2.1 percentage points lower in the bisphosphonate group than in the untreated group, which works out to a number needed to treat of 48. The association held in both women and men, and it held when the team extended the waiting period to 12 months and when they censored patients who switched drugs.
Why a Bone Drug Might Matter to the Brain
Bisphosphonates work by blocking an enzyme called farnesyl pyrophosphate synthase, which sits in the mevalonate pathway. This is the same pathway that statins act on further upstream. In bone, blocking this enzyme stops osteoclasts from breaking down bone tissue. The authors point out that two products of this pathway, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, have been found at elevated levels in brain tissue from people with Alzheimer's disease, and that a variant of the gene for this enzyme has been associated with higher levels of phosphorylated tau. In animal studies, alendronate has shown neuroprotective effects. That is a plausible mechanism, and it has been tested only in animals so far.
There is a second explanation that I find at least as interesting. Osteoporosis and dementia share many of the same risk factors, and a hip fracture in an older adult often sets off a sequence of delirium, hospitalization, immobility, and social withdrawal that the brain does not always recover from. Any drug that keeps a person upright, walking, and out of the hospital may protect cognition indirectly. Bisphosphonates also tend to concentrate in bone, and how much of the drug reaches the brain in humans remains an open question. The study cannot tell us which of these explanations is correct, and both may contribute.
What This Study Can and Cannot Tell Us
This is an observational cohort study, so the correct reading is that bisphosphonate use was associated with lower dementia risk. It does not show that the drug prevented dementia, and Professor Cheung's group says the same thing in their own release. People who start and stay on a bisphosphonate may differ from untreated patients in ways a medical record does not capture, such as education, diet, exercise, or how closely they follow their doctor's advice. The comparison against other osteoporosis drugs helps here, because both groups were sick enough and engaged enough to be treated, and that comparison produced the stronger association rather than a weaker one.
The authors also list what they could not measure: baseline cognitive function, bone mineral density, physical function, over-the-counter vitamin D and calcium, education, air pollution, and social isolation. Dementia was identified from diagnostic codes, and the population was Hong Kong Chinese, so the findings need to be confirmed in other groups. The study that would settle the question is a randomized trial that measures cognition as a primary outcome in older adults who already qualify for bone treatment. The authors have also suggested studying bisphosphonates together with statins, since both drugs act on the mevalonate pathway, and I would like to see that trial run as well.
This fits a pattern we have seen with other common drugs. In my post on amyloid clearance and tau, I wrote about how much of Alzheimer's risk is decided by factors outside the amyloid plaque itself. Vascular health, inflammation, metabolic health, and, it now appears, the condition of the skeleton all bear on how well a brain holds up with age.
What I Recommend to Patients
I would not start a bisphosphonate for brain health alone, and I would not ask a patient to do so on the strength of one observational study. These drugs carry real, if uncommon, risks, including atypical femur fractures and osteonecrosis of the jaw with long-term use, and those risks only make sense to accept when there is a bone indication.
For the many older adults who already have that indication, the picture is different. Osteoporosis is undertreated in the United States, and a large share of people who break a hip never start a bone medication afterward. If you are over 60, have had a fragility fracture, or have been told your bone density is low and you have been putting off treatment, this study gives you one more reason to have that conversation with your physician. The decision should still be individual and should depend on your fracture risk, kidney function, dental health, and your own preferences about long-term medication.
In our Intensive Brain Health Program, we look at bone health as part of brain health. A precision workup that includes advanced MRI, blood biomarkers such as p-tau217, cognitive testing, and a review of metabolic and hormonal factors should also ask whether the skeleton is holding the person up. The brain does not age in isolation from the rest of the body, and the medications a patient already takes are part of that picture.
In the Neuroeconomy, a person's cognition is the asset that a career, a family, and a legacy depend on. Protecting it means paying attention to everything that bears on it, including a bone drug that was prescribed for a completely different reason.
This article was drafted with the assistance of AI writing tools, then reviewed, edited, and approved by Dr. Sean C. Orr, M.D., who holds full editorial responsibility for its content.
Sources:
Sing, C.W., Chan, K.H., Chiu, P.K.C., Lau, W.C.Y., Zhang, X., Tan, K.C.B., Cheung, C.L. "Bisphosphonates and the risk of dementia in patients with osteoporosis or fragility fracture: A population-based study in Hong Kong." Alzheimer's & Dementia, July 21, 2025; 21(7): e70503. DOI: 10.1002/alz.70503.
University of Hong Kong LKS Faculty of Medicine. "Common osteoporosis drugs linked to 24% lower dementia risk in major study." ScienceDaily, November 9, 2026. sciencedaily.com.