Bisphosphonates: when the right question does not fit the system
24th September 2026
Dominic Nutt is a patient advocate and communications consultant, co-founder of Patient Powered Research and a guest editor of a forthcoming special issue of Bioethics on participant-funded research. With Alexander Masters, he co-authored A Plutocratic Proposal, (Journal of medical Ethics 2017) which examines an ethical model for participant-funded clinical trials, and has a longstanding interest in how promising but commercially neglected research can be taken forward.
Some of medicine’s most interesting opportunities may already be sitting on pharmacy shelves. They have been noticed. But the questions they raise do not always fit the system built to answer them.
Take bisphosphonates, for example. They have been used for more than 50 years, chiefly to treat bone loss. At Oxford, James Edwards and colleagues are investigating whether their effects extend beyond bone.
In one six-year randomised trial of zoledronate involving 2,000 older women, those receiving the drug had fewer fractures, fewer cardiovascular events and a lower incidence of cancer. There was also a possible reduction in mortality. Other work has examined pneumonia and earlier-stage research has explored neurodegenerative conditions including Alzheimer’s and Huntington’s diseases.
These findings are not proof that bisphosphonates prevent those diseases or extend life. Several were not the trial’s primary outcomes, and the evidence is not equally strong across every condition. However, they are signals that are important enough to investigate, if not yet strong enough to guide treatment.
The virtue that looks like a problem
The conventional trial system has good reasons to favour one treatment, one indication and one manageable primary endpoint. That discipline allows researchers to determine whether a treatment caused an effect. Ageing research does not make it dispensable.
But ageing is not organised by medical specialty. Processes such as cellular senescence, inflammation and declining repair operate across tissues and may contribute to several diseases. If an intervention influences one of those processes, effects across multiple conditions are not distracting complications. Their breadth may be the most important fact.
For bisphosphonates, the question potentially crosses bone health, cardiovascular disease, cancer, pneumonia, mortality and neurodegeneration. Studying each outcome separately may obscure their common biology. Loading them all into one trial may make the research unwieldy or prohibitively expensive.
The existing system is not wrong. It simply has no obvious home for research that sits between and across its established categories.
Who owns a cross-cutting question?
Bisphosphonates are generic drugs, with limited intellectual property available to protect. The commercial incentive to finance a definitive trial is therefore weak. Disease charities, academic departments and conventional funding streams are also commonly organised around individual conditions. Establishing whether bisphosphonates could prevent several age-related diseases might have enormous public benefit. Yet no single institution or funding stream is responsible for answering that question.
This is why BSRA matters
BSRA’s role is not to champion bisphosphonates or relax scientific standards. It is to create the forum in which the whole question can be seen before it is divided into rigorous, answerable parts.
That means connecting ageing biologists with clinical researchers, trial designers, statisticians, regulators, funders and specialists in generic medicines and intellectual property. It means allowing evidence from one disease or discipline to inform another, while remaining clear about uncertainty.
Bisphosphonates may eventually produce a therapeutic advance or a well-founded negative result. Either would be valuable. The failure would be leaving the question unanswered because what ageing research recognises as a connected biological system is treated elsewhere only as a collection of unrelated endpoints.