Risks and benefits of bisphosphonate use in patients with chronic kidney disease: a population-based cohort study

Application Number
Lay Summary

Kidney disease is associated with a significantly increased risk of broken bones (fractures) with substantial implications for patients, NHS and society.
Although there are effective drugs (i.e. bisphosphonates) that reduce fracture risk in patients with osteoporosis (brittle bones), these drugs are untested in patients with kidney disease.

In addition some data suggests that these bone therapies may worsen kidney function. Indeed, patients with kidney disease were under-represented or excluded from most trials, leaving a gap in the current medical knowledge.

To address this, we propose to use ‘real life’ data as routinely collected in NHS primary and hospital clinical practice (the called CPRD linked to HES database), linked to the UK Renal Registry data, with detailed information on end-stage kidney disease.

As this is an observational study and the data have already been routinely collected whenever a patient is seen in any NHS facility, patients will not need to be randomized to receive bisphosphonates or any other treatment including “water pills” (placebo). Therefore, this approach will avoid exposing patients with kidney function impairment to unnecessary risks such as bisphosphonate-related potential adverse events.

Technical Summary

With the aging population a growing number of patients are living with kidney disease. Although osteoporosis and fragility fractures are common amongst chronic kidney disease (CKD) patients, the effectiveness and safety of first-line anti-fracture therapies (bisphosphonates) for this population are still unclear. Indeed, patients with kidney disease were under-represented or excluded from most randomised clinical trials, leaving a gap in the current medical knowledge about the potential benefits and risks of these medications in this growing group of the population.

To address this, we intend to use CPRD/HES data linked to the UK Renal Registry data, with detailed information on kidney disease. We aim to study the association between oral bisphosphonate (OB) use in CKD patients and the following: CKD worsening (or need for renal dialysis or transplant), bone fracture/s, adverse events, and bone density (a measurement of bone strength).

Health Outcomes to be Measured

The specific aims are to study, in the population with stage ≥3B CKD (eGFR<45 ml/min/1.73m2), the following:

● The association between the use of oral bisphosphonates and the progression (stage worsening or entering renal replacement therapy/transplant) of kidney disease.

● The relationship between oral bisphosphonate use and incident symptomatic fractures.

● The risk of adverse events (upper gastro-intestinal events, hypocalcemia/hypophosphatemia, or acute kidney injury) amongst users of oral bisphosphonates, compared to matched non-users.


Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Andrew Judge - Collaborator - University of Oxford
Anne Felicity Thompson - Collaborator - National Osteoporosis Society ( NOS )
Antonella Delmestri - Collaborator - University of Oxford
Cyrus Cooper - Collaborator - University of Southampton
Daniel Dedman - Collaborator - CPRD
Denise Abbott - Collaborator - National Kidney Federation
Fergus Caskey - Collaborator - University of Bristol
Leena Elhussein - Collaborator - University of Oxford
Muhammad Javaid - Collaborator - University of Oxford
Nigel Arden - Collaborator - University of Oxford
Sanni Ali - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yoav Ben-Shlomo - Collaborator - University of Bristol


HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation