The Association of oral bisphosphonate use with mortality risk following a major osteoporotic fracture in the UK

Date of Approval: 
2018-05-22 00:00:00
Lay Summary: 
Osteoporosis is the medical term for reduced bone density ("brittle bones") and is primarily seen in older men and women. It is very common, affecting one in two older women and one in every 3-4 older men. Its main consequences are bone fractures due to minimal force; with the most devastating being hip fractures. People who suffer hip fractures rarely return to normal daily life, and almost one in five will die within one-year of the fracture. The risk of death is also increased following fractures of other major (more central) bones. The most common medications for osteoporosis are oral bisphosphonates. These medications reduce fracture risk by increasing bone density, and may lower the risk of death following a fracture. Moreover, studies have identified that not all patients who have a fracture receive these medications. This may be a missed opportunity as it is expected that patients receiving medications will have better outcomes (lower death rates as well as fewer fractures) compared to those not treated. The aim of this study is to evaluate whether the use of oral bisphosphonate medications following a major osteoporotic fracture reduces mortality (death) risk.
Technical Summary: 
Objectives: To examine the association of oral bisphosphonate treatment on all-cause mortality after any hip and other major osteoporotic fractures. Design: Cohort study using the Clinical Practice Research Datalink (CPRD). Participants: Men and women aged 50 years and over who sustained a first recording of a hip, or non-hip major osteoporotic fracture following 2005 will be eligible for inclusion with prior fractures since 1994 as potential confounders. Date of fracture will define the index date (start of follow-up). Exposure: The primary drug exposure will be the initiation of oral bisphosphonate (alendronate or risedronate vs. etidronate or no) medications. Patient exposure time will be classified time dependently following fracture (index) date. Primary outcome: All-cause mortality. Statistical analyses: Cox Proportional Hazard (SAS PHREG procedure) to assess the risk of all-cause mortality associated with the current use of oral bisphosphonate medications following first hip, or non-hip major osteoporotic fracture will be conducted. Never use will be the comparator groups in all analyses, and separate models will be run based on fracture site. All primary analyses will be further stratified by gender. Secondary analyses will stratify current use by type of bisphosphonate, and follow-up time. All models will be adjusted for relevant confounders.
Health Outcomes to be Measured: 
All-cause mortality
Application Number: 

Frank de Vries - Chief Investigator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
Andrea Burden - Collaborator - ETH Zurich
Joop van den Bergh - Collaborator - Maastricht University
Piet Geusens - Collaborator - Maastricht University
Shahab Abtahi - Collaborator - Utrecht University
Tjeerd van Staa - Collaborator - University of Manchester