Objective: To compare the effectiveness in reducing the risk of hip fracture between alendronate and raloxifene.

Rationale: Osteoporosis is characterized by decreased bone mass and deterioration of bone tissue, resulting in reduced bone strength and increased fracture risk. Approved therapies for osteoporosis include bisphosphonates, calcitonin, raloxifene and teriparatide. Among these drugs, alendronate and raloxifene are the most popular osteoporosis medication and a burden of prescription are performed annually.

A definitive study comparing the effectiveness of alendronate and raloxifene was limited. The Evista alendronate comparison (EVA) trial was designed to be the first double-blind, randomized comparison trial to compare osteoporosis therapies head-to-head for fracture risk reduction among 3,000 postmenopausal women. However, the study enrollment was stopped early due to difficulties with timely recruitment of treatment women. Foster et al. conducted a retrospective database study comparing the fracture rate and breast cancer rate between alendronate and raloxifene groups. However, the adverse outcomes associated with alendronate such as atypical fracture, esophageal cancer, osteonecrosis of jaw, and adverse outcome associated with raloxifene such as increased risk of venous thromboembolic event were not investigated.

Therefore, we thought that the evaluation of hip fracture rate in patients of taking osteoporosis medications (alendronate or raloxifene) and of adverse outcomes in using osteoporotic medication are necessary with a large population study.

In the study described here we will utilize the OHDSI network to compare the effectiveness in reducing the risk of hip fracture between alendronate and risedronate, and to evaluate the adverse reactions of both medications.

Project Lead(s): Yeesuk Kim, MD, PhD; Marc A. Suchard, MD, PhD

Coordinating Institution(s): Hanyang University; University of California, Los Angeles

Additional Participants: Jon Duke; George Hripcsak; David Madigan; Christian Reich; Patrick Ryan; Martijn Schuemie;

Full Protocol: GoogleDocs

Initial Proposal Date: March 21, 2017

Launch Date: April 4, 2017

Study Closure Date: April 18, 2017

Results Submission: Via AWS S3 bucket