Common Questions
How do you judge the strength of evidence that a therapy reduces osteoporotic fractures?
The best study is a randomized control trial of fracture rate. There are two main issues in determining strength of evidence:
- Study design
- Primary versus secondary endpoints
Study design. This is the most important factor. Randomized control trials provide the strongest evidence for any outcome. Observational studies, like cohort and case control studies, are subject to biases. These may include the "healthy user bias" and the possibility that another factor explains the association.
Primary vs. secondary endpoints. We can measure fracture (primary endpoint) and bone mineral density (secondary endpoint). Because we are most concerned about fracture rate, the best evidence for a given therapy is measured against this outcome. For example, fluoride increases BMD, but the fracture rate actually increases. This demonstrates the importance of measuring the primary endpoint, i.e., fracture, and not relying on secondary endpoints.
Hierarchy of evidence for osteoporosis treatment effectiveness:
- RCT with fracture as the measured endpoint
- RCT with BMD as the measured endpoint
- Observational study with fracture as the endpoint
- Observational study with BMD as the measured endpoint