Vertebral fractures are associated with height loss, reduced quality of life and increased mortality, and are an important endpoint for osteoporosis trials. However, height loss is associated with quality of life and mortality independent of associations with fracture.
We have used data from a recent 6-year trial of zoledronate in 2000 osteopenic women aged >65 years to assess the impact of the semi-quantitative and quantitative components of the definition of vertebral fracture on the outcome of that trial, to determine what factors impacted on height loss, and to test whether height loss can be used as a surrogate for vertebral fracture incidence.
In the trial protocol, an incident vertebral fracture was defined as a change in Genant grade plus both a 20% and 4 mm decrease in a vertebral height. The addition of the quantitative criteria reduced the number of fractures detected but did not change the size of the anti-fracture effect (odds ratios of 0.49 versus 0.45) nor the width of the confidence intervals for the odds ratios. Multivariate analysis of baseline predictors of height change showed that age accelerated height loss (P < 0.0001) and zoledronate reduced it (P =0.0001). Incident vertebral fracture increased height loss (P = 0.0005) but accounted for only 0.7% of the variance in height change, so fracture could not be reliably inferred from height loss. In women without incident vertebral fractures, height loss was still reduced by zoledronate (height change: zoledronate, -1.23; placebo -1.51 mm/year, P <0.0001). This likely indicates that zoledronate prevents a subtle but widespread loss of vertebral body heights not detected by vertebral morphometry. Since height loss is associated with quality of life and mortality independent of associations with fracture, it is possible that zoledronate impacts on these endpoints via its effects on vertebral body integrity.