Teriparatide vertebral fracture risk reduction determined by quantitative and qualitative radiographic assessment

ABSTRACT

Objective: Most registration studies for new osteoporosis drugs have used a combination of quantitative morphometry (QM) and visual semiquantitative reading (SQ) to define vertebral fractures. However, in the pivotal teriparatide Fracture Prevention Trial (ClinicalTrials.gov Identifier: NCT00670501), vertebral fractures were previously defined only by the SQ methodology. The objective of this study was to define the effect of teriparatide on the incidence of vertebral fractures defined by QM plus SQ assessment.

Research design and methods: Radiographs from the Fracture Prevention Trial placebo- and teriparatide 20 μg/day groups were re-assessed in blinded fashion, defining incident vertebral fractures for vertebrae meeting all of the following requirements: (a) 20% decrease in height by QM, (b) a corresponding 4 mm decrease in height (c) an increase of at least one grade by visual SQ assessment by a radiologist.

Results: By this methodology, vertebral fracture risk was reduced in the teriparatide versus placebo group by 84% (RR = 0.16, p < 0.001). The risk of two or more vertebral fractures was also significantly reduced by 94% (RR = 0.06, p < 0.001). The fractures in the teriparatide group were of lesser severity than the fractures in the placebo group. The absolute benefit of teriparatide was greatest in those patients with the highest number and severity of prevalent vertebral fractures.

Conclusions: As assessed by QM plus SQ, teriparatide reduced the incidence of vertebral fractures.

Trial registration: ClinicalTrials.gov identifier: NCT00670501.

Key words: :

• Quantitative morphometry
• Semiquantitative
• Teriparatide
• Vertebral
• fracture risk

Acknowledgments

Declaration of interest: Funding was provided by Eli Lilly and Company. The authors acknowledge the unwavering efforts of Bo Fan, MD (study QM reader) and Roy Harnish, MSc (study administrator), University of California, San Francisco, CA, USA. S. P. serves as a consultant to Eli Lilly and Company. P. C. and J. H. K. are employees of Lilly. H. G. serves as a consultant and receives an honorarium from Lilly, Novartis, Servier, Roche, GSK, BMS and Wyeth. D. M. B. serves as a consultant to Lilly and Nycomed and has research contracts with Novartis, Roche, and Merck.