Prevention of vertebral fractures in osteoporosis: mixed treatment comparison of bisphosphonate therapies

ABSTRACT

Objective: The objective was to compare the efficacy of bisphosphonates regarding the prevention of vertebral fractures in postmenopausal women with osteoporosis.

Methods: Seven randomized placebo controlled trials investigating the effects of zoledronic acid (one study), alendronate (three studies), ibandronate (one study), and risedronate (two studies) in terms of fractures with a follow-up of 3 years were identified with a systematic literature search. The endpoint of interest was vertebral fractures. Results of all trials were analyzed simultaneously with a Bayesian mixed treatment comparison (MTC). With MTC the relative treatment effect of one intervention to another can be obtained in the absence of head-to-head evidence. MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics.

Results: There is a 98% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all four bisphophonates compared. Zoledronic acid showed an OR of 0.28 (95% Credible Interval 0.22; 0.35) relative to placebo, an OR of 0.57 (0.36; 0.92) relative to ibandronate, an OR of 0.54 (0.39; 0.75) relative to alendronate, and an OR of 0.49 (0.34; 0.69) relative to risedronate. Alendronate, ibandronate, and risedronate showed comparable vertebral fracture reductions. Indirect comparisons using a conservative random effects model supported these findings.

Conclusion: An indirect comparison of findings from placebo controlled randomized studies indicates that zoledronic acid provides a greater vertebral fracture risk reduction in postmenopausal women with osteoporosis than ibandronate, alendronate, or risedronate.

Key words: :

• Bisphosphonates
• Indirect comparison
• Meta-analysis
• Osteoporosis
• Vertebral fractures

Transparency

Declaration of funding

This study was funded by Novartis Pharma AG.

Declaration of financial/other relationships

J.J. and G.B. have disclosed that they are employees of Mapi Values and that Mapi Values received consultancy fees from Novartis related to this work. J.H. and M.O. have disclosed that they are employees of Novartis.

All peer reviewers receive honoraria from CMRO for their review work. The peer reviewers have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors have disclosed that they enlisted no assistance in the preparation of this manuscript.