Comparison of risedronate, alendronate, zoledronate, and ibandronate in those with low BMD

Study Type: Meta analysis
OE Level of Evidence: 2
Journal Level of Evidence: N/A
A total of 27 randomized controlled trials were included in this network meta-analysis investigating the comparative efficacies of bisphosphonates - including alendronate, ibandronate, risedronate, and zoledronic acid - versus placebo or control in patients with low bone mineral density. All studied drugs demonstrated significant effects on vertebral fracture incidence and bone mineral density of the femoral neck; effects sizes of both outcomes were observed to be greatest with zoledronic acid. Ibandronate was the Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Non-Industry funded
Sponsor: National Institute for Health Research Health Technology Assessment Programme
Conflicts: None disclosed
Why was this study needed now?
One of the most common classes of pharmacological interventions prescribed for low bone mineral density associated with osteoporosis and osteopenia is bisphosphonates. Among them, most commonly used include alendronate, ibandronate, risedronate, and, more recently, zoledronic acid. While each has individually been tested for efficacy through randomized controlled trials, little is known about the comparative efficacy between each due to the lack of head-to-head trials. Therefore, a network meta-analysis was needed to indirectly test comparative efficacy between various bisphosphonates for patients with low bone mineral density.
What was the principal research question?
In patients with low bone mineral density, what are the comparative effects of alendronate, ibandronate, risedronate, and zoledronic acid versus placebo or other non-active treatment with respect to femoral neck bone mineral density and fracture incidence?
Data Source: MEDLINE was searched for relevant articles published up to September 2014.
Index Terms: Search terms were not detailed in the full publication.
Study Selection: Eligibility criteria included a randomized controlled trial design and allocated enrolled individuals into a treatment group - which received either alendronate, ibandronate, risedronate, or zoledronic acid - and a control group of either placebo or other non-active comparator. The study selection was performed independently by two reviewers. A total of 27 RCTs were selected for final inclusion.
Data Extraction: Extracted data included the change in femoral bone mineral density on dual x-ray absorptiometry from baseline, and incidences of vertebral and non-vertebral fractures, as well as hip and wrist fractures, specifically.
Data Synthesis: Pairwise (direct) and network (indirect) meta-analysis was performed using WinBUGS software package. Hazard ratios were calculated in the cases of fracture rates, and the differences in mean change from baseline in femoral bone mineral density. Results were presented as posterior median treatment effect with 95% credible intervals. Surface under the Cumulative Ranking curve (SUCRA) values were also reported based on Markov simulations of the likelihood each intervention was considered the most effective.
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.