Network meta-analysis of anti-osteoporosis therapies for oral glucocorticoid users

Study Type: Meta-analysis/Systematic Review
OE Level of Evidence: 2
Journal Level of Evidence: N/A
27 randomized controlled trials that examined 9 different active treatments were included in this network meta-analysis to evaluate the efficacy of various treatments compared to placebo plus calcium and vitamin D in the treatment of patients with glucocorticoid-induced osteoporosis. Outcomes assessed in this network meta-analysis were incidence of vertebral fractures, incidence of non-vertebral fractures, and bone mineral density at the lumbar spine and femoral neck. The results of Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Non-funded
Conflicts: Consultant
Why was this study needed now?
Chronic treatment with glucocorticoids can lead to glucocorticoid-induced osteoporosis and osteoporotic fracture. Several drugs that are used in the treatment of osteoporosis are approved for the prevention and treatment of glucocorticoid-induced osteoporosis. However, the comparative efficacy of these treatments has not been assessed through a systematic review of the high-quality literature available on the topic, and the number of treatments and trials that do not provide direct comparisons highlight the need for a network meta-analysis.
What was the principal research question?
Among oral glucocorticoid users, what are the comparative efficacies of the various anti-osteoporosis drugs - including calcitonin, bisphosphonates, denosumab, teriparatide, and hormone replacement therapy - compared to placebo for fracture risk and bone mineral density increase?
Data Source: The search strategy was supplemented from a previously conducted search used for a 2010 guideline on prevention and treatment of glucocorticoid-induced osteoporosis. The strategy was altered for publication date up to March 30, 2015, and also to search for articles related to denosumab, which had previously not been searched for. was also searched for in-process or unpublished studies. Lastly, reference lists of identified articles were hand searched for any additional studies missed by the electronic search.
Index Terms: Full search strategy can be found in the appendix of the full publication.
Study Selection: Eligibility criteria included: a double-blind randomized controlled trial design; enrolled participants >18 years of age prescribed oral glucocorticoid; enrolled a minimum of 15 patients per group; randomized participants to treatment arms receiving calcitonin/calcitriol, vitamin D, bisphosphonates (alendronate, etidronate, risedronate, ibandronate, zoledronate), denosumab, teriparatide, or raloxifene, and a control arm receiving placebo, placebo plus calcium, placebo plus calcium and vitamin D or one of the aforementioned drugs (head-to-head trials); performed a minimum of 6 month follow-up; and reported outcomes of bone mineral density and fracture incidence. A total of 27 RCTs (25 placebo-controlled; 2 head-to-head) were selected for final inclusion.
Data Extraction: Data was extracted independently by two reviewers, with disagreements resolved through consensus.
Data Synthesis: Analyses were performed using WINBUGS. A bayesian network meta-analysis was performed, with mean differences calculated for continuous outcomes and risk ratios for dichotomous outcomes, both with 95% credible intervals (CrI). Additionally, treatment ranking was performed using SUrface under the Cumulative RAnking curve (SUCRA) statistics from Markov Chain simulations.
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.