OP0049 Systematic review of randomized controlled trials evaluating bisphosphonates for the prevention and treatment of glucocorticoid- induced osteoporosis

Abstract

Objectives: Glucocorticoid therapy is a major risk factor for osteoporosis related fractures. A meta-analysis conducted by Homik et al reported bisphosphonate therapy increased BMD in glucocorticoid- induced osteoporosis (GIO) when compared to placebo, whereas results for incident vertebral fracture did not reach statistical significance. The objective of this systematic review was to evaluate the efficacy of bisphosphonates in GIO based on randomized controlled trials (RCTs). Both placebo-controlled and active comparator trials were analyzed. Methods: Two authors screened citations from Medline (1998-2015), EMBASE (1998-2015), and Cochrane Library (1998-2015). A manual search was completed for conference proceedings from the ACR (2010- 2015), CRA (2009-2015), and ASBMR (2009-2014). We used the study by Homik et al to identify RCTs published prior to 1998. Only RCTs with a minimum prednisone dosage of 5 mg/day or equivalent and treatment duration of at least 3 months were included. Primary outcomes were changes in BMD and incident fractures. Two authors abstracted data using a standardized data abstraction form. We used the Cochrane Risk of Bias Tool to evaluate the quality of selected RCTs and devised a quality score ranging from 0 to 6, where 6 represents the highest quality. Results: A total of 466 citations were identified (239 Medline, 217 EMBASE, 10 Cochrane Library). Fourteen RCTs met the inclusion criteria. An additional two RCTs were identified from conference proceedings. Eleven RCTs compared bisphosphonate to placebo, three RCTs compared bisphosphonate to a vitamin D derivative, one RCT compared alendronate to teriparatide, and one RCT compared zoledronic acid to risedronate. RCTs were of reasonably good quality with a mean quality score of 4. Overall, of the 11 RCTs that compared bisphosphonate to a placebo, all found bisphosphonate was superior. Nine RCTs were pooled for mean percentage change in lumbar spine mean BMD (bisphosphonates n = 667, placebo n = 654). The pooled mean percentage change was in favor of bisphosphonates compared to placebo [weighted mean difference(WMD) of 4.03%, 95% CI (1.59-6.47), p = 0.001]. Six RCTs were pooled for mean percentage change in femoral neck BMD (bisphosphonates n = 486, placebo n = 481) and the results favored bisphosphonates compared to placebo [WMD of 2.95%, 95% CI (0.09 -5.82), P = 0.04]. Seven RCTs were pooled for outcome of incident fractures (bisphosphonates n = 613, placebo n = 469) and the results favored bisphosphonates compared to placebo [RR of 0.65, 95% CI (0.48-0.88), P = 0.006]. Results were pooled using RevMan (version 5.3). Conclusion: Bisphosphonates mitigate adverse changes in BMD and lower fracture risk in patients treated with glucocorticoids.