Effectiveness of oral bisphosphonates in reducing fracture risk among oral glucocorticoid users: three matched cohort analyses

The benefit of oral bisphosphonates in reducing fracture risk among in glucocorticoid-induced osteoporosis is controversial. We aimed to estimate the effectiveness of oral bisphosphonates in reducing fracture risk in a cohort of new chronic oral glucocorticoid users. We created three matched cohorts using healthcare administrative data from Ontario, Canada. We included residents aged 66 years and older initiating chronic oral glucocorticoids (≥450 mg prednisone equivalent and ≥ 2 GC prescriptions within a 6-month window) between January 1998 and September 2014. Exposed patients were those who initiated an oral bisphosphonate (alendronate, etidronate, or risedronate) within the first 6 months of starting chronic oral glucocorticoid therapy. Exposed cohorts (3,945 alendronate, 5,825 risedronate, and 8,464 etidronate) were each matched 1:1 to unexposed patients on GC exposure, fracture risk factors, and propensity score. We examined incident hip (primary outcome), vertebral, forearm and humerus fractures using Cox proportional hazard models. Alendronate (HR = 0.46, 95%CI: 0.25 – 0.80) and risedronate (HR = 0.58, 95%CI: 0.36-0.90) were associated with reduced hip fracture risk. Alendronate (HR = 0.49, 95%CI: 0.34 – 0.69), etidronate (HR = 0.58, 95%CI: 0.45-0.73) and risedronate (HR = 0.43, 95%CI: 0.32-0.59) were associated with reduced vertebral fracture risk. No risk reduction in forearm or humerus fractures was apparent for any bisphosphonate. Among older chronic glucocorticoid initiators, all oral bisphosphonates reduced vertebral fracture risk, yet only alendronate and risedronate reduced hip fracture risk. Results were similar between men and women. We provided compelling evidence that early initiation of oral bisphosphonates during the chronic glucocorticoid therapy is beneficial to reduce osteoporotic fractures.