The association between compliance and persistence with bisphosphonate therapy and fracture risk: A review

BACKGROUND: Sub optimal levels of compliance and persistence with bisphosphonates are potentially compromising the reduction of post menopausal osteoporotic (PMO) fracture risk. METHODS: A structured literature search (1990–2006) was performed to identify primary research studies evaluating the relationship between compliance and persistence with bisphosphonates and post menopausal osteoporotic (PMO) fracture risk in clinical practice. Search criteria were: bisphosphonates; osteoporosis/osteopenia in postmenopausal women; all types of fractures; compliance and persistence. RESULTS: Only two retrospective studies using prescription databases have specifically evaluated bisphosphonates. A cohort study tracking 35,537 women reported that in those with a Medication Possession Ratio (MPR) of ≥80% over 24 months the risk of fracture was lower than in those with an MPR of <80% (8.5% v 10.7%, p < 0.001, Relative Risk Reduction (RRR) 21%). In women who persisted with treatment (refill gap <30 days) the risk of fracture was also lower (7.7% v 10.3%, p < 0.001, RRR 29%). A nested case control study reported that 12 months persistence (refill gap <50% previous prescription (Rx) length) was associated with a 26% reduced risk of fracture (p < 0.05) and 24 months with a 32% reduced risk (p < 0.05). Four other studies, not specific to bisphosphonates, reported that compliance ≥12 months decreased fracture risk by ~25%. CONCLUSION: Sub optimal compliance and persistence with bisphosphonates is not providing the best possible protection against the risk of PMO fracture, however, more research is needed to delineate this relationship in clinical practice.