Endocrine Abstracts

Introduction: The maximum period of bisphosphonate use has not been determined, as their long-term appliance has been associated with adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF).

The aim of this study was to systematically present existent data regarding the effect of bisphosphonate discontinuation on fracture risk and bone mineral density (BMD).

Methods/design: MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to December 2016) for randomized placebo-controlled trials.

Results: Regarding alendronate, five studies fulfilled eligibility criteria (“drug holiday”: two-five years). Extending alendronate (5–10 mg/d) use to five years, after continuous treatment for five years, reduced clinical vertebral fracture risk by 55%, without difference in morphometric vertebral or non-vertebral fractures (one study). Lumbar BMD remained higher than pre-treatment levels in the discontinuation group, although lower compared with the extension group. Hip BMD decreased or remained unchanged.

Regarding zoledronic acid, two studies fulfilled eligibility criteria. After three annual infusions (5 mg/y), extending treatment to six years reduced risk of new morphometric vertebral fractures by 49%, without benefit in clinical vertebral or other types of fractures. Lumbar BMD remained above pre-treatment values in the discontinuation group, but reduced in hip sites. Extending treatment to nine years provided no additional benefit.

Regarding risedronate, one study fulfilled eligibility criteria. Discontinuation for one year (after 5 mg/d for three years) did not increase non-vertebral fracture risk, but continued to confer a reduced risk in vertebral fractures (46%). Lumbar BMD remained higher, whereas femoral neck BMD decreased, compared with pretreatment levels. No increased risk of ONJ or AFF was shown in these studies.

Conclusions: A “bisphosphonate holiday” may be considered after five years of treatment with alendronate, three with risedronate and three with zoledronic acid for up to five, one and three years, respectively. However, this decision should be individualized.