Risks and benefits of long-term bisphosphonate therapy.

Purpose: The risks and benefits of long-term bisphosphonate therapy were reviewed.

Summary: Bisphosphonates are used first line in the treatment of osteoporosis due to their demonstrated ability to reduce the risk of fracture. Benefits on bone mineral density (BMD) and fracture prevention appear to be sustained for 7-10 years; however, the lack of clinical trials extending beyond this treatment period has raised the question of how long therapy should be continued. Furthermore, some reports have suggested the potential for an increased risk of fragility fractures due to oversuppression of bone turnover with long-term bisphosphonate use. Though rare, these fragility fractures appear to have a specific fracture pattern and tend to occur after 3-8 years of bisphosphonate therapy. The use of a drug holiday has been considered as an option to avoid this risk. Data suggest that bisphosphonates have a residual therapeutic effect after being stopped and that fracture benefit appears to be sustained 2-5 years after discontinuation. This sustained benefit, however, was observed only in women with good adherence who were treated with bisphosphonate therapy for at least 2 years and whose BMD was not in the osteoporotic range before discontinuation.

Conclusion: The benefits of long-term bisphosphonate therapy in patients at high risk of fracture likely outweigh the risks. In lower risk patients, such as those with a BMD in the osteopenic or normal range after two to five years of treatment and no history of fracture, consideration could be given to stopping therapy for two to five years.