Benefits of bisphosphonates after five years debated

Bisphosphonate treatment that continues beyond five years might not provide additional fracture prevention benefit, concluded a review by the FDA.

The review included three long-term extension trials in which duration of treatment ranged from six to 10 years. After pooling data, the reviewers concluded that patients who took the drugs for six or more years had similar fracture rates to those who switched to placebo during the extension trials (9.3% to 10.6% with drugs vs. 8.0% to 8.8% on placebo). “These data raise the question of whether continued bisphosphonate therapy imparts additional fracture-prevention benefit, relative to cessation of therapy after 5 years,” the FDA reviewers wrote in a perspective in the New England Journal of Medicine. Given the uncertainty, they recommended treatment decisions be based on individual assessment of risks and benefits and patient preference.

Another perspective, also published online by the New England Journal of Medicine on May 9, offered more specific advice about treatment. Based on a re-analysis of two of the trials considered by the FDA, the authors focused on risk of vertebral fractures and concluded that:

• patients with a femoral neck T score below −2.5 after three to five years of bisphosphonates are at highest risk and benefit most from continuation of drug therapy,
• patients with a score of −2.0 to −2.5 may also benefit from continued therapy and
• patients with a score above −2.0 are at low risk and unlikely to benefit from continued therapy.

These recommendations about discontinuation apply only to alendronate and zoledronic acid, the perspective authors noted. They also suggested that lower doses might be considered for long-term use, although the safety of this is unknown.