How Long Should Bisphosphonate Treatment be Continued For?

Bisphosphonates have been widely used to treat osteoporosis for over twenty years.

Though they generally have a good safety record, various concerns have been expressed. Some of these, such as increased risk of osteonecrosis of the jaw, have been exaggerated considering how tiny the absolute risk is. Of greater clinical relevance is the risk of so-called atypical hip fractures, which appear to be associated with prolonged treatment with bisphosphonates, particularly in those with relatively normal bone mineral density (BMD). Atypical hip fractures are rare, and any increased risk associated with bisphosphonates is outweighed by their protection against other types of fracture. Nevertheless, these risks are taken seriously, and have led to recommendations regarding prolonged treatment with these agents (see www.shef.ac.uk/NOGG/NOGG_Executive_Summary.pdf).

In essence, it is advised that following five years oral treatment with bisphosphonates (ie alendronate, risedronate and ibandronate), the need for continued treatment should be re-evaluated. This should be take the form of a repeat fracture risk assessment using a tool such as FRAX (www.shef.ac.uk/FRAX), possibly informed by a repeat DXA scan. If for example fracture risk has increased to below or close to the intervention threshold (eg 5% ten year risk of hip fracture, 20% ten year risk of major fracture), or BMD is above or close to the T-2.5 threshold of osteoporosis, a ‘drug holiday’ is recommended. Accordingly, treatment is discontinued, to be recommenced one to two years later if still indicated. In those patients who remain at high risk of fracture in spite of five years’ treatment with bisphosphonates, for example patients with multiple vertebral fractures or very low BMD, it is recommended that treatment continues indefinitely on the basis that any risks are outweighed by the benefits.