Guidance issued for long-term bisphosphonate use

The American Society for Bone and Mineral Research released guidance on the optimal duration of long-term bisphosphonate therapy in patients with osteoporosis.

The guidance appeared in the January 2016 Journal of Bone and Mineral Research.

The American Society for Bone and Mineral Research commissioned a task force to review the available literature on the efficacy and potential harms of long-term bisphosphonate therapy in order to provide guidance for the duration of treatment and develop a clinically based algorithm that incorporates individual patient risk for osteoporotic fracture.

The society's task force suggested that after 5 years of oral bisphosphonate or 3 years of intravenous bisphosphonate therapy, clinicians should reassess risk. In women at high risk—for example, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture or a fracture on therapy—continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered.

“The risk of atypical femoral fracture, but not osteonecrosis of the jaw, clearly increases with bisphosphonate therapy duration, but such rare events are outweighed by vertebral fracture risk reduction in high-risk patients,” the guidance stated. “For women not at high fracture risk after 3 to 5 years of bisphosphonate treatment, a drug holiday of 2 to 3 years can be considered.”

The suggested approach for long-term bisphosphonate use is based on limited evidence in which sustained fracture efficacy was demonstrated only for vertebral fractures, was based on mostly white postmenopausal women, and does not replace the need for clinical judgment, the guidance noted. It may also apply to men and patients with glucocorticoid-induced osteoporosis, with some adaptations. It is unlikely that future trials will provide data for formulating definitive recommendations.

Two trials provided the majority of the evidence for long-term bisphosphonate use. The first was the Fracture Intervention Trial Long-term Extension (FLEX), in which postmenopausal women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years. The second was the HORIZON extension, in which women who received 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years. Low hip T-score, between –2 and –2.5 in FLEX and below –2.5 in HORIZON extension, predicted a beneficial response to continued therapy.

“It is obvious that there is relatively little evidence on which the Task Force can base recommendations, and indeed we have presented management suggestions based on limited data and clinical experience,” the guidance concluded.

The authors noted that the risk of atypical femoral fractures is low, with an incidence of up to 50 per 100,000 person-years during the first 5 years of bisphosphonate use, resulting in a clear positive benefit/risk ratio within this time frame. However, although the risk of atypical femoral fractures increases further with prolonged bisphosphonate use, reaching up to 113 per 100,000 person-years after 8 to 9 years, there is much less certainty about these estimates, the guideline stated. Furthermore, sustained fracture efficacy with prolonged bisphosphonate use has been shown for vertebral fracture only. Shared decision making should be used to continue long-term bisphosphonate therapy beyond 5 years, the task force said.