Findings from a review in the Annals of Internal Medicine provide important insight about the benefits and risks of long-term use of bisphosphonates and the effects of discontinuing treatment on fracture prevention.
Researchers analyzed data from 48 studies that enrolled men or postmenopausal women aged 50 or older who were being investigated or treated for osteoporosis or osteopenia (low bone mass). The studies compared use of osteoporosis drug therapy for more than three years with placebo or another treatment, or compared drug continuation with discontinuation or drug holidays.
Treatment with alendronate for four years reduced the risk of vertebral (spinal) and nonvertebral fractures in women with osteoporosis, while four years of treatment with raloxifene reduced the risk of vertebral fractures only. Zoledronic acid treatment for six years reduced the rate of both types of fractures in women with osteopenia or osteoporosis. Two trials showed that after treatment with alendronate or zoledronic acid for three to five years, there were fewer clinical and radiographic vertebral fractures. There was no difference in nonvertebral fracture risk after an additional three to five years of treatment compared with discontinuation.
Long-term bisphosphonate use (particularly after seven or eight years) was associated with an increased risk for atypical femoral fractures and osteonecrosis of the jaw, but these adverse events were very rare. More data are needed to assess drug holidays and treatment in men.