The bisphosphonate agent risedronate appears to reduce fracture risk during treatment for as long as 7 years; however, introduction of a 1-year drug holiday appears not to have any serious adverse effects on bone health, according to long-term results of 2 large, randomized clinical trials.

The Vertebral Efficacy with Risedronate Therapy (VERT) multinational trial demonstrated significant reductions in vertebral fractures and improvement in bone mineral density (BMD) for postmenopausal women with established osteoporosis who were treated for 3 years with risedronate. ¹ The original study was followed by a 2-year extension, during which patients continued their assigned therapy. Additional follow-up showed that the benefits achieved during the first 3 years were maintained during extension. ²

At the end of the first extension, patients had the option of entering a second extension phase that consisted of open-label therapy. Unpublished results suggest that the low fracture rate in patients initially randomized to risedronate were maintained during the second follow-up.

"I think 5 years of therapy certainly is effective," University of Cincinnati osteoporosis specialist Nelson Watts, MD, said at the 26 th annual meeting of the American Society of Bone Mineral Research in Seattle. "There is no way of knowing whether patients need to take the drug for 5 years to see the benefit or whether the first 6 or 12 months of therapy set up the benefit. However, those who continued to take the drug continued to have the anti-fracture benefit."

Dr. Watts added that "patients who continued on therapy for 7 years had the same low annualized fracture rates that they had during the first 3 years and during the first extension. It appears that continued therapy might be beneficial through 7 years."

The VERT North American trial was a placebo-controlled trial that randomized patients to 3 years of therapy and demonstrated a significant anti-fracture benefit in favor of risedronate. ³ At the end of the trial, patients ended randomized therapy and were maintained on supplemental calcium. During the first year after the study ended, patients initially treated with risedronate had a decrease in vertebral BMD, but they did not decline to the level of the control group, according to Dr. Watts.

"On the basis of the data from the VERT North American trial, a 1-year drug holiday would be reasonable for patients who have an increase in bone density and no evidence of fracture," Dr. Watts said. For patients with little or no increase in BMD, as well as for those who have fractures and those who are on long-term glucocorticoid therapy, he would recommend continued therapy.

References:

1. Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11:83-91.

2. Sorensen OH, Crawford GM, Mulder H, et al. Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone. 2003;32:120-126.

3. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. JAMA. 1999;282:1344-1352.