There are no prospective data showing nonvertebral fracture reduction—as there are for alendronate and risedronate. However, there was a time when we had only vertebral fracture data on those compounds; a leap of faith was necessary to prescribe them for overall fracture prevention.
The MOBILE study employed a randomized, double-blind method referred to as a “noninferior” trial. A total of 1,609 women with osteoporosis were assigned to once-monthly or daily oral ibandronate. All monthly regimens proved “noninferior” to daily dosing, and the highest monthly dose (150 mg) proved superior to the daily regimen, in terms of lumbar spine BMD increase at 1 year. All regimens were similarly tolerated.
Those who would criticize this methodology will be interested to recall that noninferiority trials were exactly the mechanism that led the way from daily to weekly dosing for alendronate and risedronate.
Which patients are best suited to ibandronate?
Until nonvertebral fracture data become available, however, many clinicians may feel that ibandronate is best suited for these patients:
- women who feel that even once weekly dosing is too inconvenient, and
- younger postmenopausal women who are not at high or immediate risk for hip or other nonvertebral fractures.
- Chesnut CH III, Skag A, Christiansen C, et al for the Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE). Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19:1241–1249.
- Delmas PD, Recker RR, Chestnut CH III, et al. Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int. 2004;15:792–798.
- Reginster JY, Felsenberg D, Cooper C, et al. A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate. Osteoporos Int. 2005 Jun 14; [Epub ahead of print].
Martino S, Cauley JA, Barrett-Connor E, et al for the CORE Investigators. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96:1751–1761.
- In postmenopausal women at high risk for breast cancer who also need bone pharmacotherapy, raloxifene offers an additional benefit in the breast as well as in the skeleton.
How low can you go?
The MORE trial failed to show a reduction in hip fracture. However, the rate of hip fracture in the placebo group was very low (0.7%) compared to that of placebo groups in an alendronate trial known as FIT I (2.2% placebo group) and the risedronate trial (3.9% placebo group) conducted by McClung and colleagues. This finding underscores the notion that it is difficult to lower risk if a group’s risk level is initially low.
Efficacy after 8 years. The Continuing Outcomes Relevant to Evista (CORE) study, which included 5,213 women, extended the MORE trial for 4 years. The primary endpoint was new-onset invasive breast cancer. After 4 years of the original MORE trial, the incidence of invasive breast cancer among patients given raloxifene was reduced 72% compared to that among patients given placebo. At the end of 8 years, the incidence of invasive breast cancer and estrogen-receptor positive breast cancer were reduced by 66% and 76%, respectively, compared with placebo.
A second chance
Unlike tamoxifen (the original selective estrogen receptor modulator [SERM]) whose use in women with breast cancer is limited to 5 years, raloxifene has no time limit.
ADDITIONAL REFERENCES
- American College of Obstetricians and Gynecologists. Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39. Obstet Gynecol. 2002;100:835:835–844.
- Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–1541.
- Delmas PD, Ensrud KE, Adachi JD, et al for the Multiple Outcomes of Raloxifene Evaluation Investigators. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2002;87:3609–3617.
- McClung MR, Geusens P, Miller PD, et al for the Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333–340.