TABLE II.

Overview of placebo-controlled trials of bisphosphonates in advanced breast cancer

Trial	Bisphosphonate	Dose	Results
Paterson et al., 1993 9	Clodronate	Oral, 1600 mg daily	Reduced the event rate of vertebral fractures and deformity, and the combined event rate for all events.
Kristensen et al., 1999 8	Clodronate	Oral, 400 mg twice daily	Reduced the number and significantly delayed the time to first SRE.
Tubiana–Hulin et al., 2001 10	Clodronate	Oral, 1600 mg daily	Significantly delayed the time to first bone event and significantly reduced pain intensity and analgesic use.
Hortobagyi et al., 199811	Pamidronate	Intravenous, 90 mg every 3–4 weeks	Reduced the incidence and delayed the onset of SREs.
Theriault et al., 199913	Pamidronate	Intravenous, 90 mg every 4 weeks	Reduced skeletal morbidity and the incidence of SREs and delayed the onset of SREs.
Lipton et al., 2000 14	Pamidronate	Intravenous, 90 mg every 3–4 weeks	Reduction in the percentage of patients with >1 SRE, median time to first SRE extended by nearly 6 months, and reduction in the mean skeletal morbidity rate was found.
Hultborn et al., 199915	Pamidronate	Intravenous, 60 mg every 4 weeks	Significantly fewer SREs
Conte et al., 1996 16	Pamidronate	Intravenous, 45 mg every 3 weeks	Effective in delaying the time to progression of bone lesions.
Body et al., 200317	Ibandronate	Intravenous, 2 or 6 mg every 3–4 weeks	Significantly reduced the smpr by 20% and extended the time to first SRE.
Body et al., 200418	Ibandronate	Orally, 50 mg daily	Significantly reduced the smpr as compared with placebo in a combined analysis.
Tripathy et al., 200419	Ibandronate	Orally, 20 mg or 50 mg daily	Significantly reduced the smpr as compared with placebo.
Kohno et al., 200512	Zoledronic acid	Intravenous, 4 mg every 4 weeks	Significant multiple event analysis demonstrated a 44% reduction in the risk of developing a SRE.

sre = skeletal-related event; smpr = skeletal morbidity period rate.