What is the role of bisphosphonate therapy for bone health management in metastatic breast cancer treatment?

Updated: Nov 06, 2019
  • Author: Winston W Tan, MD, FACP; Chief Editor: Marie Catherine Lee, MD, FACS  more...
  • Print


In the setting of metastatic disease, bisphosphonates have little or no survival effect. However, IV bisphosphonates do appear to provide a continuous effect on bone for the duration of their use.

Controlled trials have shown that administration of a bisphosphonate is associated with a delay in the development of new skeletal-related events (SREs), thus reducing or delaying the need for palliative radiation, orthopedic surgery to address pathologic fractures, and use of narcotic analgesics. [2] For this reason, monthly administration continues for an indefinite period in breast cancer patients with bone metastasi

Results of the randomized phase 3 ZOOM trial by Amadori et al, which studied the effect of decreasing the administration of zoledronic acid from every 4 weeks to every 12 weeks during the second year of treatment, suggest that the drug maintains its therapeutic effects. The ZOOM trial included 425 patients with breast cancer who had one or more bone metastases and had completed 12-15 months of monthly treatment with zoledronic acid. [21]

After follow-up of at least 1 year, the rate of skeletal-related events per patient per year in ZOOM was 0.26 (95% confidence index [CI] 0.15-0.37) in the patients who received zoledronic acid every 12 weeks, versus 0.22 (0.14-0.29) in the patients maintained on an every-4-week schedule. The upper limit of one-tailed 97.5% CI on the 0.04 difference between the groups.was 0.17, which is lower than the non-inferiority margin. [21]

Rates of the most common grade 3-4 adverse events in the 12-week group versus the 4-week group were as follows:

  • Bone pain: 27% vs 30%
  • Nausea: 11% vs 15%
  • Asthenia: 9% vs 15%

 However, median N-terminal telopeptide concentration changed from baseline more in the 12-week group than in the 4-week group after 12 months (12.2% vs 0.0%; P=0.011).The authors recommend further investigation of this change before changing current practice. [21]

A randomized, open-label clinical trial that included 855 patients with metastatic breast cancer found no increased risk of skeletal events over 2 years in patients who received zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks. Similar results were reported in study patients with metastatic prostate cancer and multiple myeloma. The authors concluded that adminstering zoledronic acid every 12 weeks may be an acceptable option. [22]

SREs occurred in 113 patients in the 4-week group versus 119 in the 12-week group, among the 820 breast cancer patients who completed the study (hazard ratio [HR], 0.90; P = 0.43). Overall, fewer patients in 4-week group underwent bone surgery (22 vs 42; HR = 0.51; P =0.01). However, the two groups showed no significant difference in pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction. Although rates of skeletal morbidity were numerically identical in both groups, patients in the 12-week group had greater bone turnover, as indicated by higher C-terminal telopeptide levels. [22]

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!