The Protective Effect of Zoledronic Acid on Bone Loss in Postmenopausal Women with Early Breast Cancer Treated with Sequential Tamoxifen and Letrozole: A Prospective, Randomized, Phase II Trial

Abstract

Objective: This study reports the efficacy and safety of zoledronic acid (ZOL) in preventing bone loss in postmenopausal patients receiving an aromatase inhibitor (AI) following tamoxifen. Methods: Postmenopausal patients with stage I–III hormone receptor-positive breast cancer who received tamoxifen for 2.5–3 years were randomized to receive letrozole (2.5 mg/day) with (n = 47) or without (n = 43) ZOL (4 mg i.v. every 6 months) for 2 years. The primary endpoint was percent change from baseline in lumbar spine (LS) bone mineral density (BMD) up to 60 months. Results: Ninety patients (86 evaluable) with a median age of 59 years (42.9–83.6), 50/86 of whom had previously been treated with chemotherapy, were followed for a median time of 41.4 months. While the control group showed a significant decrease in LS T-score (p = 0.0005), the ZOL group presented an increase over time (p = 0.0143). Change over time in LS T-score was significantly different between groups, favoring ZOL (p < 0.0001 at 24 and 48 months). No fractures, renal dysfunction or osteonecrosis of the jaw were reported. The toxicity profile was similar to those previously reported for each drug. Conclusion: The addition of ZOL to letrozole was safe and efficacious in maintaining LS BMD in postmenopausal patients with hormone receptor-positive breast cancer and who were receiving letrozole following 2.5–3 years of tamoxifen.

Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus

“…The incidence of ONJ in oncology patients treated with i.v. BPs ranges from 0 to 12,222 per 100,000 patient‐years, and the incidence of ONJ in oncology patients treated with Dmab ranges from 0 to 2,316 per 100,000 patient‐years …”

Bisphosphonates in the Adjuvant Setting of Breast Cancer Therapy—Effect on Survival: A Systematic Review and Meta-Analysis

“…Bisphosphonates have been shown to be effective in numerous studies in preventing cancer treatment-associated bone loss in postmenopausal women with early breast cancer [42]–[44] mainly due to their effect on the highly activated osteoclasts. Of note, the increase in bone loss is 5-fold higher following treatment with aromatase inhibitors (AIs) than physiological bone loss observed in postmenopausal women with established osteoporosis in the absence of AI therapy, and further induce bone turnover than documented during tamoxifen use [45]–[49]. A recent study by Cheung indicated that the effect of aromatase inhibitors (exemestane) on bone density may be underestimated and that exemestane increases cortical bone permeability thus predisposing the patient to loss of bone strength and non-vertebral fractures [50]–[51].…”

Bisphosphonates in the adjuvant setting of breast cancer therapy: Effect on survival—A systematic review and meta-analysis.

“…Bisphosphonates have been shown to be effective in numerous studies in preventing cancer treatmentassociated bone loss in postmenopausal women with early breast cancer [42][43][44] mainly due to their effect on the highly activated osteoclasts. Of note, the increase in bone loss is 5-fold higher following treatment with aromatase inhibitors (AIs) than physiological bone loss observed in postmenopausal women with established osteoporosis in the absence of AI therapy, and further induce bone turnover than documented during tamoxifen use [45][46][47][48][49]. A recent study by Cheung indicated that the effect of aromatase inhibitors (exemestane) on bone density may be underestimated and that exemestane increases cortical bone permeability thus predisposing the patient to loss of bone strength and non-vertebral fractures [50][51].…”