Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

Abstract

BackgroundThis study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.MethodsOne hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations.ResultsPatients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%).ConclusionAI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.

Assessment of Aromatase Inhibitor-Induced Bone Loss and Appropriateness of Supportive Therapy in Postmenopausal Breast Cancer Patients at a Tertiary Care Center

“…Benefit of IV zoledronic acid is that it can bypass the disadvantages, such as gastrointestinal intolerance, inadequate compliance, and poor bioavailability of orally administered bisphosphonates. [29] Even though other bisphosphonates may also be equally effective, parenteral zoledronic acid was the only bisphosphonate used (off-label) in our patients.…”

Bisphosphonates and Prevention of the Perimenopausal Breast Cancer Recurrence: A Systematic Review and Meta-Analysis

“…In recent years, the role of BPs in skeletal-related events in patients with breast cancer and metastatic bone disease has been investigated [ 42 43 ]. BPs increase the bone mineral density of lumbar and hip joints in premenopausal and postmenopausal women with breast cancer [ 44 45 ]. Other roles of BPs have been reported in previous studies, including antitumor effects, apoptosis, reduced proliferation, and inhibition of tumor cell migration and invasion [ 46 ].…”

Letrozole and zoledronic acid changed signalling pathways involved in the apoptosis of breast cancer cells

“…Supporting this suggestion, it has been found that AI-treated breast cancer women showed an increased risk of osteoporosis and bone fractures. 23 Moreover, nitrogen-containing bisphosphonates, e.g. ZLA, were found to enhance bone mineral density in normal postmenopausal women via inhibition of osteoclast-mediated bone resorption.…”