Role of Zoledronic Acid on Bone Loss by Letrozole / 한국유방암학회지

ABSTRACT

PURPOSE: The aromatase inhibitors cause bone loss by estrogen depletion. Zoledronic acid (ZA) can prevent bone mineral density (BMD) loss associated with the use of aromatase inhibitors. Accordingly interest has arisen in measuring surrogate markers of bone resorption to monitor the response of treatment of BMD loss in place of a radiologic assessment. This study was designed to determine whether ZA would prevent bone loss that is known to occur with letrozole and identified surrogate markers of bone resorption in an animal model. METHODS: In ovariectomized or sham-operated rat, we administrated ZA and letrozole to 5 different groups including a sham operation control group (OC), a group in which an ovariectomy was performed followed by saline administration (OS), an ovariectomy with ZA treatment group (OZ), an ovariectomy with letrozole treatment group (OL) and an ovariectomy with ZA and letrozole combined treatment group (OZL). The levels of serum osteocalcin, serum bone alkaline phosphatase (BALP), serum calcium and urine N-telopeptide (NTX) and BMD were estimated and compared at the same periods for each group. The distinct microscopic findings of proximal tibia at week sixteen were also compared. RESULTS: Significantly reduced levels of urine NTX and significantly increased BMD were measured in the OZ group. In the OL group no difference was seen in in BMD in comparison to the OS group. However, a significant increase in BMD was measured in the OZL group. Urine NTX levels were measured and found to be lower in the OL group and significantly lower in the OZL group. Serum osteocalcin levels were similar to each other for each group. Levels of serum calcium and BALP were significantly lower in the OZL group than in the OS group. CONCLUSION: The combination treatment with ZA and letrozole is effective in the inhibition of bone resorption and in the preservation of BMD. Measurement of serum osteocalcin, urine NTX, and BMD, levels are recommended as surrogate markers for determining the response for the treatment of bone loss.