Effect of zoledronic acid on bone loss by letrozole

Abstract

11077 Background: 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 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 intense increment of BDM in the OZ group and the OZL group and lower increment in the OL group were valued in correlation to the OS group, 31.3%, 35.0%, 10.5% and 13.0% respectively. Serum osteocalcin levels and urine calcium levels were close to each group. Serum calcium levels and BALP levels were relatively lowering in the OZ group and the OZL group than other group. Meaningfully lower levels of urine NTX were measured in the OZ group and the OZL group, 6.6% and 16.5% respectively. In the OL group levels of urine NTX were rise of 55.9%. Less cancellous bone loss and increase bone trabeculae were noted in the microscopic findings of tibia. Conclusions: The combination treatment with ZA and letrozole are effective in the inhibition of bone resorption and in the maintenance 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. No significant financial relationships to disclose.