Effects of chemotherapy and zoledronic acid on bone metabolism measured by the osteoclast specific TRAP level in patient with bone metastases due to lung cancer

Abstract

19069 Background: Imaging and clinical assessment are often inadequate to fully predict the effect of biphosphonates. Tartrate Resistant Acid Phosphatase - 5b (TRAP) has been found to be a very specific maker of osteoclast activity. This study examines the effect of zoledronic acid and chemotherapy on TRAP levels and N-telopeptides of type I collagen (NTx). Methods: Lung cancer patients with bone metastases received monthly zoledronic acid. Serum TRAP levels and NTx levels were tested at baseline and every 2 weeks for the first two months, then monthly. The levels were tested while patients were on and off chemotherapy for lung cancer. Results: Seventeen patients were enrolled. Forty-five blood samples were tested. The mean of TRAP levels while on chemotherapy and zoledronic acid increased from 2.1 U/L to 2.41 U/L over time. In contrast the mean of TRAP levels while on zoledronic acid alone decreased from 1.98 U/L to 1.18 U/L. The difference was statistically significant (p<0.05). The NTx values ranged from 27–101 nMBCE (normal:8–23 nMBCE), and correlated with TRAP levels at 0.59 (p=0.06) Conclusions: The present study was undertaken to evaluate TRAP levels in lung cancer patients with bone metastases treated with zoledronic acid. The unexpected increase in TRAP levels in patients receiving chemotherapy and zoledronic acid, suggests that chemotherapy increases the osteoclast activity and decreases bone mass. After completion of chemotherapy, TRAP levels decreased with continuation of zoledronic acid. The drop in TRAP levels confirms that zoledronic acid has a significant inhibitory effect on osteoclast activity in patients with bone metastases, which would explain the beneficial effect of zoledronic acid on skeletal related events in previous studies. The rise in the TRAP levels in a few patients, despite zoledronic acid, off chemotherapy, could be a marker of poor response to therapy and disease progression. Further studies are needed to evaluate the correlation between skeletal related events and TRAP levels and the effect of chemotherapy on bone metabolism. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis