10611 Background: Bone metastases are the most frequent malignant disease of the bone and are responsible for high morbidity and reduced quality of life in cancer patients. Zoledronic acid (Zometa, Zol), routinely used in this subgroup of patients, inhibits bone resorption and has antitumor properties. It has also been reported to have an antiangiogenic effect.
METHODS
The study prospectively evaluated the levels of RANK, RANKL and OPG transcripts by real-time PCR in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Patients were eligible if they were at first diagnosis of bone metastases and if they had not previously undergone treatment with bisphosphonates. All patients received the standard Zol schedule of a 4-mg infusion every 28 days. Patients were monitored for about 12 months and blood samples were collected before the first infusion of Zol and every 4 months thereafter.
RESULTS
At least 3 blood samples were taken from all 49 patients (4 samples were taken from 29). Baseline RANK, RANKL and OPG median values were 78.3 (range 7.3-620.6), 319.1 (21.4-1884.4) and 1.52 (0.1-58.0), respectively. At 12 months RANKL median value had decreased by 22% with respect to baseline, whereas OPG median value had increased by about 96%. Consequently, the RANKL/OPG ratio decreased by 56% with respect to baseline. These differences, however, did not reach statistical significance, perhaps due to the small case series evaluated. Conversely, although RANK median values had increased by 36% at 8 months with respect to baseline, they had returned to near baseline values at 12 months. OPG, RANK and RANKL/OPG trends were significantly related.
CONCLUSIONS
The present work is one of the few prospective studies to be carried out on circulating markers that are potentially correlated with bone metastases. It was observed that markers of the RANK/RANKL/OPG pathway in the peripheral blood of bone metastasis patients were probably modulated by Zol treatment. Zoledronic acid would appear to decrease osteoclast activity both directly and also via RANK/RANKL/OPG pathway modulation. Further investigation of the biological results is warranted.