In our study the levels
In our study, the levels of BALP, PINP and β-CTx in the serum were significantly (p<0.05) correlated with the number of skeletal sites involved with metastases, but there was no significant difference in the levels of BTMs among patients with olytic lesions, blastic lesions and mixed lesions. A possible explanation to these findings could be that tumors may secrete these bone regulatory proteins regardless of their location, thus circulating levels maybe elevated even when skeletal involvement has not emerged. Histomorphological results show that osteolytic and osteoblastic metastases are characterized by simultaneous resorptive and osteoblastic processes . The simultaneous increases of bone formation markers and bone ACA markers indicate that the bone formation and bone absorption occur at the same time in patients with BM.
Another feature of our research was that we used BTMs clinically to predict the risk of SREs. We found that if patients had a higher β-CTx, BALP or PINP levels at baseline, they were at a higer risk of SREs. A similar pattern was seen in an study  evaluating NTx and BALP levels for 441 patients on the placebo arms of the previously noted clinical trials of zoledronic acid in patients with BM from prostate cancer, NSCLC and other solid tumors. Patients with high NTx or BALP levels had a greater incidence of SREs compared with patients with low levels of NTx or BALP. Because survival after diagnosis of BM is relatively short for patients with NSCLC, methods are needed to predict SREs in a shorter timescale than it is possible with current imaging methods. From the results of our current study, the use of BTMs at baseline may make a major contribution to this need by identifying those patients at highest risk who warrant the highest priority for intervention to prevent SREs.
Some studies assessing the relationship between urinary NTx level and OS in NSCLC have shown that high urinary NTx levels are associated with an increased risk of death [26,35,36]. Further, recent studies have suggested that zoledronic acid and denosumab reduce baseline urinary NTx level [25,36]. Moreover, patients with NSCLC and high baseline NTx levels that were normalized after chemotherapy including zoledronic acid were found to experience longer survival compared with patients whose NTx levels remained persistently high [6,36,37]. These study inspired us to find the relation between the change of BTMs and OS. The results of a randomized prospective study would be more credible, and that is what we want to do in the future. But our finding that baseline BTMs levels were predictive of death is also important because it can be argued that baseline BTMs assessments allow more time for appropriate intervention.
Conflict of interest
Acknowledgments This study was supported by National Natural Science Foundation of China Grant (81201628).
Introduction Metastatic bone disease is the most frequent malignancy of the skeletal system . Early diagnosis of bone metastases is an important step in the management of cancer as they may cause serious endocrinologic, hematologic, neurologic and orthopedic complications and intolerable pain [2,3]. Fluorine 18-Fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) is now used as a useful imaging tool for staging, restaging and evaluation of therapy response for most cancers. The uptake mechanism of the radiopharmaceutical in bone metastases depends on the pathological increase in glycolytic activity of the malignant cells, therefore 18F-FDG shows specifically the malignancy of the bone. 18F-FDG PET/CT also contributes to the true evaluation of bone marrow involvement and soft tissue component of the metastasis . Fluorine 18–Sodium Fluoride (18F–NaF) has been introduced as a bone-seeking agent first in 1962 by Blau et al.  and approved by FDA in 1972 for detection of osteogenic activity. However it lost its popularity by the easy availability of Molibdenum-99 (Mo-99) generators and better imaging characteristics of 99mTc- for gamma cameras, with respect to the high energy photons of Fluorine-18. As PET technology spread all around the world in 1990\'s, 18F–NaF PET/CT regained interest for bone scanning . The kinetics of the radiopharmaceutical is quite useful for imaging. After intravenous injection, it is cleared out from the blood pool fast and it forms fluoroapetite crystals by chemoadsorbtion to the hydroxyapatite crystals .