ReviewPrognostic Significance of Bone Markers in Patients With Lung Cancer Metastatic to the Skeleton: A Review of Published Data

The presence of bone metastases significantly affects clinical outcome and quality of life parameters in patients with lung cancer. In this review, we aimed to evaluate the predictive value of markers of bone turnover in skeletal morbidity and clinical parameters, including disease-free survival (DFS) and overall survival (OS), in patients with lung cancer metastatic to the skeleton who were receiving bisphosphonate treatment. A comprehensive overview of all articles published from 1995 to date in 3 medical databases (PubMed, Scopus, and Cochrane) was performed using the keywords bone markers and lung cancer. Most bone formation markers (including bone alkaline phosphatase [bALP], osteocalcin [OC], and osteoprotegerin [OPG]), most bone absorption markers (including urinary calcium, osteopontin [OPN], receptor activator of nuclear factor κ-B ligand [RANKL], tartrate-resistant acid phosphatase isoform-5b [TRACP 5b]), and the metabolites of type I collagen had elevated concentrations in patients with lung cancer and bone metastases compared with patients without skeletal involvement. Two large studies showed that urinary N-terminal telopeptide (NTX) levels are a valid diagnostic method for early detection of bone metastases and a more consistent prognosticator than bALP. Treatment with zoledronic acid reduces NTX, TRACP-5b, RANKL, and OPG levels. Furthermore posttherapeutic reduction of urinary NTX levels seems to correlate with lower risk of skeletal-related events (SREs). Levels of markers of bone remodeling reflect the presence of bone metastases and may contribute to early detection of occult skeletal disease or monitor the effect of bisphosphonate treatment. However their ability to predict SREs, as well as DFS and OS, remains debatable.