Bone markers and their prognostic value in metastatic bone disease: Clinical evidence and future directions

Background: Bone metastases are prevalent among patients with advanced solid tumors. Metastatic bone disease alters bone homeostasis, resulting in reduced bone integrity and, consequently, increased skeletal complications. Biochemical markers of bone metabolism may meet an unmet need for useful, noninvasive, and sensitive surrogate information for following patients' skeletal health. Materials and methods: Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms "bone markers" or individual bone marker nomenclature, "cancer," and "metastases." Abstracts and reports from meetings were included only when they related directly to previously published work. Only papers published in English between 1990 and 2007 were included. Results: Recent retrospective analyses with bisphosphonates, and particularly with zoledronic acid, have shown significant correlations between biochemical markers of bone metabolism levels and clinical outcomes, especially for bone resorption markers. Clinical results for biochemical markers of bone formation and resorption and other emerging markers of bone metabolism including bone sialoprotein, receptor-activator of nuclear factor-κB ligand, osteoprotegerin, and other markers are presented. However, biochemical markers of bone metabolism are not yet an established surrogate endpoint for treatment efficacy. Conclusions: Biochemical markers of bone metabolism may allow physicians to identify which patients with metastatic bone disease are at high risk for skeletal-related events or death and who may be responding to therapy. Prospective randomized clinical trials are underway to further assess the utility of markers of bone metabolism in patients with bone metastases.