Bone markers in the management of patients with skeletal metastases

BACKGROUND. Biochemical markers of bone remodeling have been used as surrogate markers to manage patients with metastatic bone disease. Markers of the bone resorptive process, such as the bone collagen breakdown products N-telopeptide and C-telopeptide, are useful markers for monitoring the response and efficacy of antiresorptive therapy and to assess disease progression in patients with osteolytic bone disease. Recently discovered markers of osteoclastogenesis, osteoprotegerin (OPG) and the soluble form of the receptor activator for nuclear factor (NF)-κB (RANK-L), also are candidate markers of the bone metastases process and offer potential as surrogate markers of tumor-induced osteoclastogenesis. METHODS. Immunoassays have been developed that can determine blood and urine levels of the telopeptides associated with bone collagen breakdown. In addition, immunoassays now are available that can measure both OPG and the soluble form of RANK-L in blood and tissues as markers of osteoclastogenesis. RESULTS. The measurement of bone collagen breakdown products and specific factors associated with the process of osteoclastogenesis have been applied to the management and assessment of patients with metastatic bone disease. Results indicate that these surrogate markers can be useful in determining response to antiresorptive therapy, in selecting optimal dosage, and as markers of disease progression. CONCLUSIONS. Although they show promise, questions remain whether blood measurements of surrogate markers of osteoclastogenesis, like OPG and RANK-L, will be useful in both assessing and managing patients with metastatic bone disease.