Biochemical markers and skeletal metastases.

BACKGROUND: Skeletal metastases are common occurrences in patients with malignancies such as breast and prostate carcinoma, but they are difficult to diagnose nonradiologically, and treatment is difficult to follow clinically. Recent developments suggest that biochemical markers of bone remodeling, such as the bone collagen breakdown product N-telopeptide and the bone formation marker known as bone specific alkaline phosphatase, hold great promise as clinical tools for the management of patients with metastatic bone disease.
METHODS: Serum levels of the bone formation marker known as bone specific alkaline phosphatase (BAP), along with serum levels of the bone collagen breakdown product carboxyterminal telopeptide of Type I collagen (ICTP) and urine levels of pyridinoline (PYD), deoxypridinoline (DPD), and N-telopeptide (NTx), were measured in a large cohort of patients with newly diagnosed or progressive cancer of the breast, prostate, lung, and other sites. Bone marker levels were correlated with the presence or absence of bone scan-documented metastases; metastatic disease extension in terms of the number of skeletal sites involved; and the type of lesion, whether blastic or lytic. Sites examined included the pelvis, spine, skull, ribs, and long bones.
RESULTS: All of the bone markers examined, including BAP and NTx, were abnormally elevated in a high proportion of patients with confirmed metastases to bone. Urine NTx levels and bone specific alkaline phosphatase were significantly correlated with the number of skeletal sites involved, and a significant correlation between marker level and extent of skeletal involvement was also observed. In addition, both markers were higher in patients with a blastic disease presentation than in patients with osteolytic lesions.
CONCLUSIONS: Biochemical markers of bone resorption and bone formation are abnormally raised in the blood and urine of patients with metastatic bone disease. Markers of bone collagen breakdown, such as N-telopeptide, as well as markers of osteoblast function, such as bone specific alkaline phosphatase, appear to be of use in assessing and managing patients with malignancies that metastasize to bone. In this study, both NTx and BAP showed a significant correlation with both the presence of bone metastases and the extent of skeletal involvement. Biochemical markers of bone remodeling can also be used to guide decision making regarding the treatment of metastatic bone disease and to determine the effectiveness of therapy for patients with cancer to bone whose broad-based symptoms make it difficult to discern true response to therapy.