State of the Art of Biochemical Markers in Metastatic Bone Disease and the Role of Bisphosphonates as Therapeutic Agents

Ioannis      Kanakis; Achilleas   D.   Theocharis; Argiris   V.   Noulas; Nikos   K.   Karamanos

Abstract

Metastatic spread of cancer to bone is a frequent complication in several types of malignancies. Normal bone metabolic process is affected and the imbalance between bone formation and resorption defines bone disease in cancer. The major causes of the secondary development of the disease is either the cancer cell itself (metastatic or non-metastatic) or cancer therapies. Early diagnosis of bone metastatic disease is very important for the survival of patients. The dominant disadvantage of imaging techniques used for detection of bone metastases is that they are based on direct anatomic visualization of the metastatic sites on the skeleton and, therefore, are not able to detect metastasis in early stages of the disease. Various biomarkers have been developed and used as indicators of bone formation or resorption. Substantially, these biochemical markers are products, released during the bone metabolic cycle and can be detected in biological samples. The levels of these markers in serum or urine can be correlated with the diagnosis of osseous metastases and the bulk of tumor burden and, in addition, may provide useful data for the patients follow-up, in order to evaluate the response to various treatments. The biochemical markers often used for monitoring bone formation involve total and bone-specific alkaline phosphatase, osteocalcin and procollagen type I extension propeptides, and those for bone resorption involve urinary calcium, hydroxyproline, hydroxylysine-glycosides, pyridinium crosslinks, crosslinked telopeptides of type I collagen, tartarate-resistant acid phosphatase and bone sialoprotein. For the treatment of bone disease, many therapies have been developed. Bisphosphonates, compounds based on a phosphorous-carbon-phosphorous spine similar to endogenous pyrophosphate, have been successfully used in the treatment of osteoporosis and hypercalcemia of malignancy. They have powerful anti-resorptive activity by suppressing the action of osteoclasts, resulting in the reduction of skeletal events. The analytical methods used for the determination of biomarkers in biological samples as well as the effect of bisphosphonates on the drift of metastatic bone disease are presented in this review.

Keywords: metastatic bone disease, skeletal metastases, biochemical markers, bisphosphonates

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