Collagenous and non-collagenous biochemical markers of bone metastases from prostate cancer.

The importance of the bone microenvironment to the pathophysiology and morbidity associated with prostate cancer bone metastasis is becoming increasingly apparent. Significant alterations take place in the microenvironment of bone, which disturb the normal coupling that exists between bone resorption and bone formation. Consequently, a better understanding of the mechanisms that interact at the molecular level will definitely result in more effective therapy for patients with this devastating complication of prostatic carcinoma. This review will discuss the diagnostic and predictive implications of various collagenous and non-collagenous bone markers, along with the novel markers of osteoclastogenesis and other matrix enzymes such as metalloproteinases and growth factors responsible for the complex biochemical mechanisms that upregulate bone resorption/formation during the development of metastasis. Further prospective studies are needed to determine whether any of these markers measured longitudinally in prostate cancer patients without bone scan evidence of skeletal disease will ultimately predict those patients who will develop bone metastases from their malignancy. Nonetheless, from the clinical point of view it is important to know that these novel markers carry the potential to provide meaningful information for daily practice by using upper normal reference values as cut-offs for identifying patients with an increased risk of developing progressive bone disease or skeletal related events.