Markers of bone turnover in prostate cancer

Prostate cancer is the most common malignancy in elderly men and is often a ssociated with bone metastases. Although bone metastases are osteosclerotic , histological and biochemical studies clearly indicate an increase of both bone formation and bone resorption, providing the rational for using bisph osphonate as a palliative treatment in these patients. The recent developme nt of specific and sensitive biochemical markers, reflecting the overall ra te of bone formation and bone resorption, has improved the non-invasive ass essment of bone turnover abnormalities in patients with prostate cancer: Th e immunoassays for bone-specific alkaline phosphatase and type I collagen p ropeptides are currently the most sensitive markers to assess bone. formati on. The best indices of bone resorption are the immunoassay for the pyridin oline cross-links and the related peptides that can be measured in urine an d more recently in serum. A better knowledge of the biochemistry, especiall y of the age-related post-translational modifications of type I collagen in the abnormal bone matrix, associated with bone metastases from prostate ca ncer may lead to markers of increased sensitivity. A recent example is the demonstration that the isomerization and racemization of the aspartic acid residue in C-telopeptides of type I collagen is impaired in patients with p rostate cancer and bone metastases, a pattern than can be detected with spe cific conformational antibodies. The most sensitive markers of bone formation and bone resorption are marked ly increased in patients with bone metastases compared with patients with c ancer but without metastases, the levels correlating with the extent of the bone involvement. However; their sensitivity remains limited, suggesting t hat the currently available biochemical markers cannot be used as a surroga te for bone scintigraphy in the diagnosis of bone involvement. A few studie s have suggested that the measurement of bone markers may be useful in the assessment of response to anti-endocrine therapy, although available data i ndicate a lower sensitivity than with prostates specific antigen. Additiona l longitudinal studies are required to assess the potential use of bone mar kers, especially to identify patients who relapse during the course of the treatment and, more specifically 3 those that result from the progression i n bone metastases. Clearly the established use of bone markers is for monitoring effects of bi sphosphonate treatment. Several studies have shown a rapid decrease of bone resorption markers in patients with prostate cancer and bone metastases, t he magnitude of the decrease correlating with the efficacy of the treatment in reducing bone pain. Thus, bone markers are likely to become a useful an d objective tool to monitor bisphosphonate treatment and individualie the t herapy scheme. (C) 2001 Harcourt Publishers Ltd.