The use of molecular markers of bone turnover in the management of patients with metastatic bone disease

Abstract

SummaryBiochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone-seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease.

The role of the bone microenvironment in skeletal metastasis

“…Clinical studies have reported that cancer patients with high levels of bone resorption at baseline or on treatment are at higher risk for adverse clinical outcomes, such as SREs or tumour progression [26] , [27] , [28] , [29] , [30] , [31] , [32] , [37] , [149] , [150] , [151] , [152] , [153] , [154] . In this context, it is interesting to note that calcium and/or vitamin D deficiency have their own and well established effects on bone turnover.…”

A short account of metastatic bone disease

“…With regard to bone formation markers, the level of bone-specific alkaline phosphatase is usually increased in advanced metastatic bone disease reflecting active repair in an osteolytic lesion, or the presence of an osteoblastic lesion [51]. Of the bone resorption markers, N-telopeptide of type 1 collagen correlates well with the presence and extent of bone metastases and with the prognosis and response to treatment [49].…”

Use of urinary markers in cancer setting: A literature review

“…Siebel later explained that the contradiction of conventional results were possibly due to the long-term variability of markers of bone turnover in patients with breast cancer [32] . In addition to the risk of attaining false positive results [33] , the variability of markers is another limitation that has prevented urinary markers from being routinely used in clinical practice for prognostic value. It also reveals the inconsistency in results that may arise from similar studies with different patient cohorts.…”