Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Abstract

Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

Mechanisms of cancer metastasis to the bone

“…In prostate cancer patients with clinical osteoblastic lesions, blood and urinary levels of bone resorption markers are often elevated [48]. Clinical trials have suggested that blocking osteoclastic bone resorption reduces related skeletal events in prostate cancer patients [49].…”

Osteoporosis in men with prostate carcinoma receiving androgen‐deprivation therapy

“…An increase in markers of bone formation suggests the development of osteoblastic secondaries, whereas increases in markers of bone resorption suggest the development of lytic lesions. 43,44 These two processes frequently coexist in metastatic bone lesions. Bisphosphonate therapies have been shown to reduce markers of bone turnover and the number of skeletal-related events in individuals with metastatic prostate carcinoma.…”

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

“…25 Other bone markers, such as serum osteocalcin and serum type I procollagen Cpropeptide, are also indicators of osteoblast activity; nevertheless, none of these other markers are specific biomarkers for bone metastasis. 26,27 In the current study, higher miR-141 levels indicated a higher number of bone lesions, which suggests that we may be able to use serum miR-141 as a specific marker for bone metastasis.…”