The clinical use of bone resorption markers in patients with malignant bone disease

Coleman, Robert E.

doi:10.1002/cncr.10522

Cited by 87 publications

(45 citation statements)

References 72 publications

(140 reference statements)

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“…It indicates that this group had perhaps at first sight a poor prognostic. Similar results were previously shown in patients with breast cancer and bone metastases where elevated uNTx was predictive of disease extent [24], progression-free survival, and OS [16]. A number of prognostic analyses have been conducted in patients with CRPC [25][26][27][28], although there is currently no universally recognised prognostic index in these patients.…”

Section: Discussionsupporting

confidence: 61%

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Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

Rajpar¹,

Massard²,

Laplanche³

et al. 2010

Annals of Oncology

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Background: In patients with bone metastases from castration-resistant prostate cancer (CRPC) not pretreated with a bisphosphonate elevated N-telopeptide of type I collagen (uNTx), a marker of bone resorption, predicts skeletalrelated events (SRE). The aim of this study was to assess the prognostic value of uNTx for overall survival (OS) and the incidence of SRE in patients with bone metastases from CRPC receiving zoledronic acid.Methods: From 2004 to 2007, 94 patients with bone metastases from CRPC receiving zoledronic acid for at least 2 months were screened for uNTx.Results: Median age was 66 years (range 46-88). Median serum prostate-specific antigen (PSA) was 66 ng/ml (0-3984) and median uNTx was 19 nmol/mM creatinine (3-489). During follow-up, 38 patients (40%) experienced an SRE. Median OS was 20 months [95% (CI) confidence interval 15-24). In the multivariate analysis, elevated uNTx [hazard ratio (HR) 2.2 (95% CI 1.2-4.0)], serum PSA [HR 2.8 (95% CI 1.6-5.1)], and ECOG performance status were the only independent prognostic factors for OS. Median OS was 12 months (10-16) and 25 months (21-34) in patients with uNTx ‡20 nmol/mM creatinine and in those with uNTx <20 nmol/mM creatinine, respectively. Conclusion:An elevated uNTx level is an independent prognostic factor for OS in patients with bone metastases from CRPC receiving a bisphosphonate.

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Section: Discussionsupporting

confidence: 61%

“…Median OS was 20 months (95% CI [15][16][17][18][19][20][21][22][23][24]. In the univariate analysis, the factors associated with a favourable survival included uNTx <20 nmol/ml creatinine, a good PS (grade 0 or 1), serum PSA <70 ng/ml, haemoglobin >12 g/dl, and a normal alkaline phosphatase level (Table 2).…”

Section: Prognostic Factors For Survivalmentioning

confidence: 99%

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

Rajpar¹,

Massard²,

Laplanche³

et al. 2010

Annals of Oncology

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“…These growth factor and cytokine-mediated interactions lead to stimulation of osteoclastic bone resorption and both uncoupled and unbalanced bone remodeling (28). The effects of cancer on bone cell function can now be assessed accurately by the measurement of specific biochemical markers; for the assessment of bone resorption, these markers are derived from the breakdown of type I collagen, the main protein of bone (29). It is the result of this tumor-induced osteolysis and subsequent loss of the structural integrity of bone that may lead to bone pain, fractures, and other important skeletal complications, rather than stimulation of osteoblastic new bone formation.…”

Section: Use Of Bone Biochemical Markers To Predict Skeletal Morbiditmentioning

confidence: 99%

Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity

Coleman

2006

Clinical Cancer Research

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1,467

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The skeleton is the most common organ to be affected by metastatic cancer and the site of disease that produces the greatest morbidity. Skeletal morbidity includes pain that requires radiotherapy, hypercalcemia, pathologic fracture, and spinal cord or nerve root compression. From randomized trials in advanced cancer, it can be seen that one of these major skeletal events occurs on average every 3 to 6 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment. The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Additionally, the presence of extraosseous disease and the extent and tempo of the bone disease are powerful predictors of outcome. The latter is best estimated by measurement of bone-specific markers, and recent studies have shown a strong correlation between the rate of bone resorption and clinical outcome, both in terms of skeletal morbidity and progression of the underlying disease or death. Our improved understanding of prognostic and predictive factors may enable delivery of a more personalized treatment for the individual patient and a more cost-effective use of health care resources. Incidence of Bone MetastasesBone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers because of the prevalence of these diseases. At postmortem examination, f70% of patients dying of these cancers have evidence of metastatic bone disease (Table 1; ref. 1). However, bone metastases may complicate a wide range of malignancies, resulting in considerable morbidity and complex demands on health care resources. Carcinomas of the thyroid, kidney, and bronchus also commonly give rise to bone metastases, with an incidence at postmortem examination of 30% to 40%. However, tumors of the gastrointestinal tract rarely (<10%) produce bone metastases. Distribution of Bone MetastasesBone metastases most commonly affect the axial skeleton. The axial skeleton contains the red marrow in the adult, which suggests that properties of the circulation, cells, and extracellular matrix within this region could assist in the formation of bone metastases. Evidence exists that blood from some anatomic sites may drain directly into the axial skeleton. In postmortem studies of animals and humans, Batson (2) showed that venous blood from the breasts and pelvis flowed not only into the venae cavae but also into a vertebral-venous plexus of vessels that extended from the pelvis throughout the epidural and perivertebral veins. The drainage of blood to the skeleton via the vertebral-venous plexus may, at least in part, explain the tendency of breast and prostate cancers, as well as those arising in kidney, thyroid, and lung, to produce metastases in the axial s...

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“…Bisphosphonates inhibit osteoclast-mediated osteolysis and reduce bone marker levels (8,9). Zoledronic acid (ZOL) Validity of bone marker measurements for monitoring response to bisphosphonate therapy with zoledronic acid in metastatic breast cancer reduces the risk of skeletal-related events and suppresses levels of bone turnover markers in patients with multiple myeloma or bone metastases from solid tumors, including breast cancer (10,11).…”

Section: Introductionmentioning

confidence: 99%

Validity of bone marker measurements for monitoring response to bisphosphonate therapy with zoledronic acid in metastatic breast cancer

et al. 2013

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Abstract. Bone is the most common site of metastasis in breast cancer. Detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are non-invasive, inexpensive and may potentially serve as predictive and prognostic surrogate endpoints in detecting bone metastases and response to bisphosphonates. This study analyzed the value of the serum bone turnover markers PINP and ICTP for bone metastases in metastatic breast cancer patients receiving zoledronic acid. The results were compared with the serum levels of CEA and CA 15-3, and analyzed with respect to the number of bone metastases as well as clinical response. Forty patients with confirmed bone metastases who received chemotherapy and/or hormonal therapy and zoledronic acid i.v. q4 weeks participated in the present study. Blood (5 ml) was collected at the start of the study and q3 months for a period of one year for the analysis of PINP, ICTP, CEA and CA 15-3 using radioimmunoassays and ELISA, respectively. Imaging of bone metastases was performed at the same time points. In 29 out of 40 patients, more than 3 bone metastases were confirmed by imaging and 11 out of 40 patients presented with 3 or less. At the start of the study, the median value for ICTP was 6 µg/l and for PINP 58.7 µg/l. At the end of the study the median values were 4.5 µg/l for ICTP and 21 µg/l for PINP. When patients were stratified into responders and non-responders, a decrease in both PINP (P<0.0001) and ICTP (P=0.048) was observed for the responders, while the level of ICTP (P=0.02) increased for the non-responders. Serum PINP and ICTP concentrations were significantly different when patients were stratified into groups of those having more than 3 bone metastases and 3 or less, respectively (P<0.05). CEA and CA 15-3 levels did not differ with respect to the number of bone metastases, while the tumor marker levels determined at the end of the study significantly distinguished responders from non-responders (P=0.002 and P=0.004). In conclusion, in contrast to serum tumor markers, the determination of PINP and ICTP allows inferences to the number of bone metastases and appears to be a useful tool for prediction and monitoring metastatic breast cancer patients undergoing bisphosphonate therapy with zoledronic acid for the treatment of bone metastases.

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The clinical use of bone resorption markers in patients with malignant bone disease

Cited by 87 publications

References 72 publications

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity

Validity of bone marker measurements for monitoring response to bisphosphonate therapy with zoledronic acid in metastatic breast cancer

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