Incidence of Skeletal Complications in Patients With Bone Metastatic Prostate Cancer and Hormone Refractory Disease: Predictive Role of Bone Resorption and Formation Markers Evaluated at Baseline

Berruti, Alfredo; Dogliotti, Luigi; Bitossi, Raffaella; Fasolis, Giuseppe; Gorzegno, G.; Bellina, M.; Torta, M.; Porpiglia, Francesco; Fontana, Dario; Angeli, Alberto

doi:10.1097/00005392-200010000-00024

Cited by 39 publications

(56 citation statements)

References 26 publications

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“…3,4,8 Hypercalcemia in malignancy is mainly due to the tumor production of PTHrP. 9 We disclose the limit of not having measured PTHrP but the low PTH levels observed in our hypercalcemic patients are consistent with PTHrP elevation since the IRMA assay we used for PTH evaluation does not cross-react with PTHrP.…”

Section: Discussionmentioning

confidence: 70%

“…Baseline bone pain was evaluated using a validated pain questionnaire, as previously reported. 8 Items included PS, analgesic consumption and mobility, as measured on a pain score of 0-19. All patients subsequently received second-line treatments consisting of endocrine therapy, chemotherapy, radiotherapy and radionuclide therapy, as indicated in association with the best palliative care.…”

Section: Patientsmentioning

confidence: 99%

“…3 Until the disease is responsive to androgen deprivation, adverse skeletal events and metabolic disturbances are rare. 8 However, they are more frequent when the tumor become refractory to hormone manipulations. 8 Calcium homeostasis is a tightly regulated process involving the coordinated efforts of the skeleton, kidney, parathyroid glands and intestine.…”

Section: Introductionmentioning

confidence: 99%

“…8 However, they are more frequent when the tumor become refractory to hormone manipulations. 8 Calcium homeostasis is a tightly regulated process involving the coordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Cancer cells adversely affect mineral metabolism through a broad spectrum of mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Tucci

Mosca

Lamanna

et al. 2008

Prostate Cancer Prostatic Dis

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Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n ¼ 51) had higher tumor load in bone (P ¼ 0.005), higher plasma chromogranin A (CgA, P ¼ 0.01), serum alkaline phosphatase (P ¼ 0.01), urinary N-telopeptide (NTX, P ¼ 0.002) and lower hemoglobin values (P ¼ 0.01), while hypercalcemic patients (n ¼ 16) had higher plasma CgA (P ¼ 0.001) and serum lactate dehydrogenase values (P ¼ 0.001), higher bone pain (P ¼ 0.003) and a lower frequency of pure osteoblastic lesions (P ¼ 0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P ¼ 0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P ¼ 0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.

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Section: Discussionmentioning

confidence: 70%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Tucci

Mosca

Lamanna

et al. 2008

Prostate Cancer Prostatic Dis

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“…5 Patients with hormone-refractory metastatic prostate cancer are particularly prone to incapacitating progressive bone disease. 6 The normal resculpturing of bone is governed by the coupled processes of bone resorption and formation. Modelling occurs in localised areas of cortical and trabecular bone known as bone metabolic units.…”

mentioning

confidence: 99%

Advances in the use of bisphosphonates in the prostate cancer setting

Coxon

Oades

Colston

et al. 2004

Prostate Cancer Prostatic Dis

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Prostate cancer incidence is rising, and represents a major public health issue. Bone is by far the most common site for metastases in this disease, accounting for considerable morbidity. Until recently, there have been few viable options for the treatment of patients with hormone-refractory metastatic disease. This review examines the pathophysiology underlying the development of bone metastases. It also summarises some of the clinical approaches for the management of this common condition, focusing on recent evidence supporting the use of zoledronic acid, a member of one of the most promising groups of pharmacological agents, the third-generation bisphosphonates. Aetiology and impact of prostate cancer-related bone metastasesProstate cancer is the most commonly diagnosed malignancy in males in the UK, with nearly 25 000 cases being reported in 1999 (www. cancerresearchuk.org/statistics). Prostate cancer-related morbidity and mortality are closely associated with the formation of metastases. Bone is the preferred site for these metastases, and estimates indicate that bone metastases are present in more than 80% of men with advanced prostate cancer. 1,2 A UK study has shown that bone metastases are present in up to 50% of men at the time of first presentation. 3 Considerable morbidity arises from various complications from bone metastases, and it is estimated that the average frequency of a 'skeletal-related event' in patients with bone metastases is 3-4 months, with these events invariably leading to a reduced quality of life. 4 Common presentations include pain, spinal cord compression, pathological fracture, and abnormalities in serum calcium levels. 5 Patients with hormone-refractory metastatic prostate cancer are particularly prone to incapacitating progressive bone disease. 6 The normal resculpturing of bone is governed by the coupled processes of bone resorption and formation. Modelling occurs in localised areas of cortical and trabecular bone known as bone metabolic units. Osteoclast-mediated resorption usually takes about 7-10 days, while the subsequent formation phase, governed by osteoblasts, lasts approximately 3 months (Figure 1). Local 'coupling' factors produced in the bone marrow regulate the remodelled bone. 7 The rich milieu of growth factors in the bone environment provides an attractive 'soil' for the seeding of certain tumour cells. In the presence of such cells, factors from tumour-induced breakdown of bone stimulate growth of further cancer cells, which in turn leads to further increases in bone resorption (Figure 2). This has been described as the vicious cycle. 7 As an example, tumour cells have been shown to release PTHrP, which stimulates osteoclastic resorption, via messaging from the osteoblast. 8 The resultant osteolysis releases several bone-derived growth factors, such as TGFb. Normally, TGFb serves to limit bone resorption via a negative feedback mechanism, but in the bone metastasis, TGFb stimulates invading tumour cells, partly accounting for this vicious cycle. 9 Prostate can...

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Low bone mineral density in hormone-na�ve men with prostate carcinoma

Smith

McGovern

Fallon

et al. 2001

Cancer

126

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Incidence of Skeletal Complications in Patients With Bone Metastatic Prostate Cancer and Hormone Refractory Disease: Predictive Role of Bone Resorption and Formation Markers Evaluated at Baseline

Abstract: Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Cited by 39 publications

References 26 publications

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Advances in the use of bisphosphonates in the prostate cancer setting

Low bone mineral density in hormone-na�ve men with prostate carcinoma

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