**1. Introduction**

314 Prostate Cancer – Diagnostic and Therapeutic Advances

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patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural

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In western countries, prostate cancer is the most common non-dermatological malignant disease in men. An estimated 217730 new cases will have been diagnosed in 2010 in the USA (Jemal A et al., 2010) and 382250 cases were diagnosed in 2008 in Europe (Ferlay J et al., 2010), accounting for 28% and 22% of new non-cutaneous cancer diagnoses, respectively.

Bone is one of the most common sites of metastatic disease in patients with cancer, affecting approximately 400,000 patients each year. Nearly 70% of patients with advanced breast or prostate cancer will experience bone lesions; 50% of these patients will develop a secondary skeletal complications which represents a substantial disease and economic burden (Schulman KL & Kohles J, 2007).

The pathologic penetration of bone by tumour tissue can lead to numerous skeletal-related events, such as hypercalcemia, fracture, spinal cord compression, and potentially debilitating bone pain (Berruti A et al., 2002). Often these consequences result in the need for radiological and surgical intervention. Along with these therapies, pharmacological management is required to help reduce symptoms, prevent recurrence and further improve patients' quality of life.

Prostate carcinoma is the most common visceral malignancy and the second leading cause of death from cancer in men (Diamond T et al., 2004). Androgen-deprivation therapy (ADT), either alone (as depot gonadotrophin releasing hormone agonist) or in combination with antiandrogens (such as flutamide, bicalutamide, or cyproterone acetate), is recommended treatment for men with metastatic or locally advanced, non-metastatic prostate carcinoma (Fowler JE et al., 2002). Although it has been demonstrated that this form of therapy significantly reduces tumour growth and improves survival beyond 3 years after completion (Bolla M et al., 1997), there is growing concern regarding the negative effects of ADT on the skeleton. Accelerated bone loss, osteoporosis, and a potential for increased. Fracture rates have been reported in men with prostate carcinoma who are receiving ADT. Because many patients who present with prostate carcinoma are elderly and may have

Skeletal Related Events in Prostate Cancer: Important Therapeutic Considerations 317

In advanced prostate cancer, 65–75% of patients may eventually develop bone metastases. It is also important to note that approximately 10% of men with prostate cancer have bone metastases at initial presentation. Almost all patients who die of prostate cancer have bone

Men with prostate carcinoma who are treated with ADT are elderly and are at risk for a wide variety of metabolic bone problems. In a recent retrospective study of 125 men with a mean age of 77 years who were treated with ADT, Bruder and Welch reported a 27% prevalence of osteoporosis and a 51% prevalence of osteopenia (lumbar spine or femoral neck BMD T-score, -2.5 to -1.0) (Bruder JM & Welch MD, 2002); furthermore, 44% of the cohort had biochemical evidence of vitamin D insufficiency and secondary

Osteoporosis has become an increasingly important problem in men's health, accounting for significant morbidity in the aging male population. Patients with prostate cancer treated with ADT are at a high risk of osteoporosis. These patients may have additional morbidity from decreased bone mineralization, such as skeletal fractures. Moreover, a direct association has been noted between fractures and a decreased quality of life and increased

The prevalence of osteoporosis is lower in men than in women for several physiologic reasons, including a greater accumulation of skeletal mass during growth, greater bone size, absence of midlife menopause, a slower rate of bone loss, and a shorter male life expectancy (Amin S & Felson DT, 2001). The rates of annual bone mass loss in aging men range from 0.5% to 1% compared with 1% to 2% in women (Gilbert SM & Mckiernan JM, 2005; Smith MR, et al., 2001). The prevalence of osteoporosis increases progressively during ADT, reaching almost 50% after 4 years of ADT and more than 80% after 10 years. In contrast, it

In healthy adults, bone physiology is a dynamic, coordinated process controlled by 2 types of cells: osteoclasts and osteoblasts. Through a balanced remodeling process, osteoclasts resorb bone, and osteoblasts build bone at the same site (Coleman RE, 2001; Rosen LS, et al., 2003). This bone remodeling sequence consists of 4 distinct phases: activation, resorption,

Bone metastases are often characterized by their radiographic appearance as either osteolytic, osteoblastic, or mixed or mixed. Most patients with breast cancer have predominantly mixed or osteolytic lesions (Coleman RE, 2001; Rosen LS, et al., 2003). In contrast, patients with prostate cancer are often found to have predominantly osteoblastic lesions. However, regardless of appearance, there is significant osteolytic activity. In fact, osteolytic activity in these lesions often is comparable with, if not higher than, that typically seen in breast cancer and multiple myeloma. Such activity has been demonstrated by markedly elevated biochemical markers of bone resorption in the serum and urine of such patients. Only in multiple myeloma do purely lytic bone lesions develop (Coleman RE, 2001;

Several mechanisms have been proposed for metastatic spread to the bone. Early animal and human evaluations demonstrated that breast and pelvis tissue drain directly into the veins of the spine, increasing the deposition of metastatic cells into the bone marrow (Coleman

affects 35.4% of hormone-naive patients with prostate cancer (Morote J, et al., 2007).

**3. Bone health in prostate cancer** 

involvement (Greenspan SL, 2008).

mortality (Gilbert SM & Mckiernan JM, 2005).

**4. Mechanism of metastatic development** 

hyperparathyroidism.

reversal, and formation.

Rosen LS, et al., 2003).

preexisting osteoporosis, subclinical vitamin D deficiency, or any of a multitude of medical problems, the risk of skeletal deterioration is increased (Elliot ME et al., 2002).
