Bisphosphonates In Prostate Cancer

Bisphosphonates are agents that selectively inhibit osteoclastic bone resorption in ways that currently are only partially understood. A direct cytotoxic effect on osteoclasts has been shown for clodronate, whereas aminobisphosphonates impede the attachment of osteoclasts to the bone surface and promote their apoptosis.101,102 Also, bisphosphonates induce the apoptosis of osteoblasts and might inhibit the attachment of tumor cells to bone matrix. These agents have been shown to reduce bone resorption due to malignancy, and to be useful for patients with hypercalcemia and bony pain due to bone metastasis.103

A synchronous increase in bone resorption in osteoblastic metastasis has recently come to light. More specific urine markers of bone resorption increase in patients with osteosclerotic prostate cancer metastasis.73-75 Moreover, histo-pathological investigations have demonstrated that the number of active osteoblasts and indices of bone resorption increase significantly at sites of skeletal bone metastasis from prostate cancer, indicating that bone resorption plays a crucial role in the appearance and growth of osteosclerotic lesions and that its inhibition at the level of tumor infiltration might inhibit the progression of metastasis.

The clinical usefulness of bisphosphonates has been examined in bone metastasis from prostate cancer, typically osteoblastic lesions,104'105 and with a relatively small number of patients, pamidronate has been shown to inhibit osteoblastic metastasis from prostate cancer.105 Bisphosphonate has a favorable effect on bone pain in patients with osteoblastic bone metastasis from prostate cancer possibly as a result of inhibition of bone absorption, which precedes the apposition of excess woven bone and the appearance of osteosclerotic skeletal lesions. Also, bisphosphonates might inhibit cancer cell growth by decreasing growth factors released from bone tissue induced by osteoclasts. Further investigation is needed, however, to determine whether bisphosphonates inhibit growth of cancer cells in bone and osteoblastic metastasis.

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Fig. 2.12. Positive staining rates for ETA (A) and ETB (B) in patients with prostate cancer. Pvalues were determined by %2 tests. *ETA vs. ETB/ P< 0.0001.

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Fig. 2.12. Positive staining rates for ETA (A) and ETB (B) in patients with prostate cancer. Pvalues were determined by %2 tests. *ETA vs. ETB/ P< 0.0001.

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