Metabolic bone disease induced by prostate cancer: Rationale for the use of bisphosphonates

Purpose: Increasing evidences indicate that despite the osteoblastic nature of metastatic bone lesions due to prostate cancer osteolysis is a regular feature and may cause skeletal morbidity. This observation provides the rat ionale for the use of bisphosphonates for managing bone metastatic prostate cancer. Materials and Methods: We reviewed the literature on the mechanisms by whic h prostate cancer affects bone cell function and disrupts physiological bon e turnover. We also summarized the clinical results of bisphosphonate fbr t reating bone pain in patients with prostate cancer. Results: Metastatic prostate cancer in bone interferes with physiological b one remodeling by abnormal release of the hormones and paracrine factors ph ysiologically involved in the modulation of osteoblastic and osteoclastic a ctivity. Tumor induced bone formation and resorption develop within the sam e metastasis but excessive new bone is deposited away from bone resorption sites and does not contribute to bone strength. The increase in bone resorp tion may also be a generalized phenomenon that is most likely due to iatrog enic osteoporosis or related to hyperparathyroidism in response to the incr eased calcium demand. The bone resorption index in patients with bone metas tatic prostate cancer correlates with bone pain and is an independent predi ctor of adverse skeletal events. However, small clinical studies of the eff icacy of bisphosphonates for controlling bone pain in patients with prostat e cancer show contradictory results. Conclusions: Improved understanding of the pathophysiology of prostate canc er induced metabolic bone disease implies that bisphosphonates may have a r ole in the treatment of this disorder. This issue is being addressed by lar ge-scale ongoing randomized studies.