Rationale for the use of bisphosphonates in osteoblastic and osteolytic bone lesions

Various primary malignancies develop bone metastases, and the resultant skeletal complications cause significant morbidity/mortality in advanced cancer patients. Bone lesions associated with metastases are traditionally classified radiologically as either osteolytic or osteoblastic, and both types of lesions are associated with elevated levels of specific bone resorption markers. Some common aspects in the pathophysiology of bone lesions have prompted speculation that treatments for osteolytic metastases might also be effective for predominantly osteoblastic metastases, such as in prostate cancer. Potent osteoclast activity inhibitors, bisphosphonates have been successful in the treatment of osteolytic tumor bone disease. Zoledronic acid is the first bisphosphonate shown to have a direct clinical benefit in the treatment of osteoblastic bone metastases, reducing the number and rate of skeletal events in prostate cancer patients with metastatic bone disease. Moreover, the shorter, more convenient infusion time and similar safety profile of 4 mg zoledronic acid compared with 90 mg pamidronate presently make zoledronic acid the preferred therapy for treatment of bone metastases in patients with all types of advanced malignancy.