Effect of zoledronic acid on bone pain secondary to metastatic bone disease.

You are in your office. Mr.X, a 64 year-old patient well known to you for over 10 years, comes for persistent severe bone pain despite palliative radiotherapy and recent opioid treatment. Six years ago, he was diagnosed with stage IV prostate cancer with metastasis in the right pubic bone. He was treated with surgery and pelvic irradiation including the right pubis. One year prior to presentation he had an orchiectomy with prompt relief of pain and a decrease in his prostate specific antigen (PSA). He is taking morphine and dexamethasone was added recently with minimal effect. The pain has affected his sleep, appetite, and ability to enjoy life. He does not like the opiates’ effect on his ability to make high level decisions. The patient comes into the office noting that he just saw a commercial about a new medication, zoledronic acid, for treatment of cancer bone pain. He wants to know if this can help him. What are the current treatment options for metastatic bone disease? Bone metastases are frequent in patients with advanced cancer. The most common cancer which metastasize to bone are breast, lung, prostate, multiple myeloma, and renal. Skull, spinal column, rib cage, pelvis and femur are the most frequent sites of bone metastases. Pain from cancer is a major problem. Thirty percent of patients with cancer have pain at the time of diagnosis; 65 to 85% have pain when their disease is advanced. The impact of cancer pain is magnified by its interaction with other common cancer symptoms: fatigue, weakness, dyspnea, nausea, constipation, and impaired cognition. 18 With an integrated program of systemic, pharmacologic, and anticancer therapy, cancer pain can be effectively treated in 85-95% of patients. Many of the remaining patients can be helped by the use of invasive procedures. In the final days of life, pain not controlled by therapies aimed at both comfort and function can be relieved by intentional sedation. No patient with cancer needs to live or die with unrelieved pain. Pain caused by bone metastases lowers the quality of life and performance status of patients, and causes disability occurring at rest or typically during movement. 14 Treatment of bone metastases is aimed at reducing the risk of pathological fractures and other skeletal related events (SREs), as well as reducing pain to maximize patients’ quality of life. The options include surgery, radiation therapy, radiometabolic therapy, chemotherapy, hormone therapy, and other palliative treatment. Bisphosphonate therapy is now well established as a way of reducing morbidity from the lytic skeletal metastases. 19 BISPHOSPHONATES Metastatic bone disease is associated with a marked increase in bone resorption and formation rates, which can be evaluated by the measurement of biochemical markers of bone metabolism in the serum or urine. Bisphosphonates inhibit osteoclastic bone resorption and control bone metabolism via several mechanisms that differ from those of other antiresorptive agents. They contain 2 phosphate groups linked to 1 carbon atom, forming a stable structure (phosphorus-carbon-phosphorus) resistant to the action of osteoclastic hydrolytic enzymes. This backbone and the presence of R1 and R2 chains allow bisphosphonates to bind calcium phosphate and inhibit bone resorption by osteoclasts. 14 Bisphosphonates inhibit osteoclast maturation and function and ultimately cause osteoclast apoptosis. Initially bisphosphonates were developed to treat predominately osteolytic bone metastases. However histomorphometric and biochemical evidence show that osteoblastic lesions also lead to increased osteolysis and bone turnover and that bone resorption markers are significantly raised in patients with advanced prostate cancer. 14