Risks of therapy with bone antiresorptive agents in patients with advanced malignancy
- James R Berenson, MD
James R Berenson, MD
- Medical and Scientific Director
- Institute for Myeloma and Bone Cancer Research
- Alison T Stopeck, MD
Alison T Stopeck, MD
- Professor of Medicine
- Associate Director For Translational Research
- Stony Brook Cancer Center
- Section Editors
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
- Reed E Drews, MD
Reed E Drews, MD
- Section Editor — Complications of Cancer
- Associate Professor of Medicine
- Harvard Medical School
Parenteral administration of osteoclast inhibitors (bisphosphonates and denosumab) reduces the frequency of skeletal-related events among patients with multiple myeloma and in those with bone metastases from a variety of solid tumors, including breast, lung, and prostate cancer. Prolonged therapy with these antiresorptive agents in patients with advanced malignancy is generally well tolerated, but some side effects are potentially serious and require periodic monitoring [1-3].
This topic will provide an overview of the risks of therapy with antiresorptive agents in patients with skeletal involvement from advanced malignancy. The therapeutic use of bisphosphonates and denosumab in malignant disease, and their use and side effects in other conditions, such as osteoporosis and cancer treatment-related bone loss, are discussed separately, as is a more thorough discussion of medication-related osteonecrosis of the jaw (MRONJ). (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors" and "The use of bisphosphonates in patients with multiple myeloma" and "The use of bisphosphonates in postmenopausal women with osteoporosis" and "Denosumab for osteoporosis" and "Evaluation and management of aromatase inhibitor-induced bone loss" and "Overview of the use of osteoclast inhibitors in early breast cancer" and "Side effects of androgen deprivation therapy", section on 'Prevention' and "Bone metastases in advanced prostate cancer: Management" and "Medication-related osteonecrosis of the jaw in patients with cancer".)
CLASSES OF ANTIRESORPTIVE AGENTS
Two classes of antiresorptive agents are used for prevention of skeletal events in patients with advanced malignancy:
●Bisphosphonates pamidronate, zoledronic acid, and ibandronate are structural analogs of inorganic pyrophosphate. Pamidronate and zoledronic acid are approved in the United States, while ibandronate is approved in many European countries. Bisphosphonates inhibit osteoclastic bone resorption by attaching to hydroxyapatite binding sites within bone. The bisphosphonate that is released during bone resorption impairs the ability of the osteoclasts to adhere to the bony surface and resorb bone. In addition, bisphosphonates also reduce osteoclast activity by decreasing osteoclast progenitor development and recruitment, and by promoting osteoclast apoptosis. (See "Pharmacology of bisphosphonates".)
●Denosumab is a fully human monoclonal antibody that inhibits osteoclastic bone resorption by specifically binding and inhibiting the receptor activator of nuclear factor-KB ligand (RANKL), a key regulator of osteoclast formation, function, and survival. (See "Normal skeletal development and regulation of bone formation and resorption".)
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- CLASSES OF ANTIRESORPTIVE AGENTS
- RISKS SHARED BY BOTH CLASSES OF DRUGS
- Osteonecrosis of the jaw
- Hypocalcemia and other electrolyte abnormalities
- Atypical fractures
- RISKS SPECIFIC TO BISPHOSPHONATES
- Proteinuria and renal insufficiency
- - Incidence and risk factors
- Multiple myeloma
- Other malignancies
- - Management and prevention
- Acute phase response
- Ocular toxicities
- Bone, joint, or muscle pain
- Atrial fibrillation and stroke
- RISKS SPECIFIC TO DENOSUMAB
- Renal effects
- Neutralizing antibodies
- SUMMARY AND RECOMMENDATIONS