Bisphosphonates (Cancer treatment)
Bisphosphonates are a class of medications primarily used to inhibit bone resorption, making them particularly relevant in the treatment of various bone-related conditions, including certain cancers. They are beneficial for patients with breast cancer, metastatic bone cancer, multiple myeloma, and those experiencing hypercalcemia of malignancy (HCM). By decreasing the activity of osteoclasts—cells that break down bone—bisphosphonates help reduce bone loss, alleviate pain from bone lesions, and lower the risk of fractures. They are also associated with a decreased incidence of bone metastases in breast cancer patients and may help lower the likelihood of breast cancer recurrence.
These drugs can be administered orally or intravenously, with the latter sometimes leading to side effects such as fever and local site reactions. Common side effects include gastrointestinal disturbances, renal impairment, and systemic symptoms like muscle pain and anxiety. Bisphosphonates are typically taken without food to enhance their effectiveness. Overall, they represent an important therapeutic option for managing bone health in cancer patients and mitigating some treatment-related risks.
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Bisphosphonates (Cancer treatment)
DEFINITION: Bisphosphonates are medications that act primarily on bone to inhibit resorption or bone destruction resulting from cell-induced bone breakdown. They treat various bone-degenerating conditions and may also be used to reduce the risk of recurrence or metastases in breast cancer patients.
ATC CODE: M05BA
Cancers treated:Breast cancer, hypercalcemia of malignancy (HCM), metastatic bone cancer, multiple myeloma, bone pain, osteoporotic bone loss from cancer treatments
Subclasses of this group: Aminobisphosphonates, nonaminobisphosphonates
Delivery routes: Bisphosphonates are administered as oral tablets and as intravenous (IV) solutions to outpatients and inpatients. Bisphosphonates in any form are best administered without food to avoid decreased bioavailability.
How these drugs work: Bone resorption is part of normal bone regeneration mediated by osteoclasts, or bone breakdown cells. Abnormal osteoclast activity results from lytic bone lesions of multiple myeloma, metastatic bone tumors from breast cancer or other solid tumors, or osteoporosis from glucocorticoids in chemotherapy regimens and from breast-cancer-induced menopause.
Bisphosphonates inhibit resorption by decreasing osteoclast activity. This mechanism reduces further bone loss and fracture, minimizes pain associated with osteoclast lesions and weakened bone, and reverses hypercalcemia of malignancy (HCM), or abnormally high blood calcium, which can result when bone breakdown releases calcium to the blood. Monthly bisphosphonate administration has been shown to reduce the incidence of bone metastases in women with breast cancer as well as metastases after ductal carcinoma in situ (DCIS). These drugs have also been shown to reduce the risk of breast cancer recurrence. Further, bisphosphonates have substantially reduced the risk of bone loss and fracture in spinal vertebrae and the hip.
Side effects: A major side effect of this drug class is irritation of the esophageal mucosa, which can be reduced by taking the drug with a full glass of water and by remaining in an upright position directly after drug ingestion. This side effect may occur even with IV administration.
Other side effects include constipation, diarrhea, dyspnea, myalgia, fever, decreased calcium and phosphate, and altered magnesium. Impaired kidney function and renal failure are possible. IV administration causes fever, flulike syndrome, and local injection site reactions. Other side effects noted in trials of patients with cancer include anxiety, headache, insomnia, anorexia, and abdominal pain.
Bibliography
Bartl, R. Bisphosphonates in Medical Practice: Actions, Side Effects, Indications, Strategies. Springer, 2007.
Brufsky, Adam M., et al. "Long-Term Treatment with Intravenous Bisphosphates in Metastatic Breast Cancer: A Retrospective." Breast Journal, vol. 19, no. 5, 2013, pp. 504–11.
Eisen, Andrea, et al. “Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer.” Journal of Clinical Oncology, vol. 40, no. 7, 2022, pp. 787-800, doi.org/10.1200/JCO.21.0264. Accessed 6 July 2024.
Mapes, Diane. “Risk vs. Benefit: Bisphosphonates in Breast Cancer.” Fred Hutchinson Cancer Center, 4 May 2021, www.fredhutch.org/en/news/center-news/2021/05/risk-vs-benefit-bisphosphonates-breast-cancer.html. Accessed 6 July 2024.
Suresh, Ernest, et al. "Safety Issues with Bisphosphonate Therapy for Osteoporosis." Rheumatology, vol. 53, no. 1, 2014, pp. 19–31.
Xue, Deting, et al. "Do Bisphosphonates Affect Bone Healing? A Meta-analysis of Randomized Controlled Trials." Journal of Orthopaedic Surgery and Research, vol. 9, no. 1, 2014, pp. 1–17.