Christine P. King Jennifer P. Huynh


Introduction: Metastatic bone disease, the condition where tumor cells spread from their origin tissue to bone, is common for breast and prostate cancer. Two main hypotheses, referred to as Paget’s “seed and soil” theory and Ewing’s anatomical theory, describe the homing of cancer cells to the bone. When breast cancer becomes metastatic and the tumor spreads to the bone, skeletal-related events can occur. Many patients use bone-modifying agents such as bisphosphonates (BPs) to manage skeletal deterioration. Given the longstanding history of BPs, this review aims to evaluate the efficacy and side effects of oral versus intravenous BPs as adjuvant treatment options for patients with metastatic breast cancer.

Methods: Relevant literature was sourced through a search of the PubMed and Google Scholar databases, using established inclusion criteria for screening papers published between 1889 and the present.

Results: Currently, there are three generations of BPs. Literature on the different generations reports that studies mainly use first-generation BPs for Paget’s disease and there is no significant effect of first-generation BPs on breast cancer survival rate. Second-generation BPs showed effectiveness in prolonging the progression of bone metastasis and decreasing distant recurrences to the bone in breast cancer patients. In attempts to improve the health outcomes of BPs, researchers examined third-generation BPs and found that they decreased skeletal-related events and pain levels.

Discussion: Comparing oral to intravenous administration of BPs, both had overall similar effects in reducing skeletal complications; however, the side effects resulting from BP use vary depending on the route of administration. Patients administered intravenous BPs exhibit an acute phase response and renal complications, while oral BPs cause disruptions in the gastrointestinal tract. Cost-effectiveness varied by study depending on assumptions made in the analytic models.

Conclusion: This novel review investigates the development of each generation of BPs to compare the implications of oral and intravenous administration. By accounting for differences across the three generations, healthcare providers can make informed decisions about BPs and create treatment plans tailored to the individual patient. Future research may explore how preexisting risk factors contribute to the occurrence of adverse effects of BP use. 

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