Bisphosphonates: Clinical Experience

Abstract

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletalrelated event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. 2004;9(suppl 4):14-27

The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo

“…Bisphosphonates, such as zoledronic acid, are in use as effective therapeutic agents for diseases characterized by aberrantly increased bone resorption, including osteoporosis, Paget disease, osteogenesis imperfecta, and bone metastatic tumors in breast cancer, prostate cancer, and multiple myeloma. (57,58) The similarities in the effects of dasatinib and zoledronic acid on trabecular bone architecture observed in this study suggest that dasatinib may be an effective treatment for diseases characterized by increased OC activity.…”

Skeletal-Related Events among Breast and Prostate Cancer Patients: Towards New Treatment Initiation in Malaysia's Hospital Setting

“…SRE is a term used in majority clinical trial, for instance it is used in investigating benefit of a conventional treatment of prevention of skeletal complications secondary to bone metastases, which is Bisphosphonate therapy (Coleman, 2004). Typically SRE includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and hypercalcemia of malignancy (HCM).…”

“…Bone metastases become clinically importance in breast and prostate cancers partly contributed by the reason of prevalence of these diseases. The prevalence of skeletal disease is greatest in breast and prostate carcinoma (Coleman, 2006) because patients with these cancers have a relatively long median survival time after diagnosis of bone metastases (Coleman, 2004). For instance, about 65.0% to 75.0% of patients with metastatic breast cancer or prostate cancer will develop skeletal metastases (Coleman, 1997).…”

“…Metastatic bone disease is a more frequent cause of malignancy and morbidity in skeleton than primary bone cancer (Bagi, 2005). Bone metastasis is a lesion that weakens the bone structure, causing a range of symptoms and complications, including skeletal complications that are known as skeletal-related events (SREs) (Coleman, 2004). Metastatic bone disease indicates the cancer disease progression and appears to be more resistant to treatment than visceral metastases (Bagi, 2005).…”

Optimizing Bisphosphonate Therapy in Oncology

“…In his review, Dr. Coleman discusses how a number of bisphosphonates, including zoledronic acid, reduce the incidence of skeletal complications in patients with breast cancer and indicates that zoledronic acid has demonstrated broad clinical activity in patients with a wide variety of tumor types including prostate cancer, lung cancer, and renal cell carcinoma. In addition to the clinical benefits of bisphosphonate therapy, Dr. Coleman discusses the various end points used in clinical trials of bisphosphonates and their relative merits [1].…”