Risks and benefits of bisphosphonates

Abstract

Bone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers due to the prevalence of these diseases. Bone metastases result in considerable morbidity and complex demands on health care resources, affecting quality of life and independence over years rather than months. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma as well as a wide range of solid tumours affecting bone by 30 -50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain. The use of bisphosphonates in early cancer is also increasingly important to prevent the adverse effects of cancer treatments on bone health. These include ovarian suppression and the use of aromatase inhibitors in breast cancer patients and androgen deprivation therapy in those with prostate cancer. Bisphosphonate strategies, similar to those used to treat postmenopausal osteoporosis, have suggested that bisphosphonates are a safe and effective treatment for the prevention of treatment-induced bone loss. When compared to other cancer therapies, the frequency and severity of adverse events related to bisphosphonate therapy are generally mild and infrequent; thus, the benefits of treatment with any bisphosphonate almost always outweigh the risks. However, renal dysfunction may occasionally occur and over recent years, a new entity, bisphosphonate-associated osteonecrosis of the jaw (ONJ), has been described. The incidence, clinical importance and prevention strategies to minimise the impact of this problem on patients requiring bisphosphonates is discussed. British Journal of Cancer (2008) Bone is a common site for metastasis in patients with solid tumours arising from the breast, prostate, lung, thyroid and kidney . Approximately 70% of patients with advanced prostate cancer or breast cancer and up to 40% of patients with other advanced solid tumours will develop bone metastases. Additionally, in more than 50% of men with advanced prostate cancer and around 20% of women with advanced breast cancer, metastatic disease appears clinically confined to the skeleton.Bone metastases are typically referred to as osteoblastic, osteolytic or mixed, based on the radiographic appearance of the lesions. However, osteoblastic and osteolytic bone lesions represent two extremes of a spectrum and osteoclast activity is increased in most bone metastases, including the typical osteoblastic metastases from prostate cancer (Coleman, 2006). Pathological activation of osteoclasts appears to play a central role in most disease-related skeletal complications and is, thus, a rational therapeutic target and the basis for the use of bisphosphonates across the range of cancers affecting bone (Dunstan et al, 2007).Metastatic bone disease disrupts the normal homeostasis of bone, a dynamic process that involves the coupled and balanced osteoclast-mediated osteolysis and osteogenesis by osteoblasts (Coleman, 2006). The re...

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors

“…38 Phase I/II trials 39 have shown that zoledronate, indicated for other human pathologies (eg. osteoporosis, multiple myeloma), 40 leads to significant IL-2-dependent gd T cell expansions, correlating to partial or complete clinical responses, thus indicating the feasibility and efficacy of this approach in some cancer patients. Preclinical approaches suggested that NBP-injection could be combined with Vg9Vd2 T cells administration in order to induce/enhance their antitumor reactivity.…”

Assessment of fracture risk in women with breast cancer using current vs emerging guidelines

“…Bisphosphonates have an established role in treating postmenopausal osteoporosis and have demonstrated clinical benefits for preventing bone loss during therapy for BC (Coleman, 2008;Hadji, 2009). The largest body of evidence to date is for twice-yearly intravenous zoledronic acid (4 mg), which can prevent bone loss and improve BMD in premenopausal and postmenopausal women receiving adjuvant endocrine therapy for BC (total N ¼ 2598) (Schenk et al, 2007;Brufsky et al, 2008;Gnant et al, 2008).…”

Numb chin syndrome: a case series and discussion

“…4,[6][7][8][9] Bisphosphonates are increasingly used in cancer therapy to protect the bone from destruction by metastatic tumour deposits, and from the effects of cancer therapeutics. 10 There are reports in the literature where NCS has occurred secondary to demyelinating or infl ammatory causes like multiple sclerosis and vasculitis. 11 In spite of its sinister connotation, dental causes are by far the commonest reasons for its occurrence.…”