Elsevier

Bone

Volume 49, Issue 1, July 2011, Pages 71-76
Bone

Review
Bisphosphonates in oncology

https://doi.org/10.1016/j.bone.2011.02.003Get rights and content

Abstract

Bone metastases result in considerable morbidity, often affecting quality of life and independence over years, and may place complex demands on health care resources. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma and 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 has become increasingly important to prevent adverse effects of cancer treatments on bone health. These include chemotherapy induced ovarian failure and the use of aromatase inhibitors in breast cancer and androgen deprivation therapy in prostate cancer. Bisphosphonate strategies, similar to those used to treat post-menopausal osteoporosis, are the intervention of choice for patients with low bone mineral density or rapid bone loss, along with adequate calcium and vitamin D intake and a healthy lifestyle. There is a strong preclinical rationale for bisphosphonates to prevent metastasis, primarily through inhibition of the vicious cycle of metastasis within the microenvironment. Recent data suggest that adjuvant bisphosphonates, at least in some patient subgroups, may modify the course of the disease and disrupt the metastatic process, reducing the risks of disease recurrence.

In comparison to most other cancer treatments, adverse events related to bisphosphonate therapy are generally mild and infrequent; thus, the benefits of treatment within licensed indications will almost always outweigh the risks.

This article is part of a Special Issue entitled Bisphosphonates.

Research Highlights

► Bisphosphonates are an integral part of treatment for patients with bone metastases from solid tumours and in multiple myeloma.► Prevention of skeletal morbidity with bisphosphonates has transformed the quality of life of patients with bone metastases. ► Bisphosphonates prevent bone loss associated with cancer treatments. However, selection criteria for intervention require further definition. ► Adjuvant use of bisphosphonates in early breast cancer may modify the disease course.

Introduction

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 [1].

Metastatic bone disease disrupts the normal homeostasis of bone, and the resulting increased and imbalanced bone metabolism leads to a disturbance of bone integrity, which may result in skeletal morbidity. This includes bone pain, pathological fractures, a need for orthopaedic surgery to prevent or repair major structural damage, spinal cord and/or nerve root compression, and hypercalcaemia of malignancy. As indicated elsewhere in this special issue, it is now generally accepted that osteoclast activation is the key step in the establishment and growth of bone metastases. Biochemical data indicate that bone resorption is of importance not only in classic “lytic” diseases such as myeloma and breast cancer but also in prostate cancer [2]. As a result, the osteoclast is a key therapeutic target for skeletal metastases irrespective of the tissue of origin.

In addition to the effects of spread of cancer to bone, there may also be important effects of cancer treatments on bone health. This is largely mediated through the endocrine effects of treatments including ovarian suppression, chemotherapy induced menopause, androgen deprivation therapy and the use of aromatase inhibitors in postmenopausal women. The improvements in cancer survival that have been achieved over the past 30 years mean that the long-term effects of treatment on the skeleton are now an important clinical problem and may require therapeutic intervention with bone-targeted treatments [3].

Section snippets

Bisphosphonates to prevent skeletal morbidity and relief of bone pain

Bone pain may be severe in metastatic bone disease, necessitating opiate analgesics and palliative radiation therapy, and is often accompanied by a substantial decline in patient-reported quality of life. Despite the many advances in the treatment of advanced cancer over recent decades, skeletal morbidity remains a major clinical problem with annual fracture rates of 20–40% and the occurrence of a significant skeletal complication every 3–6 months in the absence of bone-targeted therapies such

Optimum use of bisphosphonates in metastatic bone disease

Despite the obvious clinical benefits of bisphosphonates, it is clear that only a proportion of events is prevented, and some patients do not experience a skeletal event despite the presence of metastatic bone disease. It is currently impossible to predict whether an individual patient needs or will benefit from a bisphosphonate. Criteria are needed as to when in the course of metastatic bone disease bisphosphonates should be started and stopped. Because of the logistics and cost of delivering

Bisphosphonates and cancer treatment-induced bone loss

Advances in treatments for breast and prostate cancer have improved long-term survival leading to an increasing awareness of potential detrimental effects of such therapies on bone health. Many of the therapeutic approaches used in breast or prostate cancer are associated with bone loss, which in turns leads to an increased risk of fracture [35], [36], [37]. The majority of patients being treated for breast or prostate cancer are not under the care of a bone specialist, and several guidance

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