Abstract
The survival prospects for many patients with cancer are steadily improving. As a result, survivorship issues are of increasing importance as attempts are made to minimize the long-term adverse effects of cancer treatments. Cancer therapies can adversely affect bone health, particularly in women with breast cancer and men with prostate cancer. Strategies for screening patients at increased risk for fragility fracture, and treatment algorithms using both bone-targeted treatments and other therapeutic interventions, are being developed. Both bisphosphonates and denosumab have been evaluated as treatments to prevent or reverse the bone loss associated with cancer treatments. Zoledronic acid is the most extensively assessed agent and has been shown to prevent bone loss in patients with breast cancer experiencing a premature menopause, in postmenopausal women receiving an aromatase inhibitor and in patients with prostate cancer undergoing androgen deprivation therapy (ADT). To date, the improvements in bone mineral density have not translated into a reduced fracture rate. However, in a large phase III trial, denosumab has been shown to reduce vertebral fractures in men receiving ADT for prostate cancer. These bone-targeted treatments have also been shown to modify the course of the underlying cancer and prevent metastasis, although the beneficial effects are confined to patients with low levels of circulating reproductive hormones.
Key Points
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The management of bone loss induced by cancer treatment has increased in importance as the survival prospects of patients with cancer have improved
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The abrupt reduction in the levels of circulating oestradiol associated with a range of cancer treatments results in rapid bone loss and an increased risk of fracture
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Bisphosphonates and denosumab can prevent bone loss and normalize bone turnover but, to date, only one trial with denosumab has shown a reduction in fracture incidence
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Further research is needed to refine a risk-adapted strategy for intervention based on the approaches used for the prevention and treatment of postmenopausal osteoporosis
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The disease-modifying effects of bone-targeted treatments provide an exciting opportunity for further improvements in cancer outcomes
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Acknowledgements
R. E. Coleman's work is funded in part by Yorkshire Cancer Research. E. Rathbone's work is supported by a Clinical Research Fellowship from Cancer Research UK. J. E. Brown's work is supported by a Clinician Scientist Grant from Cancer Research UK.
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All authors contributed equally to researching data for and writing the article; R. E. Coleman and J. E. Brown provided substantial contributions to discussion of content and reviewed/edited the manuscript before submission.
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R. E. Coleman has provided expert testimony for Novartis. J. E. Brown has acted as a consultant for Amgen, Bristol–Myers Squibb and Novartis, and has received speakers bureau (honoraria) from Amgen and Novartis. E. Rathbone declares no competing interests.
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Coleman, R., Rathbone, E. & Brown, J. Management of cancer treatment-induced bone loss. Nat Rev Rheumatol 9, 365–374 (2013). https://doi.org/10.1038/nrrheum.2013.36
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DOI: https://doi.org/10.1038/nrrheum.2013.36
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