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Cancer-Associated Bone Disease

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Cancer-Associated Bone Disease Osteoporos Int DOI 10.1007/s00198-013-2530-3 POSITION PAPER Cancer-associated bone disease R. Rizzoli & J.-J. Body & M.-L. Brandi & J. Cannata-Andia & D. Chappard & A. El Maghraoui & C. C. Glüer & D. Kendler & N. Napoli & A. Papaioannou & D. D. Pierroz & M. Rahme & C. H. Van Poznak & T. J. de Villiers & G. El Hajj Fuleihan & for the International Osteoporosis Foundation Committee of Scientific Advisors Working Group on Cancer-Induced Bone Disease Received: 5 August 2013 /Accepted: 25 September 2013 # International Osteoporosis Foundation and National Osteoporosis Foundation 2013 Abstract Bone is commonly affected in cancer. Cancer- pathways, guidelines assist physicians in clinical decision- induced bone disease results from the primary disease, or making. Of the 57 million deaths in 2008 worldwide, from therapies against the primary condition, causing bone almost two thirds were due to non-communicable diseases, fragility. Bone-modifying agents, such as bisphosphonates led by cardiovascular diseases and cancers. Bone is a and denosumab, are efficacious in preventing and delaying commonly affected organ in cancer, and although the inci- cancer-related bone disease. With evidence-based care dence of metastatic bone disease is not well defined, it is This position paper has been endorsed by the Committee of Scientific Advisors of IOF R. Rizzoli (*) D. Kendler Division of Bone Diseases, Geneva University Hospitals and Faculty Department of Medicine, University of British Columbia, of Medicine, Geneva, Switzerland Vancouver, British Columbia, Canada e-mail: [email protected] N. Napoli J.<J. Body Division of Endocrinology, University Campus Bio-Medico, Rome, Department of Medicine, CHU Brugmann, Université Libre de Italy Bruxelles, Brussels, Belgium M.<L. Brandi A. Papaioannou Department of Internal Medicine, University of Florence, Florence, Department of Medicine, McMaster University, Hamilton, Ontario, Italy Canada J. Cannata-Andia D. D. Pierroz Bone and Mineral Research Unit, Instituto Reina Sofía, REDinREN, International Osteoporosis Foundation (IOF), Nyon, Switzerland ISCIII, Hospital Universario Central de Asturias, Universidad de Oviedo, Oviedo, Spain M. Rahme : G. El Hajj Fuleihan D. Chappard Calcium Metabolism and Osteoporosis Program, WHO GEROM-Research Group on Bone Remodeling and bioMaterials, Collaborating Center for Osteoporosis and Metabolic Bone LUNAM University, Angers, France Disorders, American University of Beirut Medical Center, Beirut, Lebanon A. El Maghraoui Rheumatology Department, Military Hospital Mohammed V, Rabat, C. H. Van Poznak Morocco University of Michigan, Ann Arbor, MI, USA C. C. Glüer Sektion Biomedizinische Bildgebung, Klinik für Diagnostische T. J. de Villiers Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Panorama MediClinic and Department of Gynaecology, Faculty of Germany Health Sciences, Stellenbosch University, Cape Town, South Africa Osteoporos Int estimated that around half of patients who die from cancer ET Endothelin in the USA each year have bone involvement. Furthermore, ESCEO European Society for Clinical and cancer-induced bone disease can result from the primary Economical Aspects of Osteoporosis disease itself, either due to circulating bone resorbing sub- and Osteoarthritis stances or metastatic bone disease, such as commonly FAC 5-Fluorouracil–doxorubicin– occurs with breast, lung and prostate cancer, or from ther- cyclophosphamide apies administered to treat the primary condition thus caus- FDG Fluorodeoxyglucose ing bone loss and fractures. Treatment-induced osteoporosis FGF Fibroblast growth factor may occur in the setting of glucocorticoid therapy or FRAX WHO fracture risk assessment tool oestrogen deprivation therapy, chemotherapy-induced ovar- GnRH Gonadotropin-releasing hormone ian failure and androgen deprivation therapy. Tumour HR Hazard ratio skeletal-related events include pathologic fractures, spinal IGF Insulin-like growth factor cord compression, surgery and radiotherapy to bone and IES Intergroup Exemestane Study may or may not include hypercalcaemia of malignancy IL Interleukin while skeletal complication refers to pain and other symp- IV Intravenous toms. Some evidence demonstrates the efficacy of various MRI Magnetic resonance imaging interventions including bone-modifying agents, such as NCCN National Comprehensive Cancer Network bisphosphonates and denosumab, in preventing or delaying NTX N-terminal telopeptide cancer-related bone disease. The latter includes treatment of ONJ Osteonecrosis of the jaw patients with metastatic skeletal lesions in general, adjuvant OPG Osteoprotegerin treatment of breast and prostate cancer in particular, and the PDGF-BB Platelet-derived growth factor-BB prevention of cancer-associated bone disease. This has led PET Positron emission tomography to the development of guidelines by several societies and PSA Prostate-specific antigen working groups to assist physicians in clinical decision PTHrP Parathyroid hormone-related protein making, providing them with evidence-based care pathways RANK Receptor activator of nuclear factor to prevent skeletal-related events and bone loss. The goal kappa-B of this paper is to put forth an IOF position paper address- RANKL Receptor activator of nuclear factor ing bone diseases and cancer and summarizing the position kappa-B ligand papers of other organizations. RCT Randomized controlled trial RR Relative risk Keywords Bone . Cancer . IOF . Skeletal-related events SABRE Study of Anastrozole with the Bis- phosphonate Risedronate Abbreviations SERM Selective oestrogen receptor modulator ABCSG Austrian Breast & Colorectal Cancer sFRP Secreted frizzled-related protein Study Group SRE Skeletal-related event ADT Androgen deprivation therapy TGF-β Transforming growth factor-beta AI Aromatase inhibitor TNF-α Tumour necrosis factor-alpha ALP Alkaline phosphatase TRAcP Tartrate-resistant acid phosphatase ASCO American Society of Clinical Oncology TSH Thyroid-stimulating hormone ATAC Arimidex, Tamoxifen Alone or in VEGF Vascular endothelial growth factor Combination VFA Vertebral fracture assessment AZURE Adjuvant Zoledronic Acid to Reduce WHO World Health Organization Recurrence Z-Fast and ZO-Fast Zometa-Femara Adjuvant Synergy Trials BTM Bone turnover marker αCTX Alpha cross-linked telopeptides type BMD Bone mineral density CI Confidence interval CMF Cyclophosphamide–methotrexate–5 fluorouracil Epidemiology of cancer-associated bone disease CT Computed tomography CTX Cross-linked terminal telopeptide Bone metastasis DKK1 Dickkopf-related protein DXA Dual-energy X-ray absorptiometry Cancer affects nearly 12.7 million people and is associated with ER Estrogen receptor over 7 million deaths in 2008 [1]. Cancer is a rising global Osteoporos Int health burden and it is estimated that in 2030, cancer deaths will survival rates in many types of cancer, early identification and be tallied at over 13 million (World Health Organization (WHO) treatment of osteoporosis among cancer patients could prevent 2010 Global Status Report [2]). Addressing the morbidity and unnecessary fractures, morbidity and reductions in quality of mortality of cancer is an important public health concern. On life. A recent prospective study in Germany of 1,041 cancer purpose, we are limiting our analysis to cancer bone involve- patients, mean age of 57 years, 78 % female, found elevated ment in adults and do not discuss cancer in children. rates of osteoporosis compared to the general population [10]. Metastases from cancer are associated with 90 % of cancer The prevalence of osteoporosis in both men and women with deaths [3]. It was estimated that one half of people who die from cancer in complete remission was 16 % (95 % confidence cancer in the USA have bone involvement [4–6]. Different interval (CI) 13.8–18.2) and osteopenia 44 % (defined using tumour types may have preferential sites of metastases; how- WHO criteria). Rates of osteoporosis were not statistically ever, the vast majority of tumours metastasize to bone, albeit at different among various cancer types, which included breast, varying frequencies. The term metastatic bone disease reflects gynaecological, prostate, colorectal and haematological can- the spread of a tumour to the bone. This term may be applied to cers, although sample size was too small to detect potential solid tumours, as well as to multiple myeloma, where the differences in rates between subtypes [10]. tumour is intrinsic to the bone marrow. In multiple myeloma, Women who have been treated medically for breast cancer 70–95 % of patients have tumour bone disease [7]. In breast may be at increased risk for bone loss and fractures [11, 12]. In cancer, bone is often the first site of distant metastases [5] with a case-controlled study of over 1,200 women with newly approximately one half of patients experiencing bone metasta- diagnosed breast cancer and no metastases, the annual inci- sesasthesiteoffirstrelapse[8]. In advanced breast or prostate dence of vertebral fractures was 2.72 % compared to 0.53 % in cancer, metastatic bone disease is present in the vast majority of the control arm, i.e. a fivefold increase, with rates adjusted for patients. Bone metastases may also be seen in 15–30 % of age, prevalent fractures and duration of follow-up [12]. Sim- cancers of the lung, gastrointestinal tract (colon and stomach) ilarly, in the prospective observational arm of the Women’s and the genitourinary (bladder, kidney and uterus) [9](Table1). Health Initiative, fracture rates in breast cancer
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