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Zoledronic acid in adjuvant treatment of early breast cancer
Bone 38 (2006) S65 – S87 www.elsevier.com/locate/bone
Clinical Abstracts 57 Bishosphonates inhibit bone resorption in multicentric reticulohistiocytosis I.E. Adamopoulos, B.P. Wordsworth, J.R. Edwards, D.J. Ferguson, N.A. Athanasou, R.G.G. Russell Institute of Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7LD Multicentric reticulohistiocytosis (MR) is a systemic disease of unknown cause characterised by the presence of a heavy macrophage infiltrate in skin and synovial tissues and the development of an erosive polyarthritis. The synovial fluid in MR is known to contain numerous mononuclear cells, which we characterised in this study and determined whether they contribute to the joint erosion by differentiating into osteoclasts. Synovial fluid mononuclear cells were isolated from the knee joint of a 44 year old male with MR. These cells were cultured for 14 days with various combinations of macrophage-colony stimulating factor (M-CSF), soluble receptor activator for nuclear factor nB ligand (RANKL), tumour-necrosis factor-a (TNFa), interleukin-1a (IL-1a), osteoprotegerin (OPG), and zoledronate. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and the extent of lacunar resorption. Most MR synovial fluid mononuclear cells expressed a macrophage phenotype (CD14+, CD68+, HLA-DR+, CD11b+). Extensive osteoclast formation and lacunar resorption was noted in MCSF/ RANKL-treated cell cultures. ELISA of MR synovial fluid showed that TNFa was increased and OPG was decreased compared with OA synovial fluid. Lacunar resorption was inhibited in cultures with zoledronate. Pamidronate treatment of the patient also reduced the number of synovial fluid macrophages and resulted in less osteoclast formation and lacunar resorption. MR synovial fluid contains numerous macrophages that differentiate into osteoclasts by the RANKL signalling pathway. Inhibitors of osteoclast formation and resorption activity are likely to prevent the severe joint destruction that commonly occurs in MR. doi:10.1016/j.bone.2006.01.003
58 Zoledronic acid in adjuvant treatment of early breast cancer B. Alonso a, R. Alema´n b, L.M. Rguez a, M. Llanos a, E. Rguez b, J. Cruz a, J. Oramas a, J.N. Batista a a Service of Medical Oncology, Santa Cruz de Tenerife b Internal Medicine, Santa Cruz de Tenerife Introduction: Adjuvant therapies have prolonged survival of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). There is and increased interest in the potencial rol of bisphosphonate drugs in preventing and treating chemotherapy-induced bone loss. Objective: We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before first cycle intravenous zoledronic acid. Patients and methods: We prospectively included 55 women with NMBC (stage I– III) referred to the Medical Oncology Service of University Hospital of Canary Islands between September 2003 and August 2005 (53.4 T 12 years; 38.2% premenopausal). We measured lumbar and hip BMD (g/cm2) at diagnosis and after chemotherapy. Before chemotherapy all patients received an intravenous bisphosphonate (zoledronic acid). Results: BMD after chemotherapy (n = 55) significantly increased trochanter (0.711 T 0; 0.722 T 0, P = 0.048) and femoral neck (0.803 T 0; 0.824 T 0, P = 0.007) areas, and remained stable lumbar, total hip, intertrochanter, and Wards triangle areas.
Lumbar BMD Femoral neck BMD Trochanter BMD Intertrochanter BMD Ward’s triangle BMD BMD total hip
Pretreatment
Postreatment
0.993 T 0.803 T 0.711 T 1.084 T 0.677 T 0.936 T
0.985 0.824 0.722 1.093 0.674 0.927
0.163 0.131 0.105 0.153 0.184 0.135
T T T T T T
0.169 0.125 0.102 0.150 0.158 0.172
P NS 0.007 0.048 NS NS NS
Conclusion: Intravenous bisphosphonate (zoledronic acid) in our study have demostrate a benefit in reducing the loss bone mineral density after chemotherapy in women with NMBC. doi:10.1016/j.bone.2006.01.004
Clinical Abstracts 57 Bishosphonates inhibit bone resorption in multicentric reticulohistiocytosis I.E. Adamopoulos, B.P. Wordsworth, J.R. Edwards, D.J. Ferguson, N.A. Athanasou, R.G.G. Russell Institute of Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7LD Multicentric reticulohistiocytosis (MR) is a systemic disease of unknown cause characterised by the presence of a heavy macrophage infiltrate in skin and synovial tissues and the development of an erosive polyarthritis. The synovial fluid in MR is known to contain numerous mononuclear cells, which we characterised in this study and determined whether they contribute to the joint erosion by differentiating into osteoclasts. Synovial fluid mononuclear cells were isolated from the knee joint of a 44 year old male with MR. These cells were cultured for 14 days with various combinations of macrophage-colony stimulating factor (M-CSF), soluble receptor activator for nuclear factor nB ligand (RANKL), tumour-necrosis factor-a (TNFa), interleukin-1a (IL-1a), osteoprotegerin (OPG), and zoledronate. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and the extent of lacunar resorption. Most MR synovial fluid mononuclear cells expressed a macrophage phenotype (CD14+, CD68+, HLA-DR+, CD11b+). Extensive osteoclast formation and lacunar resorption was noted in MCSF/ RANKL-treated cell cultures. ELISA of MR synovial fluid showed that TNFa was increased and OPG was decreased compared with OA synovial fluid. Lacunar resorption was inhibited in cultures with zoledronate. Pamidronate treatment of the patient also reduced the number of synovial fluid macrophages and resulted in less osteoclast formation and lacunar resorption. MR synovial fluid contains numerous macrophages that differentiate into osteoclasts by the RANKL signalling pathway. Inhibitors of osteoclast formation and resorption activity are likely to prevent the severe joint destruction that commonly occurs in MR. doi:10.1016/j.bone.2006.01.003
58 Zoledronic acid in adjuvant treatment of early breast cancer B. Alonso a, R. Alema´n b, L.M. Rguez a, M. Llanos a, E. Rguez b, J. Cruz a, J. Oramas a, J.N. Batista a a Service of Medical Oncology, Santa Cruz de Tenerife b Internal Medicine, Santa Cruz de Tenerife Introduction: Adjuvant therapies have prolonged survival of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). There is and increased interest in the potencial rol of bisphosphonate drugs in preventing and treating chemotherapy-induced bone loss. Objective: We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before first cycle intravenous zoledronic acid. Patients and methods: We prospectively included 55 women with NMBC (stage I– III) referred to the Medical Oncology Service of University Hospital of Canary Islands between September 2003 and August 2005 (53.4 T 12 years; 38.2% premenopausal). We measured lumbar and hip BMD (g/cm2) at diagnosis and after chemotherapy. Before chemotherapy all patients received an intravenous bisphosphonate (zoledronic acid). Results: BMD after chemotherapy (n = 55) significantly increased trochanter (0.711 T 0; 0.722 T 0, P = 0.048) and femoral neck (0.803 T 0; 0.824 T 0, P = 0.007) areas, and remained stable lumbar, total hip, intertrochanter, and Wards triangle areas.
Lumbar BMD Femoral neck BMD Trochanter BMD Intertrochanter BMD Ward’s triangle BMD BMD total hip
Pretreatment
Postreatment
0.993 T 0.803 T 0.711 T 1.084 T 0.677 T 0.936 T
0.985 0.824 0.722 1.093 0.674 0.927
0.163 0.131 0.105 0.153 0.184 0.135
T T T T T T
0.169 0.125 0.102 0.150 0.158 0.172
P NS 0.007 0.048 NS NS NS
Conclusion: Intravenous bisphosphonate (zoledronic acid) in our study have demostrate a benefit in reducing the loss bone mineral density after chemotherapy in women with NMBC. doi:10.1016/j.bone.2006.01.004