ECTS2016 Cancer and Bone Oral Communications Oral Communications (18 abstracts)
Anti-sclerostin treatment prevents multiple myeloma bone disease and reduces tumour burden
Michelle McDonald 1 , Michaela Reagan 2, , Rachael Terry 1 , Jessica Pettitt 1 , Lawrence Le 1 , Sindhu Mohanty 1 , Ina Kramer 4 , Michaela Kneissel 4 , Daniel Brooks 5 , Tegan Cheng 6 , David Little 6 , Mary Bouxsein 5 , Cliff Rosen 2 , Irene Ghobrial 3 & Peter Croucher 1
1The Garvan Institute of Medical Research, Syndey, NSW, Australia; 2Maine Medical Center Research Institutte, Scarborough, ME, USA; 3Dana Faber Cancer Institute, Harvard Medical School, Boston, MA, USA; 4Novartis Institute for BioMedical research, Basel, Switzerland; 5Beth Israel Deaconess Medical Center, Boston, MA, USA; 6Centre for Children’s Bone and Musculoskeletal Health, The Children’s Hospital at Westmead, Sydney, NSW, Australia.
Multiple myeloma is characterized by extensive bone marrow tumour and destructive osteolytic lesions. Both increased bone resorption and suppressed bone formation result in lesions and pathological fractures. Anti-resorptive therapies prevent further bone loss but patients continue to fracture, arguing for new therapies which increase bone strength. Anti-Sclerostin (Anti-Scl) is a potent stimulator of bone formation, is currently in clinical trials for osteoporosis, however it is yet to be explored in the setting of myeloma. We demonstrate that Anti-Scl (100 mg/kg weekly i.v.) prevents bone loss, increases bone strength and suppresses myeloma growth in murine myeloma. MicroCT analysis demonstrated a 29% loss in trabecular bone volume ratio (TbBV/TV) and 15% loss in cortical bone volume (CtBV) in vertebrae of mice bearing 5TGM1/eGFP murine myeloma cells (P<0.01). This loss in bone structure led to a 34% reduction in vertebral peak load under compression (P<0.01). Anti-Scl treatment prevented the structural bone loss seen in 5TGM1 burdened mice, increasing TbBV/TV by 29% and CtBV by 18%, thereby increasing vertebral peak load by 47% (P<0.01). Anti-Scl treatment did not alter tumour burden in the 5TGM1 model, whereas, in the human MM1S xenograft model, it suppressed tumour growth (P<0.05). Our results show that Anti-Scl treatment prevented the development of myeloma bone disease, improving bone microarchitecture and bone strength. This demonstrates the potential for Anti-Scl treatment in addressing bone loss and fractures in patients with myeloma. Furthermore, suppression of tumour growth with Anti-Scl treatment suggests a dual action for this agent in myeloma, limiting tumour growth whilst improving skeletal integrity.
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Bone Abstracts
ISSN 2052-1219 (online)
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