Lyos

TEAM I

Epidemiological and Clinical Approaches of Bone Diseases

TEAM II

Fonctional Genomics and Treatment of Bone Metastases

TEAM III

Bone Quality and Biological Markers

INSERM UMR 1033,
Université de Lyon, France.

Lyos Team

Osteoporosis and bone metastasis induce structural alterations of the skeleton that lead to bone destruction and occurrence of pathological fractures. Despite of recent progress made to treat bone loss, there is clearly a need to better diagnose bone diseases and improve treatments of skeletal complications associated with bone diseases. For example, 50% of osteoporotic fractures occur in women whose bone mineral density is above the threshold described by the World Health Organization (WHO) as being associated with osteoporosis. Similarly, 70% of patients with advanced breast or prostate cancer have bone metastases. Yet, current treatments for skeletal lesions are only palliative.

 

Our project aims at developing a translational research from basic scientific discoveries into clinical improvements in diagnosis and treatments of bone diseases. Our scientific strategy hinges on 3 teams. Team 1 is doing clinical research. Epidemiological studies are conducted to identify determinants of bone loss for osteoporosis in women and men. Clinical trials are ongoing to study minimal residual disease in breast and prostate cancer, and to examine the therapeutic efficacy of a pharmacological inhibitor of bone resorption in the neoadjuvant treatment of locally advanced breast cancer. Team 2 aims at identifying and characterizing molecular mechanisms responsible for the tropism, osteomimetism and invasion of cancer cells in the bone marrow microenvironment. These studies build on clinical trials to detect and isolate cancer cells in the bone marrow. Additionally, new therapeutics are being tested in animal models of malignant bone diseases. Team 3 aims at studying mechanical determinants of bone quality in the clinic (osteoporosis) and in small animals (bone metastasis). Mechanisms of action of bone-targeted therapies are being tested on the determinants of bone quality. Finally, new biomarkers are developed to detect early bone metastasis formation.

Director: Philippe CLEZARDIN

 

 

Short description of the lab in figures:

 

  • Staff: 64
  • Basic and clinical scientists: 26
  • Technicians: 24
  • Postdoc and PhD students: 18
  • Industry partners: 5

 

6 key publications over the past 8 years:

 

  • SØRENSEN HT, CHRISTENSEN S, MEHNERT F, PEDERSEN L, CHAPURLAT RD, CUMMINGS SR, BARON JA. Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ. 2008 Apr 12;336(7648):813-6. Download PDF
  • CHAPURLAT RD, ARLOT M, BURT-PICHAT B, CHAVASSIEUX P, ROUX JP, PORTERO-MUZY N, DELMAS PD. Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study. J Bone Miner Res. 2007 Oct;22(10):1502-9. Download PDF
  • DAUBINÉ F, LE GALL C, GASSER J, GREEN J, CLÉZARDIN P. Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst 2007, 99:322-30. Download PDF
  • BOUCHARABA A, SERRE CM, GRES S, SAULNIER-BLACHE JS, BORDET JC, GUGLIELMI J, CLÉZARDIN P, and PEYRUCHAUD O. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J. Clin. Invest 2004, 114:1714-1725. Download PDF
  • CHAVASSIEUX P, SEEMAN E, DELMAS PD. Insights into material and structural basis of bone fragility from diseases associated with fractures : how determinants of the biomechanical properties of bone are compromised by disease. Endocrine Reviews 2007, 28: 151-164. Download PDF
  • BALA Y, DEPALLE B, FARLAY D, DOUILLARD T, MEILLE S, FOLLET H, CHAPURLAT R, CHEVALIER J, BOIVIN G. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res 2012, 27(4): 825-834\ Download PDF