Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab

  title={Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab},
  author={D. Lacey and W. Boyle and W. Simonet and P. Kostenuik and W. Dougall and J. K. Sullivan and J. S. Mart{\'i}n and R. Dansey},
  journal={Nature Reviews Drug Discovery},
  • D. Lacey, W. Boyle, +5 authors R. Dansey
  • Published 2012
  • Medicine
  • Nature Reviews Drug Discovery
  • Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The… CONTINUE READING
    376 Citations

    Paper Mentions

    Denosumab is an antibody against receptor-activator of nuclear factor kappa-B ligand that prevents recruitment and differentiation of mature osteoclasts. Treatment markedly decrease… Expand
    Biology of the RANKL–RANK–OPG System in Immunity, Bone, and Beyond
    • 306
    • PDF
    RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives
    • 21
    RANKL Cytokine: From Pioneer of the Osteoimmunology Era to Cure for a Rare Disease
    • 21
    • PDF
    Role of RANKL/RANK in primary and secondary breast cancer.
    • 27
    The RANKL-RANK Axis: A Bone to Thymus Round Trip
    • 19
    • PDF
    CD39 Produced from Human GMSCs Regulates the Balance of Osteoclasts and Osteoblasts through the Wnt/β-Catenin Pathway in Osteoporosis.
    • 5
    Targeting RANKL in metastasis
    • 48
    • PDF


    Do RANKL inhibitors (denosumab) affect inflammation and immunity?
    • 113
    • PDF
    RANK/RANKL: Regulators of Immune Responses and Bone Physiology
    • 352
    RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism.
    • J. Li, I. Sarosi, +20 authors W. Boyle
    • Chemistry, Medicine
    • Proceedings of the National Academy of Sciences of the United States of America
    • 2000
    • 1,037
    • PDF
    Structural and Functional Insights of RANKL–RANK Interaction and Signaling
    • 80
    • PDF
    RANK ligand is a prerequisite for cancer‐associated osteolytic lesions
    • 133