Osteoporosis: now and the future

Lancet. 2011 Apr 9;377(9773):1276-87. doi: 10.1016/S0140-6736(10)62349-5. Epub 2011 Mar 28.

Abstract

Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This overview discusses these novel therapies and explains their underlying physiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Absorptiometry, Photon
  • Adaptor Proteins, Signal Transducing
  • Aged
  • Aged, 80 and over
  • Anabolic Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Benzodioxoles / therapeutic use
  • Biphenyl Compounds / therapeutic use
  • Bone Density / drug effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Morphogenetic Proteins / immunology
  • Bone Remodeling / drug effects*
  • Bone Resorption / drug therapy
  • Bone Resorption / metabolism
  • Calcium / metabolism
  • Denosumab
  • Diphosphonates / therapeutic use*
  • Female
  • Genetic Markers / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins / immunology
  • Middle Aged
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteoporosis / diagnosis
  • Osteoporosis / drug therapy*
  • Osteoporosis / etiology
  • Osteoporosis / metabolism*
  • Osteoporosis / prevention & control
  • Osteoporosis, Postmenopausal* / drug therapy
  • Osteoporosis, Postmenopausal* / metabolism
  • Osteoporotic Fractures / prevention & control*
  • Quinazolines / therapeutic use
  • RANK Ligand / therapeutic use
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / therapy
  • Wnt Proteins / drug effects
  • Wnt Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Anabolic Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Benzodioxoles
  • Biphenyl Compounds
  • Bone Density Conservation Agents
  • Bone Morphogenetic Proteins
  • DKK1 protein, human
  • Diphosphonates
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Quinazolines
  • RANK Ligand
  • SOST protein, human
  • Wnt Proteins
  • romosozumab
  • Denosumab
  • saracatinib
  • BHQ880
  • odanacatib
  • Calcium