title: Investigational drugs for the treatment of osteoarthritis.
abstract: BACKGROUND
  Osteoarthritis (OA) is a common joint disease with multiple pathophysiological processes, affecting the whole joint. Current therapeutic options such as NSAIDs can provide a palliative effect on symptoms but have limited effect on disease progression. New drugs targeting OA structures may retard disease progression at an earlier stage and delay the need for joint replacement.
  
  
  METHODS
  Some drugs have entered into clinical trials and a few, such as strontium ranelate, do have improvements in both pain and structure changes. However, most of them have failed in clinical trials largely due to increased side effects or the failure to identify the right OA phenotype for the right drug in clinical design. This review describes various investigational drugs developed for the treatment of OA covering those at stages from preclinical experiments to early phase clinical trials. They include drugs for slowing cartilage degradation, regulating cartilage metabolism, targeting subchondral bone, controlling inflammation and relieving pain.
  
  
  CONCLUSIONS
  Treatment options for OA remain limited. However, with the emergence of sensitive tools to detect early disease progression and identification of different OA phenotypes, disease-modifying anti-OA drugs with increased benefit and reduced risks will become available for OA treatment in the near future.
authors.affiliation: a 1 The First Affiliated Hospital of Anhui Medical University, Arthritis Research Institute, Department of Rheumatology and Immunology , Hefei, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
authors.affiliation: a 1 The First Affiliated Hospital of Anhui Medical University, Arthritis Research Institute, Department of Rheumatology and Immunology , Hefei, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: b 2 University of Sydney, Kolling Institute, Institute of Bone and Joint Research, Royal North Shore Hospital, Rheumatology Department , Sydney, NSW, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: a 1 The First Affiliated Hospital of Anhui Medical University, Arthritis Research Institute, Department of Rheumatology and Immunology , Hefei, China.|c 3 University of Tasmania, Menzies Institute for Medical Research , Private Bag 23, Hobart, Tasmania 7000, Australia +61 3 62 26 77 30 ; +61 3 62 26 77 04 ; changhai.ding@utas.edu.au.
authors.forename: Changhai
authors.initials: C
authors.lastname: Ding
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D050071:Bone Density Conservation Agents; D015507:Drugs, Investigational; D013876:Thiophenes; C081587:strontium ranelate
keywords: ADAMTS; MMP inhibitors; calcitonin; fibroblast growth factor; inflammation; osteoarthritis; pain; subchondral bone; therapy