title: Osteoblasts in osteoporosis: past, emerging, and future anabolic targets.
abstract: OBJECTIVE
  Age-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration.
  
  
  METHODS
  A limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010.
  
  
  CONCLUSIONS
  We present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.
authors.affiliation: Laboratory of Osteoblast Biology and Pathology, INSERM, U606, Hospital Lariboisiere, 2 Rue Ambroise Pare, 75475 Paris Cedex 10, France. pierre.marie@inserm.fr
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Marie
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000375:Aging / Q000502:physiology; D045930:Anabolic Agents / Q000627:therapeutic use; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D005260:Female; D005819:Genetic Markers / Q000187:drug effects; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000627:therapeutic use; D051153:Wnt Proteins / Q000187:drug effects / Q000502:physiology; D051176:beta Catenin / Q000187:drug effects / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D045930:Anabolic Agents; D019485:Bone Morphogenetic Proteins; C095550:CASR protein, human; D005819:Genetic Markers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; C422903:SOST protein, human; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone