title: Extrinsic mechanisms involved in age-related defective bone formation.
abstract: BACKGROUND
  Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify the mechanisms involved in the age-related defective bone formation.
  
  
  METHODS
  The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field.
  
  
  RESULTS
  Available basic and clinical studies indicate that multiple mechanisms are involved in the alterations of osteoblastogenesis and the resulting decline in bone formation with aging. Notably, the age-related osteoblast dysfunctions and defective bone formation are caused by a number of extrinsic clinical factors that inhibit anabolic signaling pathways in bone. Thus, targeting these pathways can abolish age-related bone loss.
  
  
  CONCLUSIONS
  The identification of extrinsic mechanisms involved in osteoblast dysfunctions associated with aging improves our knowledge of age-related bone loss and provides a basis for therapeutic intervention to improve bone formation and bone mass in the aging population.
authors.affiliation: Laboratory of Osteoblast Biology and Pathology, Institut National de la Santé et de la Recherche Médicale Unité 606, Paris F-75475, 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: D000368:Aged; D000375:Aging / Q000502:physiology; D000428:Alcohol Drinking / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000172:deficiency; D006801:Humans; D008297:Male; D009043:Motor Activity; D009752:Nutritional Status; D009929:Organ Size / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010024:Osteoporosis / Q000473:pathology*; D014029:Tobacco Use Disorder / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones