title: Bone remodelling: its local regulation and the emergence of bone fragility.
abstract: Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.
authors.affiliation: University of Melbourne, Melbourne, Australia. jmartin@svi.edu.au
authors.forename: T John
authors.initials: TJ
authors.lastname: Martin
authors.forename: Ego
authors.initials: E
authors.lastname: Seeman
mesh_terms: D000367:Age Factors; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D012737:Sex Factors