title: Dexamethsone suppresses bone formation via the osteoclast.
abstract: Glucocorticoids are central to treating inflammatory and immune disorders. These steroids, however, profoundly impact the skeleton, particularly when administered for prolonged periods. In fact, high-dose glucocorticoid therapy is almost universally associated with bone loss, prompting among the most common forms of crippling osteoporosis. Despite the frequency and severity of glucocorticoid-induced osteoporosis, its treatment is less than satisfactory, suggesting that its pathogenesis is incompletely understood. Net bone mass represents the relative activities of osteoblasts and osteoclasts and there is little question that glucocorticoids suppress the bone-forming cells, in vivo, via a process involving accelerated apoptosis (Weinstein 2001; Weinstein, Jilka, Parfitt, et al. 1998). Surprisingly, however, addition of glucocorticoids to cultures of osteoprogenitor cells actually increases their capacity to form mineralized bone nodules (Aubin 1999; Purpura, Aubin, and Zandstra 2004). This paradox raises the possibility that glucocorticoid suppression of bone formation, in vivo, reflects, at least in part, the steroid's targeting intermediary cells, which in turn inhibit the osteoblast. Bone remodeling is an ever-occuring event in mammals which is characterized by tethering of osteoclast and osteoblast function. The process is initiated by osteoclasts (OCs) resorbing a packet of bone, which in turn leads to osteoblasts being recruited to the site of resorption. This process establishes that osteoclastic bone resorption, in some manner, promotes osteoblastic bone formation at the same location. Consequently, pathologically or pharmacologically inhibited resorption eventuates in arrested osteoblast activity.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhao
authors.forename: Hideki
authors.initials: H
authors.lastname: Kitaura
authors.forename: Sandip
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Judson A
authors.initials: JA
authors.lastname: Brewer
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Muglia
authors.forename: F Patrick
authors.initials: FP
authors.lastname: Ross
authors.forename: Steven L
authors.initials: SL
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D001862:Bone Resorption; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D053245:RANK Ligand; D003907:Dexamethasone