Duration of bone protection by a single osteoprotegerin injection in rats with adjuvant-induced arthritis.
Daily osteoprotegerin (OPG) injection for 7 or more days prevents bone loss for 3 weeks in rats with adjuvant-induced arthritis (AdA). The present experiments defined the duration of bone protection in AdA provided by a single OPG bolus. Male Lewis rats received OPG at the onset or peak of clinical disease, after which bone mineral density (BMD), erosions, and osteoclasts were evaluated. An OPG bolus (4 mg/kg subcutaneously) at onset eliminated osteoclasts, preserved BMD for 7 days, and prevented bone erosions for 4 days. In contrast, an OPG bolus (1, 3, 10, or 30 mg/kg intravenously) given at the peak of disease eradicated osteoclasts in a dose-dependent manner but had no impact on bone integrity due to extensive pre-existing bone loss. These data indicate that one OPG injection will inhibit joint erosions for several days, and confirm that bone-sparing therapy must be initiated early in disease to protect joint integrity.
Bolon
B
B
Department of Pathology, Amgen, Thousand Oaks, California 91321-1799, USA.
Campagnuolo
G
G
Feige
U
U
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001169:Arthritis, Experimental / Q000188:drug therapy*; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use*; D006614:Hindlimb / Q000473:pathology; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D010010:Osteoclasts / Q000378:metabolism; D053244:Osteoprotegerin; D051381:Rats; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C506032:Tnfrsf11b protein, rat