title: Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment.
abstract: Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansion. Both agents induced an expansion of the colony-forming unit-erythroid populations. However, unlike erythropoietin, darbepoietin-alfa did not impair bone marrow B lymphopoiesis. Strikingly the bone loss observed with erythropoietin was not apparent following darbepoietin-alfa treatment. This analysis demonstrates that whilst darbepoietin-alfa has similar in vivo erythropoietic potency to erythropoietin, it preserves the bone marrow microenvironment. Thus erythropoietin and darbepoietin-alfa manifest different action showing that erythropoiesis stimulating agents have differential non-erythroid effects dependent on their duration of action.
authors.affiliation: St Vincent’s Institute of Medical Research and Department of Medicine at St. Vincent’s Hospital, University of Melbourne, Fitzroy,Victoria, Australia.
authors.forename: Sita R
authors.initials: SR
authors.lastname: Dewamitta
authors.forename: Megan R
authors.initials: MR
authors.lastname: Russell
authors.forename: Harshal
authors.initials: H
authors.lastname: Nandurkar
authors.forename: Carl R
authors.initials: CR
authors.lastname: Walkley
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology*; D016723:Bone Remodeling / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects*; D000068256:Darbepoetin alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006397:Hematinics / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D038041:Lymphopoiesis / Q000187:drug effects; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa