title: Age-related changes in marmoset trabecular and cortical bone and response to alendronate therapy resemble human bone physiology and architecture.
abstract: In older humans, bone elongation ceases, periosteal expansion continues, and bone remodeling remains a dominant metabolic process. An appropriate animal model of type I and type II osteoporosis would be a species with sealed growth plates and persistence of bone remodeling. The rat is commonly used as a primary model, but due to delayed epiphyseal closure with continuous modeling and lack of Haversian remodeling, Food and Drug Administration guidelines recommend assessment of bone quality in an additional, non rodent, remodeling species. This study investigated the skeletal characteristics of senescent marmosets to evaluate their suitability as an osteoporosis model. Animals were randomized across three experimental groups; controls for both sexes and marmosets receiving alendronate for either 30 or 60 days (28 microg/kg, sc, twice per week). Outcome measures included serum chemistry and bone biomarkers, DEXA, histomorphometry, micro-computed tomography, and histopathology. Results showed that the adult marmoset skeleton has similar anatomical characteristics to the adult human, including the absence of growth plates, presence of Haversian system, and true remodeling of cancellous and cortical bone. Structural analyses of senescent marmoset cancellous bone demonstrated loss of trabecular mass and architecture similar to skeletal changes described for elderly men and women. Treatment with alendronate improved trabecular volume and number by reducing bone resorption, although bone formation was also reduced through coupling of bone remodeling. The common marmoset may provide a valuable model for research paradigms targeting human bone pathology and osteoporosis due to skeletal features that are similar to age-related changes and response to bisphosphonate therapy reported for humans.
authors.affiliation: Comparative Medicine, PGRD, Pfizer Inc., Groton, Connecticut 06340, USA. cedo.bagi@pfizer.com
authors.forename: Cedo M
authors.initials: CM
authors.lastname: Bagi
authors.forename: Marlo
authors.initials: M
authors.lastname: Volberg
authors.forename: Maria
authors.initials: M
authors.lastname: Moalli
authors.forename: Victor
authors.initials: V
authors.lastname: Shen
authors.forename: Ellen
authors.initials: E
authors.lastname: Olson
authors.forename: Nels
authors.initials: N
authors.lastname: Hanson
authors.forename: Edwin
authors.initials: E
authors.lastname: Berryman
authors.forename: Catharine J
authors.initials: CJ
authors.lastname: Andresen
mesh_terms: D015502:Absorptiometry, Photon; D000375:Aging / Q000473:pathology / Q000502:physiology*; D019386:Alendronate / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D002144:Callithrix / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D010758:Phosphorus / Q000097:blood
chemical_list: D050071:Bone Density Conservation Agents; D010758:Phosphorus; D002118:Calcium; D019386:Alendronate