title: Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.
abstract: Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.
authors.affiliation: Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu, Aichi, 474-8511, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fumoto
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D002452:Cell Count; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D005819:Genetic Markers; D007811:Lanthanum / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D010011:Osteocytes / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000503:physiopathology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat; C119467:lanthanum carbonate; D007811:Lanthanum; D000469:Alkaline Phosphatase