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Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta
dc.contributor.authorSinder, Benjamin Pen_US
dc.contributor.authorEddy, Mary Men_US
dc.contributor.authorOminsky, Michael Sen_US
dc.contributor.authorCaird, Michelle Sen_US
dc.contributor.authorMarini, Joan Cen_US
dc.contributor.authorKozloff, Kenneth Men_US
dc.date.accessioned2013-01-03T19:41:55Z
dc.date.available2014-03-03T15:09:25Zen_US
dc.date.issued2013-01en_US
dc.identifier.citationSinder, Benjamin P; Eddy, Mary M; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M (2013). "Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta." Journal of Bone and Mineral Research 28(1): 73-80. <http://hdl.handle.net/2027.42/95242>en_US
dc.identifier.issn0884-0431en_US
dc.identifier.issn1523-4681en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/95242
dc.description.abstractOsteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long‐bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl‐Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl‐Ab therapy was investigated in mice heterozygous for a typical OI‐causing Gly→Cys substitution in col1a1 . Two weeks of Scl‐Ab successfully stimulated osteoblast bone formation in a knock‐in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long‐bone fragility. Image‐guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl‐Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short‐term Scl‐Ab was successfully anabolic in osteoblasts harboring a typical OI‐causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. © 2013 American Society for Bone and Mineral Researchen_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherCOLLAGENen_US
dc.subject.otherANABOLIC THERAPYen_US
dc.subject.otherOSTEOGENESIS IMPERFECTAen_US
dc.subject.otherSCLEROSTIN ANTIBODYen_US
dc.subject.otherBONE MASSen_US
dc.titleSclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfectaen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelInternal Medicine and Specialitiesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USAen_US
dc.contributor.affiliationumDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USAen_US
dc.contributor.affiliationotherDepartment of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA, USAen_US
dc.contributor.affiliationotherBone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USAen_US
dc.contributor.affiliationother2015 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109‐2200, USAen_US
dc.identifier.pmid22836659en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/95242/1/1717_ftp.pdf
dc.identifier.doi10.1002/jbmr.1717en_US
dc.identifier.sourceJournal of Bone and Mineral Researchen_US
dc.identifier.citedreferenceMarini JC, Hopkins E, Glorieux FH, Chrousos GP, Reynolds JC, Gundberg CM, Reing CM. Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. J Bone Miner Res. 2003; 18: 237 – 43.en_US
dc.identifier.citedreferencePadhi D, Jang G, Stouch B, Fang L, Posvar E. Single‐dose, placebo‐controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011; 26: 19 – 26.en_US
dc.identifier.citedreferencePoole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB.J. 2005; 19: 1842 – 4.en_US
dc.identifier.citedreferenceLi X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE. Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005; 280: 19883 – 7.en_US
dc.identifier.citedreferenceLeupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, Bouwmeester T, Schirle M, Bueno‐Lozano M, Fuentes FJ, Itin PH, Boudin E, de Freitas F, Jennes K, Brannetti B, Charara N, Ebersbach H, Geisse S, Lu CX, Bauer A, Van Hul W, Kneissel M. Bone overgrowth‐associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011; 286: 19489 – 500.en_US
dc.identifier.citedreferenceLi X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009; 24: 578 – 88.en_US
dc.identifier.citedreferenceForlino A, Porter FD, Lee EJ, Westphal H, Marini JC. Use of the Cre/lox recombination system to develop a non‐lethal knock‐in murine model for osteogenesis imperfecta with an α1(I) G349C substitution. J Biol Chem. 1999; 274: 37923 – 31.en_US
dc.identifier.citedreferenceKozloff KM, Carden A, Bergwitz C, Forlino A, Uveges TE, Morris MD, Marini JC, Goldstein SA. Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength. J Bone Miner Res. 2004; 19: 614 – 22.en_US
dc.identifier.citedreferenceUveges TE, Collin‐Osdoby P, Cabral WA, Ledgard F, Goldberg L, Bergwitz C, Forlino A, Osdoby P, Gronowicz GA, Marini JC. Cellular mechanism of decreased bone in Brtl mouse model of OI: imbalance of decreased osteoblast function and increased osteoclasts and their precursors. J Bone Miner Res. 2008; 23: 1983 – 94.en_US
dc.identifier.citedreferenceMeganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA. Beam hardening artifacts in micro‐computed tomography scanning can be reduced by X‐ray beam filtration and the resulting images can be used to accurately measure BMD. Bone. 2009; 45: 1104 – 16.en_US
dc.identifier.citedreferenceOtsu N. A threshold selection method from gray‐level histograms. IEEE Trans Syst Man Cybern. 1979; 9: 62 – 6.en_US
dc.identifier.citedreferenceHildebrand T, Rüegsegger P. A new method for the model‐independent assessment of thickness in three‐dimensional images. J Microsc. 1997; 185: 67 – 75.en_US
dc.identifier.citedreferenceOliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992; 7: 1565.en_US
dc.identifier.citedreferenceParfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2: 595 – 5610.en_US
dc.identifier.citedreferenceBusa B, Miller LM, Rubin CT, Qin Y‐X, Judex S. Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tissue Int. 2005; 77: 386 – 94.en_US
dc.identifier.citedreferenceDonnelly E, Boskey AL, Baker SP. van der Meulen MCH. Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex. J Biomed Mater Res A. 2010; 92: 1048 – 56.en_US
dc.identifier.citedreferenceVahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y, Nold JB. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1‐34) for 2 years and relevance to human safety. Toxicol Pathol. 2002; 30: 312 – 21.en_US
dc.identifier.citedreferencePapapoulos SE, Cremers SCLM. Prolonged bisphosphonate release after treatment in children. N Engl J Med. 2007; 356: 1075 – 6.en_US
dc.identifier.citedreferenceKomatsubara S, Mori S, Mashiba T, Li J, Nonaka K, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Suppressed bone turnover by long‐term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res. 2004 Jun; 19 ( 6 ): 999 – 1005.en_US
dc.identifier.citedreferenceLi J, Mashiba T, Burr DB. Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. Calcif Tissue Int. 2001; 69: 281 – 6.en_US
dc.identifier.citedreferenceMashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000; 15: 613 – 20.en_US
dc.identifier.citedreferenceMashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001; 28: 524 – 31.en_US
dc.identifier.citedreferenceAllen MR, Reinwald S, Burr DB. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Int. 2008; 82: 354 – 60.en_US
dc.identifier.citedreferenceDavis MS, Kovacic BL, Marini JC, Shih AJ, Kozloff KM. Increased susceptibility to microdamage in Brtl/+ mouse model for osteogenesis imperfecta. Bone. 2012; 50: 784 – 91.en_US
dc.identifier.citedreferenceUveges TE, Kozloff KM, Ty JM, Ledgard F, Raggio CL, Gronowicz G, Goldstein SA, Marini JC. Alendronate treatment of the Brtl osteogenesis imperfecta mouse improves femoral geometry and load response before fracture but decreases predicted material properties and has detrimental effects on osteoblasts and bone formation. J Bone Miner Res. 2009; 24: 849 – 59.en_US
dc.identifier.citedreferenceForlino A, Kuznetsova NV, Marini JC, Leikin S. Selective retention and degradation of molecules with a single mutant [alpha]1(I) chain in the Brtl IV mouse model of OI. Matrix Biol. 2007; 26: 604 – 14.en_US
dc.identifier.citedreferenceReich A, Cabral W, Marini J. Altered transcript pattern during osteoblast differentiation associated with improved bone phenotype in homozygous osteogenesis imperfecta Brtl mice. J Bone Miner Res. 2011; 26 ( Suppl 1).en_US
dc.identifier.citedreferenceMarenzana M, Greenslade K, Eddleston A, Okoye R, Marshall D, Moore A, Robinson MK. Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone. Arthritis Rheum. 2011; 63: 2385 – 95.en_US
dc.identifier.citedreferenceLi X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008; 23: 860 – 9.en_US
dc.identifier.citedreferenceOminsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010; 25: 948 – 59.en_US
dc.identifier.citedreferenceForlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011; 7: 540 – 57.en_US
dc.identifier.citedreferenceSakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2‐year randomised placebo‐controlled study. Lancet. 2004; 363: 1427 – 31.en_US
dc.identifier.citedreferenceGatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tatò L, Viapiana O, Adami S. Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res. 2005; 20: 758 – 63.en_US
dc.identifier.citedreferenceLetocha AD, Cintas HL, Troendle JF, Reynolds JC, Cann CE, Chernoff EJ, Hill SC, Gerber LH, Marini JC. Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short‐term functional improvement. J Bone Miner Res. 2005; 20: 977 – 86.en_US
dc.identifier.citedreferenceRauch F, Munns CF, Land C, Cheung M, Glorieux FH. Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo‐controlled study. J Bone Miner Res. 2009; 24: 1282 – 9.en_US
dc.identifier.citedreferenceWard LM, Rauch F, Whyte MP, D'Astous J, Gates PE, Grogan D, Lester EL, McCall RE, Pressly TA, Sanders JO, Smith PA, Steiner RD, Sullivan E, Tyerman G, Smith‐Wright DL, Verbruggen N, Heyden N, Lombardi A, Glorieux FH. Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo‐controlled study. J Clin Endocrinol Metab. 2011; 96: 355 – 64.en_US
dc.identifier.citedreferenceWhyte MP, McAlister WH, Novack DV, Clements KL, Schoenecker PL, Wenkert D. Bisphosphonate‐induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res. 2008; 23: 1698 – 707.en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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