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The Brtl mouse has a glycine substitution in col1a1 and is ideal for modeling the effects of bisphosphonate in classical OI. We treated Brtl and wildtype mice with alendronate (Aln; 0.219 mg\/kg\/wk, SC) for 6 or 12 wk and compared treated and untreated femora of both genotypes. Mutant and wildtype bone had similar responses to Aln treatment. Femoral areal BMD and cortical volumetric BMD increased significantly after 12 wk, but femoral length and growth curves were unaltered. Aln improved Brtl diaphyseal cortical thickness and trabecular number after 6 wk and cross-sectional shape after 12 wk. Mechanically, Aln significantly increased stiffness in wildtype femora and load to fracture in both genotypes after 12 wk. However, predicted material strength and elastic modulus were negatively impacted by 12 wk of Aln in both genotypes, and metaphyseal remnants of mineralized cartilage also increased. Brtl femoral brittleness was unimproved. Brtl osteoclast and osteoblast surface were unchanged by treatment. However, decreased mineral apposition rate and bone formation rate\/bone surface and the flattened morphology of Brtl osteoblasts suggested that Aln impaired osteoblast function and matrix synthesis. We conclude that Aln treatment improves Brtl femoral geometry and load to fracture but decreases bone matrix synthesis and predicted material modulus and strength, with striking retention of mineralized cartilage. Beneficial and detrimental changes appear concomitantly. Limiting cumulative bisphosphonate exposure of OI bone will minimize detrimental effects.<\/jats:p>","DOI":"10.1359\/jbmr.081238","type":"journal-article","created":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T20:01:01Z","timestamp":1230580861000},"page":"849-859","source":"Crossref","is-referenced-by-count":58,"title":["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"],"prefix":"10.1093","volume":"24","author":[{"given":"Thomas E","family":"Uveges","sequence":"first","affiliation":[{"name":"These authors contributed equally to this work and are co-first authors"},{"name":"Current address: Trevigen, Gaithersburg, Maryland, USA"},{"name":"Bone and Extracellular Matrix Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"These authors contributed equally to this work and are co-first authors"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Ty","sequence":"additional","affiliation":[{"name":"Current address: Department of Orthopaedic Surgery, duPont Hospital for Children, Wilmington, Delaware, USA"},{"name":"Bone and Extracellular Matrix Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Ledgard","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen L","family":"Raggio","sequence":"additional","affiliation":[{"name":"Center for Skeletal Dysplasias, Hospital for Special Surgery, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Gronowicz","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan C","family":"Marini","sequence":"additional","affiliation":[{"name":"Bone and Extracellular Matrix Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020320012913300_bib1","volume-title":"Bisphosphonates in Bone Disease","author":"Fleisch","year":"2000"},{"key":"2024020320012913300_bib2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1056\/NEJMc062792","article-title":"Prolonged bisphosphonate release after treatment in children","volume":"356","author":"Papapoulos","year":"2007","journal-title":"N Engl J Med"},{"key":"2024020320012913300_bib3","volume-title":"Nelson Textbook of Pediatrics","author":"Marini","year":"2004","edition":"17th ed"},{"key":"2024020320012913300_bib4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/0471221929.ch8","volume-title":"Connective Tissue and Its Heritable Disorders","author":"Byers","year":"2002","edition":"2nd ed"},{"key":"2024020320012913300_bib5","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0022-3476(97)70074-X","article-title":"Intravenous pamidronate treatment in osteogenesis imperfecta","volume":"131","author":"Bembi","year":"1997","journal-title":"J Pediatr"},{"key":"2024020320012913300_bib6","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1056\/NEJM199810013391402","article-title":"Cyclic administration of pamidronate in children with severe osteogenesis imperfecta","volume":"339","author":"Glorieux","year":"1998","journal-title":"N Engl J Med"},{"key":"2024020320012913300_bib7","first-page":"1846","article-title":"Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age","volume":"85","author":"Plotkin","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020320012913300_bib8","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1297-319X(02)00434-7","article-title":"Effect of cyclical intravenous pamidronate therapy in children with osteogenesis imperfecta. 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