A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta

Recent studies have reported that bisphosphonates reduce fracture incidence and improve bone density in children with osteogenesis imperfecta (OI). Ho wever, questions still persist concerning the effect of these drugs on bone properties such as ultrastructure and quality, particularly in the growing patient. To address these issues, the third-generation bisphosphonate alen dronate was evaluated in the growing oim/oim mouse. an animal model of mode rate-to-severe OI. Alendronate was administered to 6-week-old mice during a period of active growth at a dosage of 73 mug alendronate/kg/day for the f irst 4 weeks and 26 mug alendronate/kg/day for the next 4 weeks. Positive t reatment effects included a reduction in the number of fractures sustained by the alendronate-treated oim/oim mice compared with untreated oim/oim mic e (2.1 +/- 2.0 vs 3.2 +/- 1.6 fractures per mouse), increased femoral metap hyseal density (0.111 +/- 0.02 vs 0.034 +/- 0.04 g/cm(2)), a tendency towar ds reduced tibial bowing (4.0 +/- 3.7 vs 6.1 +/- 5.8 degrees), and towards increased femoral diameter (1.22 +/- 0.12 vs 1.15 +/- 0.11 mm). Potential n egative effects included a persistence of calcified cartilage in the treate d oim/oim metaphyses compared with treated wildtype (+/+) (33.8 +/- 11.1 vs 22.1 +/- 10.2%), and significantly shorter femora compared with nontreated oim/ oim mice (14.8 +/- 0.67 vs 15.3 +/- 0.37 turn). This preclinical stud y demonstrates that alendronate is effective in reducing fractures in a gro wing mouse model of OI, and is also an important indicator of potential pos itive and negative outcomes of third-generation bisphosphonate therapy in c hildren with OI.