A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta
A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta
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DOI：
10.1007/s002230010045
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发表时间：
2001-08-01
影响因子：
4.2
通讯作者：
Boskey, AL
中科院分区：
文献类型：
--
作者：
Camacho, NP;Raggio, CL;Boskey, AL
最近的研究报告，双膦酸盐降低骨折的发生率，并提高骨密度的儿童骨生成障碍（OI）。然而，关于这些药物对骨特性（如超微结构和质量）的影响，特别是在生长期患者中，仍然存在问题。为了解决这些问题，在生长中的oim/oim小鼠中评价了第三代双膦酸盐阿仑膦酸盐。中度至重度OI的动物模型。在活跃生长期，将阿仑膦酸钠给予6周龄小鼠，前4周剂量为73 μ g阿仑膦酸钠/kg/天，后4周剂量为26 μ g阿仑膦酸钠/kg/天。积极的治疗效果包括与未治疗的oim/oim小鼠相比，阿仑膦酸钠治疗的oim/oim小鼠持续骨折的数量减少（每只小鼠2.1 ± 2.0 vs 3.2 ± 1.6处骨折），股骨干骺端密度增加（0.111 +/- 0.02 vs 0.034 +/- 0.04 g/cm（2）），胫骨弯曲倾向减少（4.0 +/- 3.7 vs 6.1 +/- 5.8度），并朝向股骨直径增加（1.22 +/- 0.12 vs 1.15 +/- 0.11 mm）。潜在的负面影响包括与治疗的野生型（+/+）相比，治疗的oim/oim干骺端的钙化软骨持续存在（33.8 +/- 11.1 vs 22.1 +/- 10.2%），与未治疗的oim/ oim小鼠相比，股骨明显缩短（14.8 +/- 0.67 vs 15.3 +/- 0.37转）。这项临床前研究表明，阿仑膦酸钠在生长中的OI小鼠模型中可有效减少骨折，也是第三代双膦酸盐治疗OI儿童的潜在积极和消极结果的重要指标。
Recent studies have reported that bisphosphonates reduce fracture incidence and improve bone density in children with osteogenesis imperfecta (OI). However, 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 alendronate was evaluated in the growing oim/oim mouse. an animal model of moderate-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 first 4 weeks and 26 mug alendronate/kg/day for the next 4 weeks. Positive treatment effects included a reduction in the number of fractures sustained by the alendronate-treated oim/oim mice compared with untreated oim/oim mice (2.1 +/- 2.0 vs 3.2 +/- 1.6 fractures per mouse), increased femoral metaphyseal density (0.111 +/- 0.02 vs 0.034 +/- 0.04 g/cm(2)), a tendency towards 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 negative effects included a persistence of calcified cartilage in the treated 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 study demonstrates that alendronate is effective in reducing fractures in a growing mouse model of OI, and is also an important indicator of potential positive and negative outcomes of third-generation bisphosphonate therapy in children with OI.