Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.
Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.
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DOI：
10.1007/s00198-011-1742-7
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发表时间：
2012-03
影响因子：
4
通讯作者：
Pleshko, N.
中科院分区：
文献类型：
--
作者：
Bargman, R.;Posham, R.;Boskey, A. L.;DiCarlo, E.;Raggio, C.;Pleshko, N.
我们报告了在成骨不全小鼠模型中从婴儿期到成年早期RANKL抑制（RANK-Fc）与双膦酸盐治疗（ALN）的直接比较。ALN和RANK-Fc通过增加较薄的骨小梁数量，降低骨折发生率的程度与干骺端骨量增加相同。RANKL抑制剂在OI中的潜在治疗获益正在研究中。我们报告了在OI模型（oim/oim小鼠）中从婴儿期到成年早期RANKL抑制（RANK-Fc）与双膦酸盐治疗（阿仑膦酸盐; ALN）的直接比较。2周龄oim/oim、oim/+和野生型（+/+）小鼠接受RANK-Fc 1.5 mg/kg每周两次、ALN 0.21 mg/kg/周或生理盐水（每组n = 12-20）处理12周。ALN和RANK-Fc均降低骨折发生率（9.0 ± 3.0盐水4.4 ± 2.7 ALN，4.3 ± 3.0 RANK-Fc骨折/小鼠）。1个月后，所有给药小鼠的血清TRACP-5 b活性降低至65%，但在用RANK-Fc处死时升高至130-200%。ALN组+/+和oim/oim小鼠的干骺端密度显著增加（p < 0.05），RANK-Fc组+/+小鼠的干骺端密度有增加趋势。治疗期间oim/oim股骨生物力学参数未发生变化。ALN和RANK-Fc均显著增加小梁数量（即oim/oim生理盐水为3.73±0.77 1/mm，ALN为7.93± 0.67，RANK-Fc为7.34±1.38）和小梁厚度降低（即oim/oim生理盐水为0.045 mm ±0.003，ALN为0.034±0.003，RANK-Fc为0.032±0. 002）和所有基因型的分离（即oim/oim生理盐水为0.28±0.08 mm，ALN为0.12±0.010 mm，RANK-Fc为13±0.03 mm）。ALN组骨体积分数（BVF）显著增加，RANK-Fc组BVF有增加的趋势。用双膦酸盐或RANK-Fc治疗oim/oim小鼠导致骨折发生率相似降低，干骺端骨体积通过更薄的骨小梁数量增加而增加。
We report a direct comparison of RANKL inhibition (RANK-Fc) with bisphosphonate treatment (ALN) from infancy through early adulthood in a mouse model of Osteogenesis Imperfecta. Both ALN and RANK-Fc decreased fracture incidence to the same degree with increases in metaphyseal bone volume via increased number of thinner trabeculae. The potential therapeutic benefit of RANKL inhibitors in OI is under investigation. We report a direct comparison of RANKL inhibition (RANK-Fc) with bisphosphonate treatment (alendronate; ALN) from infancy through early adulthood in a model of OI, the oim/oim mouse. Two week old oim/oim, oim/+ and wildtype (+/+) mice were treated with RANK-Fc 1.5 mg/kg twice per week, ALN 0.21 mg/kg/week or saline (n = 12-20 per group) for 12 weeks. ALN and RANK-Fc both decreased fracture incidence (9.0 ± 3.0 saline 4.4 ± 2.7 ALN, 4.3 ± 3.0 RANK-Fc fractures per mouse). Serum TRACP-5b activity decreased to 65% after 1 month in all treated mice, but increased to 130-200% at sacrifice with RANK-Fc. Metaphyseal density was significantly increased with ALN in +/+ and oim/oim mice (p < 0.05) and tended to increase with RANK-Fc in +/+ mice. No changes in oim/oim femur biomechanical parameters occurred with treatment. Both ALN and RANK-Fc significantly increased trabecular number (ie 3.73±0.77 1/mm for oim/oim saline vs 7.93±0.67ALN and 7.34±1.38 RANK-Fc) and decreased trabecular thickness (ie 0.045 mm ±0.003 for oim/oim saline vs 0.034±0.003 ALN and 0.032±0.002RANK-Fc) and separation in all genotypes (ie 0.28±0.08 mm for oim/oim saline vs 0.12±0.010 ALN and 13±0.03 RANK-Fc)., with significant increase in bone volume fraction (BVF) with ALN, and a trend towards increased BVF in RANK-Fc. Treatment of oim/oim mice with either a bisphosphonate or a RANK-Fc causes similar decreases in fracture incidence with increases in metaphyseal bone volume via increased number of thinner trabeculae.
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影响因子：
2.9
作者：
Bargman R;Huang A;Boskey AL;Raggio C;Pleshko N
通讯作者：
Pleshko N
影响因子：
8.2
作者：
Cheung, Moira S.;Glorieux, Francis H.
通讯作者：
Glorieux, Francis H.
影响因子：
6.2
作者：
Gatti, D;Viapiana, O;Adami, S
通讯作者：
Adami, S
影响因子：
3.4
作者：
Madenci, E;Yilmaz, K;Coskun, Y
通讯作者：
Coskun, Y
影响因子：
4.2
作者：
Camacho, NP;Raggio, CL;Boskey, AL
通讯作者：
Boskey, AL